The pro-inflammatory cytokines interleukin 1 (IL-1) and 6 (IL-6) are crucially involved in the regulation of a multitude of physiological processes, in particular coordinating the immune response upon bacterial infection and tissue injury. Both interleukins induce complex signalling cascades and trigger the production of mitogenic, pro-proliferative, anti-apoptotic, chemotactic, and pro-angiogenic factors thereby affecting the delicate balance between regenerationvs. invasive growth, tumourigenesis and metastasis. Moreover, several links to insulin resistance have been found within their associated signalling networks. Focusing on this from a systems biology perspective, we introduce comprehensive large-scale network models of IL-1 and IL-6 signalling which are based on a logical modelling approach and reflect the current biological knowledge. Theoretical network analysis enabled us to uncover general topological features and to make testable predictions on the stimulus-response behaviour of the networks. In this context, non-intuitive network-wide species dependencies as well as structures of regulatory feedback and feed-forward mechanisms could be characterised. By integrating high-throughput phosphoproteomic data from primary human hepatocytes we optimised the model structures to obtain models with high prediction accuracy for hepatocytes. Our model-based data analysis, for instance, suggested model modifications regarding (i) Akt contribution to IL-1-stimulated p38 MAPK activation and (ii) insignificant p38 MAPK activation in response to IL-6. In light of the presented results and in conjunction with the detailed model documentations, both models hold great potential for theoretical studies and practical applications. Helikar Tomas thelika@unmc.edu University of Nebraska - Lincoln 2013-08-26T10:05:13Z 2017-05-18T13:30:40Z

<div><span style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia">Name: Casein Kinase II</font></span></div><span style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia">Heterotetramer composed of two catalytic subunits (alpha chain and/or alpha' chain) and two regulatory subunits (beta chains)</font></span><div><span style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia"><br/></font></span></div><div><span style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia">Alpha Subunits</font></span></div><div><ul><li><font face="Georgia"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Casein kinase II subunit alpha, UniProt ID: </span><span style="background-color: rgb(255, 255, 255);">P68400</span></font></li><li><font face="Georgia"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Casein kinase II subunit alpha', UniProt ID:</span><span style="background-color: rgb(255, 255, 255);">P19784</span></font></li><li><font face="Georgia"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Casein kinase II subunit alpha 3, UniProt ID: </span><span style="background-color: rgb(255, 255, 255);">Q8NEV1</span></font></li></ul></div><div><span style="background-color: rgb(255, 255, 255);"><font face="Georgia"><br/></font></span></div><div><span style="background-color: rgb(255, 255, 255);"><font face="Georgia">Beta Subunit</font></span></div><div><ul><li><font face="Georgia"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Casein kinase II subunit beta, UniProt ID: </span><span style="background-color: rgb(255, 255, 255);">P67870</span></font></li></ul></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Nuclear factor of kappa light polypeptide gene enhancer in B-cells </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">inhibitor</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">, </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">alpha</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P25963" style="text-decoration: none; background-color: rgb(255, 255, 255);">P25963</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/4792" ref="ordinalpos=4&ncbi_uid=4792&link_uid=4792" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">NFKBIA</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">4792</span></font></div><div style="font-size: 10pt; font-family: Arial, Verdana;"><span style="font-family: arial, helvetica, clean, sans-serif; font-size: 13.333333969116211px; line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><br/></span></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2">mTOR complex 2 consists of [1]: </font><div><font face="Georgia" size="2"><br/></font></div><div><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Mechanistic target of rapamycin (serine/threonine kinase)</font></span></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/P42345" style="text-decoration: none; background-color: rgb(255, 255, 255);">P42345</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/2475" ref="ordinalpos=1&ncbi_uid=2475&link_uid=2475" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">MTOR</span></a></font></div><div><font face="Georgia" size="2">Gene ID: 2475</font></div></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">MTOR associated protein, LST8 homolog (S. cerevisiae) [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q9BVC4" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9BVC4</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/64223" ref="ordinalpos=1&ncbi_uid=64223&link_uid=64223" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">MLST8</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">64223</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">proline rich 5 (renal) [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P85299" style="text-decoration: none; background-color: rgb(255, 255, 255);">P85299</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/55615" ref="ordinalpos=8&ncbi_uid=55615&link_uid=55615" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">PRR5</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID:</span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;"> </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">55615</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Mitogen-activated protein kinase associated protein 1 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q9BPZ7" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9BPZ7</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/79109" ref="ordinalpos=7&ncbi_uid=79109&link_uid=79109" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">MAPKAP1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;"> </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">79109</span></font></div><div><div style="line-height: 20.2702693939209px; background-color: rgb(255, 255, 255);"><span style="line-height: 18.88888931274414px;"><font face="Georgia" size="2">Regulatory associated protein of MTOR, complex 1</font></span></div><div style="line-height: 20.2702693939209px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q6R327" style="outline: none; text-decoration: none;">Q6R327</a></font></div><div style="line-height: 20.2702693939209px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/253260" ref="ordinalpos=1&ncbi_uid=253260&link_uid=253260" style="outline: none; line-height: 18.88888931274414px; white-space: nowrap;"><span class="highlight">RICTOR</span></a></font></div><div style="line-height: 20.2702693939209px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: <span style="line-height: 17.77777862548828px;">253260</span></font></div></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">DEP domain containing MTOR-interacting protein [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q8TB45" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q8TB45</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/64798" ref="ordinalpos=1&ncbi_uid=64798&link_uid=64798" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">DEPTOR</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">64798</span></font></div><div style="font-size: 10pt; font-family: Arial, Verdana;"><span style="background-color: rgb(255, 255, 255); color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 12.222222328186035px; line-height: 17.77777862548828px;"><br/></span></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Suppressor of cytokine signaling 1 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/O15524" style="text-decoration: none; background-color: rgb(255, 255, 255);">O15524</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/8651" ref="ordinalpos=1&ncbi_uid=8651&link_uid=8651" style="line-height: 18.88888931274414px; white-space: nowrap;"><span class="highlight">SOCS1</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">8651</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Phosphatase</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> and </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">tensin </span><span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;"></span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">homolog</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P60484" style="text-decoration: none; background-color: rgb(255, 255, 255);">P60484</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name:</span><a href="http://www.ncbi.nlm.nih.gov/gene/5728" ref="ordinalpos=1&ncbi_uid=5728&link_uid=5728" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">PTEN</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;"> </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">5728</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Suppressor of cytokine signaling 3 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/O14543" style="text-decoration: none; background-color: rgb(255, 255, 255);">O14543</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/9021" ref="ordinalpos=1&ncbi_uid=9021&link_uid=9021" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">SOCS3</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">9021</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2">TRAF6-regulated IKK activator 1</font><div><font face="Georgia" size="2">Dimeric E2 enzyme consists of [1]:</font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Ubiquitin-conjugating enzyme E2N [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P61088" style="text-decoration: none; background-color: rgb(255, 255, 255);">P61088</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/7334" ref="ordinalpos=11&ncbi_uid=7334&link_uid=7334" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">UBE2N</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">7334</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Ubiquitin-conjugating enzyme E2 variant 1 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q13404" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q13404</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/7335" ref="ordinalpos=2&ncbi_uid=7335&link_uid=7335" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">UBE2V1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">7335</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2">Inducible negative regulator, restricted to monocytes/macrophages. </font><div style="line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin-1 receptor-associated kinase 3 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><span class="highlight">Homo sapiens</span></em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></div><div style="line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q9Y616" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9Y616</a></font></div><div style="line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/11213" ref="ordinalpos=2&ncbi_uid=11213&link_uid=11213" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IRAK3</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88607406616211px;">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">11213</span></font></div>

2015-11-15T18:45:36Z

<div><font face="Georgia"><span class="RECOMMENDED" style="line-height: 16px; background-color: rgb(255, 255, 255);"><span class="FULL" style="padding-left: 1em;">UniProt ID:</span></span><span style="background-color: rgb(255, 255, 255);">Q8NFZ5<br/></span><span class="RECOMMENDED" style="line-height: 16px; background-color: rgb(255, 255, 255);"><span class="FULL" style="padding-left: 1em;">TNFAIP3-interacting protein 2</span></span></font></div><div class="alternatives" style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia"><acronym class="ALTERNATIVE" title="A synonym of the recommended name." style="border: none; cursor: pointer; font-style: italic;">Alternative name(s):</acronym><br/><span style="padding-left: 1em;"><acronym class="names FULL" style="border: none; cursor: pointer; padding-left: 1em;"></acronym></span><span class="FULL_NAME">A20-binding inhibitor of NF-kappa-B activation 2</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">v-</span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">src</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> avian sarcoma (Schmidt-Ruppin A-2) viral oncogene homolog [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P12931" style="text-decoration: none; background-color: rgb(255, 255, 255);">P12931</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/6714" ref="ordinalpos=1&ncbi_uid=6714&link_uid=6714" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">SRC</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">6714</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2">Short myD88 protein (no intermediary domain, amino acids 110-157)<br/></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Myeloid differentiation primary response 88 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span> </font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q99836" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q99836</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/4615" ref="ordinalpos=1&ncbi_uid=4615&link_uid=4615" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">MYD88</span></a></font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">4615</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase beta [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/O14920" style="text-decoration: none; background-color: rgb(255, 255, 255);">O14920</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3551" ref="ordinalpos=1&ncbi_uid=3551&link_uid=3551" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IKBKB</a></font></div><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 3551</font></span></div><div style="font-size: 10pt; font-family: Arial, Verdana;"><span style="font-family: arial, helvetica, clean, sans-serif; font-size: 13.333333969116211px; line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><br/></span></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2">Soluble IL-RI/II (IL-1R, type I or II) [1]. </font><div><font face="Georgia" size="2"><br/></font><div><font face="Georgia" style="font-size: 13.513513565063477px;"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin 1 receptor</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">, </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">type </span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">I [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div style="font-family: Arial, Verdana; font-size: 13.513513565063477px;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P14778" style="text-decoration: none; background-color: rgb(255, 255, 255);">P14778</a></font></div><div style="font-family: Arial, Verdana; font-size: 13.513513565063477px;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3554" ref="ordinalpos=2&ncbi_uid=3554&link_uid=3554" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL1R1</a></font></div><div style="font-family: Arial, Verdana; font-size: 13.513513565063477px;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;"> </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3554</span></font></div></div><div style="font-family: Arial, Verdana; font-size: 13.513513565063477px;"><font face="Georgia"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin 1 receptor, type II [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P27930" style="text-decoration: none; background-color: rgb(255, 255, 255);">P27930</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/7850" ref="ordinalpos=1&ncbi_uid=7850&link_uid=7850" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">IL1R2</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">7850</span></font></div></div></div>

2017-05-18T12:50:02Z

<div><span style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">3-phosphoinositide-dependent protein kinase 1</font></span></div><font face="Georgia">Uniprot ID: <a href="http://www.uniprot.org/uniprot/Q15118">Q15118</a></font><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/5170" ref="ordinalpos=1&ncbi_uid=5170&link_uid=5170" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">PDPK1</span></a></font></div><div><font face="Georgia" size="2">Gene ID: 5170</font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin-</span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">1</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> receptor-</span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">associated</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">kinase</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">1 </span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">[</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P51617" style="text-decoration: none; background-color: rgb(255, 255, 255);">P51617</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3654" ref="ordinalpos=6&ncbi_uid=3654&link_uid=3654" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IRAK1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3654</span></font></div>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Dummy Species [1]. </span><br/><br/>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Dummy Species [1]. </span>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Nitric oxide synthase</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> 2, </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">inducible </span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">[</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P35228" style="text-decoration: none; background-color: rgb(255, 255, 255);">P35228</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/4843" ref="ordinalpos=3&ncbi_uid=4843&link_uid=4843" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">NOS2</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">4843</span></font></div>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Timescale dummy species [1]. </span>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin 8</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P10145" style="text-decoration: none; background-color: rgb(255, 255, 255);">P10145</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3576" ref="ordinalpos=5&ncbi_uid=3576&link_uid=3576" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL8</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3576</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin 1, beta [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P01584" style="text-decoration: none; background-color: rgb(255, 255, 255);">P01584</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3553" ref="ordinalpos=1&ncbi_uid=3553&link_uid=3553" style="line-height: 18.88888931274414px; white-space: nowrap;"><span class="highlight">IL1B</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3553</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia"><font><font size="2">Reactive oxygen species, such as enzymatic intermediates. </font></font><font size="2">Click <a href="http://www.ncbi.nlm.nih.gov/pccompound/?term=reactive+oxygen+species">here</a> for more examples. </font></font>

2017-05-18T13:30:40Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">ELK4, ETS-domain protein (SRF accessory protein 1) [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P28324" style="text-decoration: none; background-color: rgb(255, 255, 255);">P28324</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/2005" ref="ordinalpos=3&ncbi_uid=2005&link_uid=2005" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">ELK4</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">2005</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin-1 receptor-associated kinase </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">2</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><span class="highlight">Homo sapiens</span></em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/O43187" style="text-decoration: none; background-color: rgb(255, 255, 255);">O43187</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3656" ref="ordinalpos=11&ncbi_uid=3656&link_uid=3656" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IRAK2</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3656</span></font></div>

2015-11-15T18:45:36Z

<div><font face="Georgia" size="2"><span class="RECOMMENDED" style="line-height: 16px; background-color: rgb(255, 255, 255);"><acronym class="RECOMMENDED" title="The name recommended by the UniProt consortium." style="border: none; cursor: pointer;">UniProt ID: </acronym></span><span style="background-color: rgb(255, 255, 255);">P17676<br/></span><span class="RECOMMENDED" style="line-height: 16px; background-color: rgb(255, 255, 255);"><acronym class="RECOMMENDED" title="The name recommended by the UniProt consortium." style="border: none; cursor: pointer; font-style: italic;">Recommended name:</acronym></span></font></div><font face="Georgia" size="2"><span class="RECOMMENDED" style="font-style: normal; line-height: 16px; background-color: rgb(255, 255, 255);"><span class="FULL" style="padding-left: 1em;">CCAAT/enhancer-binding protein beta</span></span><br style="line-height: 16px; background-color: rgb(255, 255, 255);"/><acronym class="names SHORT" title="Abbreviation of the full name or an acronym." style="font-style: normal; border: none; cursor: pointer; padding-left: 1.5em; line-height: 16px; background-color: rgb(255, 255, 255);">Short name=</acronym><span class="SHORT_NAME" style="font-style: normal; background-color: rgb(255, 255, 255);">C/EBP beta</span></font><div><font face="Georgia" size="2"><span class="SHORT_NAME" style="font-style: normal; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/1051" ref="ordinalpos=2&ncbi_uid=1051&link_uid=1051" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">CEBPB</a></font></div><div><span class="SHORT_NAME" style="font-style: normal; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 1051</font></span></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">ZFP36 ring finger protein [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P26651" style="text-decoration: none; background-color: rgb(255, 255, 255);">P26651</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/7538" ref="ordinalpos=3&ncbi_uid=7538&link_uid=7538" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">ZFP36</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">7538</span></font></div>

2015-11-15T18:45:36Z

\r\n \r\n \r\n \r\n <div class="page" title="Page 25">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Complete and/or limited proteasomal\r\ndegradation of p105 [1]. </font></p><font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Nuclear</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">factor</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> of kappa light polypeptide gene enhancer in B-cells 1 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P19838" style="text-decoration: none; background-color: rgb(255, 255, 255);">P19838</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/4790" ref="ordinalpos=6&ncbi_uid=4790&link_uid=4790" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">NFKB1</a></font></div><p><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID:</span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">4790</span> </font></p>\r\n </div>\r\n </div>\r\n </div>

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<div><font face="Georgia"><span style="font-size: 13.333333969116211px; line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Activating transcription factor 2 [</span><em style="font-size: 13.333333969116211px; line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="font-size: 13.333333969116211px; line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">(human)]</span></font></div><div><font face="Georgia">Uniprot ID: <a href="http://www.uniprot.org/uniprot/P15336" style="font-size: small; text-decoration: none; background-color: rgb(255, 255, 255);">P15336</a></font></div><div><font face="Georgia">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/1386" ref="ordinalpos=1&ncbi_uid=1386&link_uid=1386" style="font-size: 13.333333969116211px; line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">ATF2</span></a></font></div><div><font face="Georgia">NCBI Gene ID: <span style="background-color: rgb(255, 255, 255); font-size: 12.222222328186035px; line-height: 17.999801635742188px;">1386</span></font></div>

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<span style="font-family: Georgia; font-size: small;">Canonical heterotrimeric NEMO-containing IKKB kinase (IKK) complexes [1]. </span>

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<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Lipopolysaccharide </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">binding protein</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P18428" style="text-decoration: none; background-color: rgb(255, 255, 255);">P18428</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3929" ref="ordinalpos=2&ncbi_uid=3929&link_uid=3929" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">LBP</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3929</span></font></div>

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soluble IL-1R accessory protein

Gene Name: IL1RAP

Uniprot ID: Q9NPH3

Gene ID: 3556

2017-05-18T12:50:02Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Inhibitor of kappa light polypeptide gene enhancer in B-cells, kinase gamma [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q9Y6K9" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9Y6K9</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/8517" ref="ordinalpos=4&ncbi_uid=8517&link_uid=8517" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IKBKG</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">8517</span></font></div>

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Cytosolic p38-mitogen activated protein kinase (MAPK)<div><acronym class="RECOMMENDED" title="The name recommended by the UniProt consortium." style="border: none; cursor: pointer; font-style: italic; font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);">Recommended name:</acronym><br style="font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"/><span class="FULL" style="padding-left: 1em; font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);">Mitogen-activated protein kinase 14</span></div><div><span class="FULL" style="padding-left: 1em; font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"><br/></span></div><div><span class="FULL" style="padding-left: 1em; font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);">UniProt ID:</span><span style="font-family: sans-serif; font-size: 16px; background-color: rgb(255, 255, 255);">Q16539</span></div>

2015-11-15T18:45:36Z

<div><font face="Georgia" size="2"><acronym class="RECOMMENDED" title="The name recommended by the UniProt consortium." style="border: none; cursor: pointer; line-height: 16px; background-color: rgb(255, 255, 255);">UniProt ID:</acronym><acronym class="RECOMMENDED" title="The name recommended by the UniProt consortium." style="font-style: italic; border: none; cursor: pointer; line-height: 16px; background-color: rgb(255, 255, 255);"> </acronym><span style="font-style: normal; background-color: rgb(255, 255, 255);">P01100<br/></span><acronym class="RECOMMENDED" title="The name recommended by the UniProt consortium." style="font-style: italic; border: none; cursor: pointer; line-height: 16px; background-color: rgb(255, 255, 255);">Recommended name:</acronym></font></div><span class="FULL" style="font-style: normal; padding-left: 1em; line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Proto-oncogene c-Fos</font></span><div><font face="Georgia" size="2"><span class="FULL" style="font-style: normal; padding-left: 1em; line-height: 16px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/2353" ref="ordinalpos=5&ncbi_uid=2353&link_uid=2353" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">FOS</a><span style="background-color: rgb(255, 255, 255); line-height: 16px;"> </span></font></div><div><span class="FULL" style="font-style: normal; padding-left: 1em; line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 2353</font></span></div>

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<font face="Georgia" size="2">Heterotrimeric Il-1R signalling complex with cytoplasmic TIR domains [1].</font><div><font face="Georgia" size="2">Composed of: </font></div><div><font face="Georgia" size="2">Il-1 (alpha or beta)</font></div><div><div style="line-height: 20.2702693939209px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px;">Il-1 a</span></font></div><div style="line-height: 20.2702693939209px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px;">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P01583" style="outline: none; text-decoration: none;">P01583</a></font></div><div style="line-height: 20.2702693939209px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px;">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3552" ref="ordinalpos=1&ncbi_uid=3552&link_uid=3552" style="outline: none; line-height: 18.88888931274414px; white-space: nowrap;"><span class="highlight">IL1A</span></a></font></div><div style="line-height: 20.2702693939209px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px;">Gene ID: </span><span style="line-height: 17.77777862548828px;">3552</span></font></div></div><div style="line-height: 20.2702693939209px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><span style="line-height: 17.77777862548828px;">Il-1b</span></font></div><div style="line-height: 20.2702693939209px; background-color: rgb(255, 255, 255);"><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px;">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P01584" style="outline: none; text-decoration: none;">P01584</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px;">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3553" ref="ordinalpos=1&ncbi_uid=3553&link_uid=3553" style="outline: none; line-height: 18.88888931274414px; white-space: nowrap;"><span class="highlight">IL1B</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px;">Gene ID: </span><span style="line-height: 17.77777862548828px;">3553</span></font></div></div><div><font face="Georgia" size="2">Il-1R1</font></div><div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P14778" style="text-decoration: none; background-color: rgb(255, 255, 255);">P14778</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3554" ref="ordinalpos=2&ncbi_uid=3554&link_uid=3554" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL1R1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;"> </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3554</span></font></div></div><div><font face="Georgia" size="2">Il-1RAcP</font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q9NPH3" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9NPH3</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/3556" ref="ordinalpos=2&ncbi_uid=3556&link_uid=3556" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL1RAP</a></font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3556</span></font></div>

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<span style="font-family: Georgia; font-size: small;">Dummy Species [1]. </span>

2015-11-15T18:45:36Z

<font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);"><span style="line-height: 18.88888931274414px;">Mitogen-activated protein kinase kinase kinase 14 [</span><em style="line-height: 18.88888931274414px;">Homo sapiens</em><span style="line-height: 18.88888931274414px;">(human)]</span></font><div><font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);"><span style="line-height: 18.88888931274414px;">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q99558" style="text-decoration: none;">Q99558</a></font></div><div><font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);"><span style="line-height: 18.88888931274414px;">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/9020" ref="ordinalpos=3&ncbi_uid=9020&link_uid=9020" style="line-height: 18.88888931274414px; white-space: nowrap;">MAP3K14</a></font></div><div><font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);"><span style="line-height: 18.88888931274414px;">Gene ID:</span><span style="line-height: 17.77777862548828px;">9020</span></font></div>

2015-11-15T18:45:36Z

<span style="font-style: normal;">Jun proto-oncogene (</span><em>Homo sapiens)</em><div>NCBI Gene ID: 3725</div>

2015-11-15T18:45:36Z

\r\n \r\n \r\n <div class="page" title="Page 25">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia"><font size="2">Noncanonical NF-KB pathway where </font><span style="font-size: 10pt;">p52-RelB heterodimers activate the NF-KB pathway</span><span style="font-size: small;"> [1]. </span></font></p>\r\n </div>\r\n </div>\r\n </div>

2015-11-15T18:45:36Z

<div><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);"><span style="line-height: 17px;"><font face="Georgia" size="2">Phosphatidylinositol Triphosphate</font></span></span></div><div><font face="Georgia" size="2"><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);"><span style="line-height: 17px;">PubChem ID:</span></span><span style="line-height: 19px; background-color: rgb(255, 255, 255);"> </span><a name="cid2entrez" href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pccompound&term=53480352[uid]" style="border: 0px; outline: 0px; line-height: 19px; vertical-align: baseline; margin: 0px; padding: 0px; text-decoration: none; background-color: rgb(255, 255, 255);">53480352<br/></a><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Formula:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> C</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">47</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">H</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">86</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">O</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">22</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">P</span><sub style="border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">4</sub><span style="line-height: 17px; background-color: rgb(255, 255, 255);">   </span><span style="border: 0px; outline: 0px; line-height: 17px; vertical-align: baseline; margin: 0px; padding: 0px; background-color: rgb(255, 255, 255);">Molecular Weight:</span><span style="line-height: 17px; background-color: rgb(255, 255, 255);"> 1127.067588 </span></font></div><div style="font-weight: normal; font-size: 10pt; font-family: Arial, Verdana;"><span style="color: rgb(85, 85, 85); font-family: Arial, Verdana, sans-serif; font-size: 13px; line-height: 17px; background-color: rgb(255, 255, 255);"><br/></span></div>

2015-11-15T18:45:36Z

<font face="Georgia"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Nuclear</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">factor</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> of kappa light polypeptide gene enhancer in B-cells 1 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P19838" style="text-decoration: none; background-color: rgb(255, 255, 255);">P19838</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/4790" ref="ordinalpos=6&ncbi_uid=4790&link_uid=4790" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">NFKB1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID:</span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">4790</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">TNF receptor-associated factor 6, E3 ubiquitin protein ligase [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q9Y4K3" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9Y4K3</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/7189" ref="ordinalpos=1&ncbi_uid=7189&link_uid=7189" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">TRAF6</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">7189</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Mitogen-activated protein kinase kinase 1 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q02750" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q02750</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/5604" ref="ordinalpos=12&ncbi_uid=5604&link_uid=5604" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">MAP2K1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">5604</span></font></div>

2015-11-15T18:45:36Z

\r\n \r\n \r\n <div class="page" title="Page 22">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Noncanonical homodimeric IKKa complex [1].</font></p>\r\n </div>\r\n </div>\r\n </div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">v-rel avian reticuloendotheliosis viral oncogene homolog A [</span><em style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q04206" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q04206</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/5970" ref="ordinalpos=1&ncbi_uid=5970&link_uid=5970" style="line-height: 17.999801635742188px; white-space: nowrap; background-color: rgb(255, 255, 255);">RELA</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 16.19982147216797px;">5970</span></font></div>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Timescale dummy species [1]. </span>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Ribosomal protein S6 kinase, 90kDa, polypeptide 5 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID:</span><a href="http://www.uniprot.org/uniprot/O75582" style="text-decoration: none; background-color: rgb(255, 255, 255);">O75582</a><span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;"> </span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/9252" ref="ordinalpos=6&ncbi_uid=9252&link_uid=9252" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">RPS6KA5</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">9252</span></font></div>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Dummy Species [1]. </span>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Hepatocyte</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">nuclear</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">factor</span><span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;"></span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">4</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">, </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">alpha</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P41235" style="text-decoration: none; background-color: rgb(255, 255, 255);">P41235</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3172" ref="ordinalpos=2&ncbi_uid=3172&link_uid=3172" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">HNF4A</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3172</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2">Heat Shock Protein 27</font><div><font face="Georgia" size="2">Serine-phosphorylated oliomeric phosphoprotein [1]</font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/P04792" style="text-decoration: none; background-color: rgb(255, 255, 255);">P04792</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/3315" ref="ordinalpos=15&ncbi_uid=3315&link_uid=3315" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">HSPB1</a></font></div><div><font face="Georgia" size="2">Gene ID: 3315</font></div><div style="font-size: 10pt;"><font face="ArialMT"><br/></font></div>

2015-11-15T18:45:36Z

\r\n \r\n \r\n <div class="page" title="Page 21">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Activated (canonical) IKK complex; attributable\r\nto catalytic IKKa activity [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2">Inactive HGF precursor</font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Hepatocyte growth factor (hepapoietin A; scatter factor) [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P14210" style="text-decoration: none; background-color: rgb(255, 255, 255);">P14210</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3082" ref="ordinalpos=1&ncbi_uid=3082&link_uid=3082" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">HGF</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3082</span></font></div>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Timescale dummy species [1]. </span>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Timescale dummy species [1]. </span>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin 6</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (interferon, beta 2) [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P05231" style="text-decoration: none; background-color: rgb(255, 255, 255);">P05231</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3569" ref="ordinalpos=2&ncbi_uid=3569&link_uid=3569" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL6</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3569</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Serum amyloid A1 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88607406616211px;">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P0DJI8" style="text-decoration: none; background-color: rgb(255, 255, 255);">P0DJI8</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88607406616211px;">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/6288" ref="ordinalpos=9&ncbi_uid=6288&link_uid=6288" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">SAA1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88607406616211px;">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">6288</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin-1 receptor-associated kinase </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">4 </span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">[</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><span class="highlight">Homo sapiens</span></em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q9NWZ3" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9NWZ3</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/51135" ref="ordinalpos=4&ncbi_uid=51135&link_uid=51135" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IRAK4</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">51135</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Tumor progression locus-2 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID:</span><a href="http://www.uniprot.org/uniprot/P41279" style="text-decoration: none; background-color: rgb(255, 255, 255);">P41279</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/8040" ref="ordinalpos=1&ncbi_uid=8040&link_uid=8040" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">TPL2</span></a></font></div><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 8040</font></span></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Toll interacting protein [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q9H0E2" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9H0E2</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/54472" ref="ordinalpos=1&ncbi_uid=54472&link_uid=54472" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">TOLLIP</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">54472</span></font></div>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Dummy Species [1]. </span>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Mitogen-activated protein kinase kinase 4 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P45985" style="text-decoration: none; background-color: rgb(255, 255, 255);">P45985</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/6416" ref="ordinalpos=1&ncbi_uid=6416&link_uid=6416" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">MAP2K4</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">6416</span></font></div>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Dummy Species [1]. </span>

2015-11-15T18:45:36Z

<font face="Georgia" size="2">UniProt ID: <span style="background-color: rgb(255, 255, 255);">P49716</span></font><div><font face="Georgia" size="2"><span class="RECOMMENDED" style="line-height: 16px; background-color: rgb(255, 255, 255);"><acronym class="RECOMMENDED" title="The name recommended by the UniProt consortium." style="border: none; cursor: pointer; font-style: italic;">Recommended name:</acronym><br/><span class="FULL" style="padding-left: 1em;">CCAAT/enhancer-binding protein delta</span></span><br style="line-height: 16px; background-color: rgb(255, 255, 255);"/><acronym class="names SHORT" title="Abbreviation of the full name or an acronym." style="border: none; cursor: pointer; padding-left: 1.5em; line-height: 16px; background-color: rgb(255, 255, 255);">Short name=</acronym><span class="SHORT_NAME" style="background-color: rgb(255, 255, 255);">C/EBP delta</span></font><div class="alternatives" style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><acronym class="ALTERNATIVE" title="A synonym of the recommended name." style="border: none; cursor: pointer; font-style: italic;">Alternative name(s):</acronym><br/><span style="padding-left: 1em;"><acronym class="names FULL" style="border: none; cursor: pointer; padding-left: 1em;"></acronym></span><span class="FULL_NAME">Nuclear factor NF-IL6-beta</span></font></div></div><div class="alternatives" style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/1052" ref="ordinalpos=2&ncbi_uid=1052&link_uid=1052" style="color: rgb(100, 42, 143); line-height: 19.999780654907227px; white-space: nowrap;">CEBPD</a></font></div><div class="alternatives" style="line-height: 16px; background-color: rgb(255, 255, 255);"><span class="FULL_NAME"><font face="Georgia" size="2">Gene ID: 1052</font></span></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Mitogen-activated protein kinase kinase 6 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P52564" style="text-decoration: none; background-color: rgb(255, 255, 255);">P52564</a><span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;"> </span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/5608" ref="ordinalpos=1&ncbi_uid=5608&link_uid=5608" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">MAP2K6</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">5608</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2">Pre-associated TAK1:TAB1:TAB2/3 complex [1]:</font><div style="line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Nuclear receptor subfamily 2, group C, member 2 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></div><div style="line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P49116" style="text-decoration: none; background-color: rgb(255, 255, 255);">P49116</a></font></div><div style="line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/7182" ref="ordinalpos=7&ncbi_uid=7182&link_uid=7182" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">NR2C2</a></font></div><div style="line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">7182</span></font></div><div style="line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">TGF-beta activated kinase 1/MAP3K7 binding protein 1 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></div><div style="line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID:</span><a href="http://www.uniprot.org/uniprot/Q15750" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q15750</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88607406616211px;">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/10454" ref="ordinalpos=1&ncbi_uid=10454&link_uid=10454" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">TAB1</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88607406616211px;">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">10454</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">TGF-beta activated kinase 1/MAP3K7 binding protein 2 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88607406616211px;">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q9NYJ8" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9NYJ8</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88607406616211px;">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/23118" ref="ordinalpos=1&ncbi_uid=23118&link_uid=23118" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">TAB2</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88607406616211px;">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">23118</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">TGF-beta activated kinase 1/MAP3K7 binding protein 3 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></div><div><font face="Georgia" size="2"><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q8N5C8" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q8N5C8</a></font></div><div><font face="Georgia" size="2"><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/257397" ref="ordinalpos=1&ncbi_uid=257397&link_uid=257397" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">TAB3</span></a></font></div><div><font face="Georgia" size="2"><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">257397</span></font></div>

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<div><font face="Georgia"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Ubiquinated TNF receptor-associated factor 6 [1].</span></font></div><font face="Georgia"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">TNF receptor-associated factor 6, E3 ubiquitin protein ligase [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q9Y4K3" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9Y4K3</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/7189" ref="ordinalpos=1&ncbi_uid=7189&link_uid=7189" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">TRAF6</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">7189</span></font></div>

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<font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);">For this model, erk 1 is not differentiated from erk2. This node therefore represents either erk 1 or erk 2 [1]. </font><div><font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);"><br/></font></div><div><font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);">Mitogen-activated protein kinase 3</font></div><div><font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);">UniProt ID: <a href="http://www.uniprot.org/uniprot/P27361" style="text-decoration: none;">P27361</a></font></div><div><font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/5595" ref="ordinalpos=4&ncbi_uid=5595&link_uid=5595" style="line-height: 18.88888931274414px; white-space: nowrap;">MAPK3</a></font></div><div><font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);">Gene ID: 5595</font></div><div><font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);"><br/></font></div><div><font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);">Mitogen-activated protein kinase 1</font></div><div><font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);">UniProt ID:<a href="http://www.uniprot.org/uniprot/P28482" style="text-decoration: none;">P28482</a></font></div><div><font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/5594" ref="ordinalpos=1&ncbi_uid=5594&link_uid=5594" style="line-height: 18.88888931274414px; white-space: nowrap;">MAPK1</a></font></div><div><font face="Georgia" size="2" style="background-color: rgb(255, 255, 255);">Gene ID: 5594</font></div><div style="font-size: 10pt; font-family: Arial, Verdana; font-weight: normal;"><font face="Georgia" size="2"><br/></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2">Alternative splice pattern of IRAK1. Found predominant form of IRAK1 expressed in the brain, inducible in monocytes and dendritic cells, kinase-dead, dominant-negative protein, cannot be phosphorylated by IRAK4 due to a lack of IRAK4 phosphorylation site [1]. </font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin-</span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">1</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> receptor-</span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">associated</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">kinase</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">1 </span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">[</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P51617" style="text-decoration: none; background-color: rgb(255, 255, 255);">P51617</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3654" ref="ordinalpos=6&ncbi_uid=3654&link_uid=3654" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IRAK1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3654</span></font></div></div><div style="font-size: 10pt; font-family: Arial, Verdana;"><br/></div>

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<font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Insulin receptor</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">substrate </span><span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;"></span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">1</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)] </span>serine and threonine-phosphorylated [1].</font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P35568" style="text-decoration: none; background-color: rgb(255, 255, 255);">P35568</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3667" ref="ordinalpos=2&ncbi_uid=3667&link_uid=3667" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IRS1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3667</span></font></div>

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\r\n \r\n \r\n <div class="page" title="Page 25">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">p50 precursor and IKB with C-terminal ankyrin\r\nrepeats [1]. </font></p><p><font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Nuclear</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">factor</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> of kappa light polypeptide gene enhancer in B-cells 1 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></p><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P19838" style="text-decoration: none; background-color: rgb(255, 255, 255);">P19838</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/4790" ref="ordinalpos=6&ncbi_uid=4790&link_uid=4790" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">NFKB1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID:</span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">4790</span></font></div><p style="font-size: 10pt; font-family: Arial, Verdana;"><span style="font-size: 10.000000pt; font-family: 'ArialMT'"> </span></p>\r\n </div>\r\n </div>\r\n </div>

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<span style="font-family: Georgia; font-size: small;">Timescale dummy species [1]. </span>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Dummy Species [1]. </span>

2015-11-15T18:45:36Z

<span style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia">AN1-type zinc finger protein 5</font></span><div><font face="Georgia"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">UniProt ID: </span><span style="background-color: rgb(255, 255, 255);">O76080</span></font></div><div><span style="background-color: rgb(255, 255, 255);"><font face="Georgia"><br/></font></span></div><div><font face="Georgia"><span style="background-color: rgb(255, 255, 255);">alternative names:</span><span style="background-color: rgb(255, 255, 255); line-height: 16px;">Zinc finger A20 domain-containing protein 2</span></font></div><div style="font-size: 10pt; font-family: Arial, Verdana;"><br/></div>

2015-11-15T18:45:36Z

<span class="RECOMMENDED" style="font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"><acronym class="RECOMMENDED" title="The name recommended by the UniProt consortium." style="border: none; cursor: pointer; font-style: italic;">Recommended name:</acronym><br/><span class="FULL" style="padding-left: 1em;">Prostaglandin G/H synthase 2</span></span><br style="font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"/><acronym class="names EC" title="Enzyme Commission number." style="border: none; cursor: pointer; padding-left: 1.5em; font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);">EC=</acronym><span class="EC_NAME" style="font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"><a href="http://enzyme.expasy.org/EC/1.14.99.1" style="text-decoration: none;">1.14.99.1</a></span><div class="alternatives" style="font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"><acronym class="ALTERNATIVE" title="A synonym of the recommended name." style="border: none; cursor: pointer; font-style: italic;">Alternative name(s):</acronym><br/><acronym class="names FULL" style="border: none; cursor: pointer; padding-left: 1em;"></acronym><span class="FULL_NAME">Cyclooxygenase-2</span></div><div class="alternatives" style="font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"><span class="FULL_NAME"><br/></span></div><div class="alternatives" style="font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"><span class="FULL_NAME">UniProt ID: </span><span style="line-height: normal; font-size: 16px;">P35354</span></div>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Dummy Species [1]. </span>

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<span style="font-family: Georgia; font-size: small;">Timescale dummy species [1]. </span>

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<div><font face="Georgia" size="2"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">Chemokine (C-C motif) ligand 2 [</span><em style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">(human)]</span></font></div><div><font face="Georgia" size="2"><span style="background-color: rgb(255, 255, 255);">UniProt ID: P13500</span><span style="background-color: rgb(255, 255, 255);"> </span></font></div><div><font face="Georgia" size="2"><span style="background-color: rgb(255, 255, 255);">Gene Name: </span><span class="highlight" style="line-height: 17.999801635742188px; white-space: nowrap; background-color: rgb(255, 255, 255);"><a href="http://www.ncbi.nlm.nih.gov/gene/6347" ref="ordinalpos=1&ncbi_uid=6347&link_uid=6347" style="line-height: 17.999801635742188px; white-space: nowrap; background-color: rgb(255, 255, 255);">CCL2</a></span></font></div><div><font face="Georgia" size="2">Gene ID: 6347</font></div><div><br/></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2">NALP-inflammasome consists of [1,2</font><span style="font-family: Georgia; font-size: small;">]: </span><div><div><font face="Georgia" size="2"><br/></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Caspase 1, apoptosis-related cysteine peptidase [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P29466" style="text-decoration: none; background-color: rgb(255, 255, 255);">P29466</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/834" ref="ordinalpos=2&ncbi_uid=834&link_uid=834" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">CASP1</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">834</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Caspase 5, apoptosis-related cysteine peptidase [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></div><div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P51878" style="text-decoration: none; background-color: rgb(255, 255, 255);">P51878</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/838" ref="ordinalpos=1&ncbi_uid=838&link_uid=838" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">CASP5</span></a></font></div><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 838</font></span></div></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">PYD and CARD domain containing [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font></div><div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q9ULZ3" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9ULZ3</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/29108" ref="ordinalpos=1&ncbi_uid=29108&link_uid=29108" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">PYCARD</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">29108</span></font></div></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">NLR family, pyrin domain containing </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">3</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></div><div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q96P20" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q96P20</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/114548" ref="ordinalpos=1&ncbi_uid=114548&link_uid=114548" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">NLRP3</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">114548</span></font></div></div></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">KH-type</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">splicing</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">regulatory</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> protein [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q92945" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q92945</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/8570" ref="ordinalpos=1&ncbi_uid=8570&link_uid=8570" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">KHSRP</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">8570</span></font></div>

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<span style="font-family: Georgia; font-size: small;">Dummy Species [1]. </span>

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\r\n \r\n \r\n <div class="page" title="Page 21">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Incomplete IKBA phosphorylation and\r\nsubsequent inhibitor dissociation without degradation [1].  </font></p>\r\n </div>\r\n </div>\r\n </div>

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<sup><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Myeloid differentiation primary response 88 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font></sup><div><sup><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q99836" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q99836</a></font></sup></div><div><sup><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/4615" ref="ordinalpos=1&ncbi_uid=4615&link_uid=4615" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">MYD88</span></a></font></sup></div><div><sup><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">4615</span></font></sup></div><div style="font-size: 10pt; font-family: Arial, Verdana;"><span style="font-family: arial, helvetica, clean, sans-serif; font-size: 13.333333969116211px; line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><br/></span></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2">TPL2 proteolysis/degradation [1]. </font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Tumor progression locus-2 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID:</span><a href="http://www.uniprot.org/uniprot/P41279" style="text-decoration: none; background-color: rgb(255, 255, 255);">P41279</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/8040" ref="ordinalpos=1&ncbi_uid=8040&link_uid=8040" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">TPL2</span></a></font></div><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 8040</font></span></div></div>

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<div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Inactive cytoplasmic IL-1 beta precursor</span></font></div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin 1, beta [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P01584" style="text-decoration: none; background-color: rgb(255, 255, 255);">P01584</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3553" ref="ordinalpos=1&ncbi_uid=3553&link_uid=3553" style="line-height: 18.88888931274414px; white-space: nowrap;"><span class="highlight">IL1B</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3553</span></font></div>

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<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Mitogen-activated protein kinase kinase kinase 3 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q99759" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q99759</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name</span><span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;">: </span><a href="http://www.ncbi.nlm.nih.gov/gene/4215" ref="ordinalpos=3&ncbi_uid=4215&link_uid=4215" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">MAP3K3</a><span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;"> </span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">4215</span></font></div>

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<span style="font-family: Georgia; font-size: small;">Dummy Species [1]. </span>

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<div><font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Phosphatidylinositol</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">-4,5-bisphosphate 3-kinase, catalytic subunit alpha [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P42336" style="text-decoration: none; background-color: rgb(255, 255, 255);">P42336</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/5290" ref="ordinalpos=1&ncbi_uid=5290&link_uid=5290" style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px; white-space: nowrap;">PIK3CA</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">5290</span></font></div>

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<font face="Georgia" size="2">Dummy Species [1]. </font>

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<font face="Georgia" size="2">3 established mammalian homologues [1]. </font><div><font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Pellino</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> E3 ubiquitin protein ligase 1 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q96FA3" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q96FA3</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/57162" ref="ordinalpos=2&ncbi_uid=57162&link_uid=57162" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">PELI1</a></font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">57162</span></font></div><div><div><font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Pellino</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> E3 ubiquitin protein ligase family member 2 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q9HAT8" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9HAT8</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/57161" ref="ordinalpos=3&ncbi_uid=57161&link_uid=57161" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">PELI2</a></font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">57161</span></font></div></div><div><div><font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Pellino</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> E3 ubiquitin protein ligase family member 3 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q8N2H9" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q8N2H9</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/246330" ref="ordinalpos=5&ncbi_uid=246330&link_uid=246330" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">PELI3</a></font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;"> </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">246330</span></font></div></div><div style="font-size: 10pt; font-family: Arial, Verdana;"><br/></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Plasminogen activator, urokinase receptor [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span><br/></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P00749" style="text-decoration: none; background-color: rgb(255, 255, 255);">P00749</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/5329" ref="ordinalpos=8&ncbi_uid=5329&link_uid=5329" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">PLAUR</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;"> </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">5329</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Glycogen synthase kinase 3</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font><div><font face="Georgia" size="2">?/? (species refers to both currently known isoforms) <br/></font><div><font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Glycogen synthase kinase 3 </span>?</font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P49841" style="text-decoration: none; background-color: rgb(255, 255, 255);">P49841</a></font><div><div style="line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/2932" ref="ordinalpos=1&ncbi_uid=2932&link_uid=2932" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">GSK3B</a></font></div><div style="line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">2932</span></font></div></div></div></div><div style="line-height: normal;"><font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Glycogen synthase kinase 3</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span>?</font></div><div style="line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P49840" style="text-decoration: none; background-color: rgb(255, 255, 255);">P49840</a></font><div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/2931" ref="ordinalpos=4&ncbi_uid=2931&link_uid=2931" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">GSK3A</a></font></div><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 2931</font></span></div></div></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin 1 </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">receptor </span><span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;"></span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">antagonist</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P14778" style="text-decoration: none; background-color: rgb(255, 255, 255);">P14778</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3557" ref="ordinalpos=1&ncbi_uid=3557&link_uid=3557" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL1RN</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3557</span></font></div>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Timescale dummy species [1]. </span>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Dummy Species [1]. </span>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Canonical heterotrimeric NEMO-containing IKKB kinase (IKK) complexes [1]. </span>

2015-11-15T18:45:36Z

\r\n \r\n \r\n <div class="page" title="Page 22">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Newly synthesised IL-1b [1]. </font></p><p><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin 1, beta [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></p><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P01584" style="text-decoration: none; background-color: rgb(255, 255, 255);">P01584</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3553" ref="ordinalpos=1&ncbi_uid=3553&link_uid=3553" style="line-height: 18.88888931274414px; white-space: nowrap;"><span class="highlight">IL1B</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3553</span></font></div>\r\n </div>\r\n </div>\r\n </div>

2015-11-15T18:45:36Z

<font size="2" face="Georgia">Referring to p65(RelA):p50\r\nheterodimers in this context [1]. </font><div style="font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Nuclear</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">factor</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> of kappa light polypeptide gene enhancer in B-cells 1 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P19838" style="text-decoration: none; background-color: rgb(255, 255, 255);">P19838</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/4790" ref="ordinalpos=6&ncbi_uid=4790&link_uid=4790" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">NFKB1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID:</span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">4790</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">v-rel avian reticuloendotheliosis viral oncogene homolog A [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q04206" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q04206</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/5970" ref="ordinalpos=1&ncbi_uid=5970&link_uid=5970" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">RELA</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID:</span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">5970</span></font></div></div>

2017-05-18T13:30:40Z

\r\n \r\n \r\n \r\n <div class="page" title="Page 23">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Ubiquitinated IRAK1 [1].  </font></p><p><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin-</span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">1</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> receptor-</span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">associated</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">kinase</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">1 </span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">[</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font></p><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P51617" style="text-decoration: none; background-color: rgb(255, 255, 255);">P51617</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3654" ref="ordinalpos=6&ncbi_uid=3654&link_uid=3654" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IRAK1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3654</span></font></div>\r\n </div>\r\n </div>\r\n </div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Mitogen-activated protein kinase-activated protein kinase 2 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88607406616211px;">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P49137" style="text-decoration: none; background-color: rgb(255, 255, 255);">P49137</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88607406616211px;">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/9261" ref="ordinalpos=2&ncbi_uid=9261&link_uid=9261" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">MAPKAPK2</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88607406616211px;">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">9261</span></font></div>

2015-11-15T18:45:36Z

Sub unit of homo- or heterodimer protein: Ap1<div><br/><div>UniProt ID: <span style="font-family: sans-serif; font-size: 16px; background-color: rgb(255, 255, 255);">P05412</span></div><div><span class="RECOMMENDED" style="font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"><acronym class="RECOMMENDED" title="The name recommended by the UniProt consortium." style="border: none; cursor: pointer; font-style: italic;">Recommended name:</acronym><br/><span class="FULL" style="padding-left: 1em;">Transcription factor AP-1</span></span><div class="alternatives" style="font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"><acronym class="ALTERNATIVE" title="A synonym of the recommended name." style="border: none; cursor: pointer; font-style: italic;">Alternative name(s):</acronym><br/><span style="padding-left: 1em;"><acronym class="names FULL" style="border: none; cursor: pointer; padding-left: 1em;"></acronym></span><span class="FULL_NAME">Activator protein 1</span><br/><acronym class="names SHORT" title="Abbreviation of the full name or an acronym." style="border: none; cursor: pointer; padding-left: 2em; font-size: smaller;">Short name=</acronym><span class="SHORT_NAME" style="font-size: smaller;">AP1</span><br/><span style="padding-left: 1em;"><acronym class="names FULL" style="border: none; cursor: pointer; padding-left: 1em;"></acronym></span><span class="FULL_NAME">Proto-oncogene c-Jun</span></div></div></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin 1 receptor, type II [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P27930" style="text-decoration: none; background-color: rgb(255, 255, 255);">P27930</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/7850" ref="ordinalpos=1&ncbi_uid=7850&link_uid=7850" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">IL1R2</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">7850</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin 1 receptor</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">, </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">type </span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">I [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P14778" style="text-decoration: none; background-color: rgb(255, 255, 255);">P14778</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3554" ref="ordinalpos=2&ncbi_uid=3554&link_uid=3554" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL1R1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;"> </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3554</span></font></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Interleukin 1, alpha [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P01583" style="text-decoration: none; background-color: rgb(255, 255, 255);">P01583</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3552" ref="ordinalpos=1&ncbi_uid=3552&link_uid=3552" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">IL1A</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3552</span></font></div>

2015-11-15T18:45:36Z

<span style="font-family: Georgia; font-size: small;">Dummy Species [1]. </span>

2015-11-15T18:45:36Z

<div><span class="RECOMMENDED" style="font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"><acronym class="RECOMMENDED" title="The name recommended by the UniProt consortium." style="border: none; cursor: pointer;">UniProt ID: </acronym></span><span style="font-family: sans-serif; font-size: 16px; background-color: rgb(255, 255, 255);">P05412<br/></span><span class="RECOMMENDED" style="font-size: small; font-family: sans-serif; line-height: 16px; background-color: rgb(255, 255, 255);"><acronym class="RECOMMENDED" title="The name recommended by the UniProt consortium." style="border: none; cursor: pointer; font-style: italic;">Recommended name:</acronym></span></div><span class="RECOMMENDED" style="font-style: normal; font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"><span class="FULL" style="padding-left: 1em;">Transcription factor AP-1</span></span><div class="alternatives" style="font-style: normal; font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"><acronym class="ALTERNATIVE" title="A synonym of the recommended name." style="border: none; cursor: pointer; font-style: italic;">Alternative name(s):</acronym><br/><span style="padding-left: 1em;"><acronym class="names FULL" style="border: none; cursor: pointer; padding-left: 1em;"></acronym></span><span class="FULL_NAME">Activator protein 1</span><br/><acronym class="names SHORT" title="Abbreviation of the full name or an acronym." style="border: none; cursor: pointer; padding-left: 2em; font-size: smaller;">Short name=</acronym><span class="SHORT_NAME" style="font-size: smaller;">AP1</span></div>

2015-11-15T18:45:36Z

<font face="Georgia" size="2"><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Hepatocyte growth factor</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (hepapoietin A; scatter factor) [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P14210" style="text-decoration: none; background-color: rgb(255, 255, 255);">P14210</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3082" ref="ordinalpos=1&ncbi_uid=3082&link_uid=3082" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">HGF</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">3082</span></font></div>

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<font face="Georgia" size="2"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">Nuclear factor of kappa light polypeptide gene enhancer in B-cells inhibitor, alpha [</span><em style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P25963" style="text-decoration: none; background-color: rgb(255, 255, 255);">P25963</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/4792" ref="ordinalpos=1&ncbi_uid=4792&link_uid=4792" style="line-height: 17.999801635742188px; white-space: nowrap; background-color: rgb(255, 255, 255);">NFKBIA</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 16.19982147216797px;">4792</span></font></div>

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<font face="Georgia" size="2">Represents proteasomal IKBa degradation [1]. </font>

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<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Mitogen-activated protein kinase kinase 7 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/O14733" style="text-decoration: none; background-color: rgb(255, 255, 255);">O14733</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/5609" ref="ordinalpos=1&ncbi_uid=5609&link_uid=5609" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">MAP2K7</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;"> </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">5609</span></font></div>

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<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">ELK1, member of ETS oncogene family [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P19419" style="text-decoration: none; background-color: rgb(255, 255, 255);">P19419</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/2002" ref="ordinalpos=1&ncbi_uid=2002&link_uid=2002" style="color: rgb(100, 42, 143); line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">ELK1</a></font></div><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 2002</font></span></div>

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<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Mitogen-activated protein kinase 11 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q15759" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q15759</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/5600" ref="ordinalpos=1&ncbi_uid=5600&link_uid=5600" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">MAPK11</a><span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;"> </span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">5600</span></font></div>

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<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Mitogen-activated protein kinase 8 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P45983" style="text-decoration: none; background-color: rgb(255, 255, 255);">P45983</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/5599" ref="ordinalpos=5&ncbi_uid=5599&link_uid=5599" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">MAPK8</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">5599</span></font></div>

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\r\n \r\n \r\n <div class="page" title="Page 22">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Canonical heterotrimeric NEMO-containing IKB kinase (IKK) complexes [1]. </font></p>\r\n \r\n \r\n \r\n <p style="font-size: 10pt; font-family: Arial, Verdana;"><span style="font-family: ArialMT; font-size: 10pt;"> </span></p>\r\n </div>\r\n </div>\r\n </div>

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<br/>

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\r\n \r\n \r\n <div class="page" title="Page 21">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Activated (canonical) IKK complex; primarily\r\nattributable to catalytic IKKb activity [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

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<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Mitogen-activated protein kinase kinase 3 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P46734" style="text-decoration: none; background-color: rgb(255, 255, 255);">P46734</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/5606" ref="ordinalpos=1&ncbi_uid=5606&link_uid=5606" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">MAP2K3</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">5606</span></font></div>

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<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Dual specificity phosphatase 1 [</span><em style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P28562" style="text-decoration: none; background-color: rgb(255, 255, 255);">P28562</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene Name: </span><span class="highlight" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><a href="http://www.ncbi.nlm.nih.gov/gene/1843" ref="ordinalpos=1&ncbi_uid=1843&link_uid=1843" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">DUSP1</a></span></font></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.77777862548828px;">1843</span></font></div><div style="font-size: 10pt; font-family: Arial, Verdana;"><span style="font-family: arial, helvetica, clean, sans-serif; font-size: 13.333333969116211px; line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><br/></span></div>

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<span style="font-family: Georgia; font-size: small;">Dummy Species [1]. </span>

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<font size="2" face="Georgia">Irak4, myd88, and tollip are all required for the activation of irak1. Irak-m and irak-c are both inhibitors of irak1 and are both dominant over the activators [1]. </font>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"><font face="Georgia">IRAK1c dimerizes with IRAK1 stopping autophosphorylation of IRAK1 and thereby inhibiting it [1,2]. </font></span>

<p style="orphans: 3; widows: 3; line-height: 1.5em; margin: 0.4em 0px 0.5em; font-size: 12px; background-color: rgb(255, 255, 255);"><font face="Georgia"><span style="line-height: 1.5em; font-size: 10pt;">Presence of IRAK4 </span><span style="line-height: 1.5em; font-size: 10pt;">phosphorylation of critical residue(s) within the kinase activation loop of IRAK1 [1,3,4]. </span></font></p>

<span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"><font face="Georgia">MyD88 binds inactive IRAK1 and assists in activating it [1,6]. </font></span>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"><font face="Georgia">Tollip interaction leads to IRAK1 release and activation [1,2,7,8].</font></span>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"><font face="Georgia">IRAK-M inhibits IRAK1 [1,5]. </font></span>

S_49 1 S_74 1 S_51 1 S_60 1 S_82 1

<span style="font-family: Georgia; font-size: small;">Cebpb and Cepbd can each activate dum_cebp_saa [1]. </span>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Cebpd activates the timescale dummy node dum_cebp_saa [1]. </span>

S_11 1 S_55 1

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Il1a and Il1b can each activate dum_il1_r2 [1]. </span>

<span style="font-family: Georgia; font-size: small;">Il1b activates the timescale dummy node dum_il1_r2 [1]. </span>

<span style="font-family: Georgia; font-size: small;">Il1a activates the timescale dummy node dum_il1_r2 [1]. </span>

S_7 1 S_101 1

<font face="Georgia">HNF4a or NFKB can each independently activate iNOS [1]. </font>

<font face="Georgia"><span style="font-size: 10pt;">HNF4a</span><span style="font-size: 10pt;"> </span><span style="font-size: 10pt;">increases iNOS gene expression [1,2]. </span></font>

<font face="Georgia"><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">IL-1B </span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">induces iNOS expression via NF-</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">?</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">B activation [1,3,4].</span></font>

S_39 1 S_93 1

<font face="Georgia" size="2">Tpl2_degr activates tdum_tpl2_degr_tp2 [1]. </font>

<span style="font-family: Georgia; font-size: small;">Timescale dummy activation [1]. </span>

S_75 1

<font face="Georgia">IL8 is activated by the presence AP1, cFOS and NFKB. KSRP and TTP are both inhibitors of IL8 and both are dominant over all activators [1]. </font>

<font face="Georgia"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">KSRP interacts with IL-8 mRNA </span><span style="font-size: 10pt;">adenine/uridine-rich elements</span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">, promoting the deadenylation and degradation of IL-8 transcripts [1,4,5]. </span></font>

<font face="Georgia" size="2"><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">TTP mediates </span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">degradation</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"> of IL-8 mRNA transcripts [1,4,6,7,8]. </span></font>

<font face="Georgia"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">c-Fos synergises with NF-</span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">?</span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">B p65 in transactivating IL-8 gene expression via AP1 [1,2,3]. </span></font>

<span style="font-family: Georgia; font-size: 10pt; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">c-Fos synergises with NF-</span><span style="font-family: Georgia; font-size: 10pt; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">?</span><span style="font-family: Georgia; font-size: 10pt; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">B p65 in transactivating IL-8 gene expression via AP1 [1,2,3]. </span>

S_103 1 S_22 1 S_93 1 S_12 1 S_71 1

<span style="font-family: Georgia; font-size: small;">Soluble IL-1RII activates </span><span style="font-family: Georgia; font-size: small;"> IL-1b</span><span style="font-family: Georgia; font-size: small;"> [1]. </span>

<span style="font-family: Georgia; font-size: small;">Soluble IL-1RII binds IL-1b and activates it [1,2]. </span>

S_108 1

<font face="Georgia" size="2">iNOS and NFKB each deactivate ROS [1]. </font>

<font face="Georgia" size="2">NF-KB activates ferritin heavy chain and superoxide dismutase 2 gene expression (shown in TNFa-treated MEFs) [1,3]. This prevents ROS buildup [1,4]. </font>

<font face="Georgia" size="2">The antioxidant iNOS (activated by the hepatocellular redox state) counteracts ROS by generating nitrous oxide as an free radical to fight infection and protect tissues [1,2]. </font>

S_93 1 S_4 1

<font face="Georgia" size="2">SAP1 can be activated by erk12, jnk or nuc_p38 [1]. </font>

<font face="Georgia" size="2">IL-1 was not found to induce JNK -dependent SAP-1 activity in CHO cells, but SAP-1 is known to be acted on by p38, ERK and JNK [1,2,3]. </font>

<span style="font-family: Georgia; font-size: small;">SAP-1 is known to be acted on by p38, ERK and JNK [1,2]. </span>

<font face="Georgia" size="2">p38 phosphorylates SAP-1 in response to IL-1 leading to transcriptional activation. Shown in IL-1 treated CHO and NIH 3t3 cells [1,2,3]. </font>

S_111 1 S_59 1 S_112 1

\r\n \r\n \r\n <div class="page" title="Page 32">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font size="2" face="Georgia">  Irak4, myd88, and tollip are all required for activation of irak2. Irak1c inhibits irak2 and is dominant over all activators [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<p style="orphans: 3; widows: 3; line-height: 1.5em; margin: 0.4em 0px 0.5em; font-size: 12px; background-color: rgb(255, 255, 255);"><span style="font-size: 10pt;"><font face="Georgia">Kinase-dead IRAK1c dimerizes with IRAK2 and prevents its phosphorylation [1,3]. </font></span></p>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"><font face="Georgia">IRAK4 phosphorylates IRAK2 and activates it [1,6]. </font></span>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"><font face="Georgia">MyD88 links IRAK2 via N-terminal death domains and activates thereby activates it [1,5]. </font></span>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Tollip associates with dimerized IRAK in the cytosol and blocks its activation [1,2,3,4,]. </font></span>

S_49 1 S_74 1 S_51 1 S_60 1

\r\n \r\n \r\n <div class="page" title="Page 47">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Erk12 or nuc_p38 can each independently activate cebpb [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia" size="2"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">ERK1/2 have been found to phosphorylate C/EBP</span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">? [1,2]. </span></font>

<font face="Georgia" size="2">p38 is required for post-translational modifications that activate <span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">C/EBP</span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">? [1,3]. </span></font>

S_59 1 S_111 1

<font face="Georgia" size="2">MK2 is a negative regulator of TTP [1]. </font>

<font face="Georgia" size="2">MK2 causes phosphorylation at S52 and S178 and thereby reduces its affinity to its substrate and lowers its destabilizing effect on mRNAs as shown in anisomycin-treated NIH 3t3 cells and HEK293 cells [1,2,3]. </font>

S_95 1

<font face="Georgia" size="2">Ikkb_a activate p105_degr [1]. </font>

<font face="Georgia" size="2">IKK and IKKb bind p105 at its death domain and phosphorylate it causing proteolysis of p105. This activity has been shown in response to TNFa or LPS, and IL-1 [1,2,3,4]. Phosphorylation of p105 by IKKs at S927 or S932 may target p105 for BTrCP-catalyzed polyubiquitination causing degradation in response to TNFa and IL-1 [1,5,6]. </font>

S_115 1

\r\n\r\n\r\n\r\n\r\n\r\n\r\n<p class="p1"><font face="Georgia" size="2">Erk12, jnk or nuc_p38 can activate ATF2 [1]. </font></p>

<font face="Georgia" size="2"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">JNK </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">binds and </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">phosphorylates ATF2 at T69 and T71 </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">increasing </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">transcriptional activity [1,2,3]. </span></font>

<font face="Georgia" size="2"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">ERK1/2 </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">can phosphorylate ATF2-T71 </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">and activate ATF2</span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"> [1,3]. </span></font>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">p38 </span><span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">binds and </span><span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">phosphorylates ATF2 at T69 and T71 </span><span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">increasing </span><span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">transcriptional activity [1,2,3]. </span>

S_112 1 S_59 1 S_111 1

<span style="font-family: Georgia; font-size: small;">Ikkab_nemo is activated by the presence of ikkb and nemo [1]. </span>

<span style="font-family: Georgia; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">NEMO forms dimers with IKKb [1,2,3,4,5,6,7,8]. </span>

S_99 1 S_19 1

\r\n \r\n \r\n <div class="page" title="Page 49">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><span style="font-family: Georgia;">AP1 and CEBPB are both required to activate lbp [1]. </span></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia">AP1 and CEBPB activate lbp [1,2,3,4]. </font>

<span style="font-family: Georgia;">AP1 and CEBPB activate lbp [1,2,3,4]. </span>

S_11 1 S_103 1

sil1r12 activates sil1r_ap.

sil1r12 increases the binding affinity of sil1r_ap for for IL-1α and -β.

S_108 1

\r\n \r\n \r\n <div class="page" title="Page 42">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia">a20 inactivates NEMO [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia">When ABIN2 binds a20 and activates it, they bind polyubiquitinated NEMO (potentially at both the UBAN and the 4th CC domain as shown in TNF-treated HEK293T cells) [1,2,3]. This inhibits NF-kB activation (shown in IL-1 treated HEK293Tcells) [1,2]. This inhibition is probably because a20  out competes upstream substrates for NEMO interaction (shown in co-expression studies in HEK293T cells) [1,4]. This leads to NEMO degradation by the proteasome [1,5]. </font>

S_65 1

\r\n \r\n \r\n <div class="page" title="Page 39">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font size="2" face="Georgia">MK2 and Nuc_p38 are both required for activation of cyt_p38 [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia" size="2">Nuclear p38 is required to phosphorylate MK2, which causes the transport of p38 into the cytosol [1,2]. </font>

<span style="font-family: Georgia; font-size: small;">Nuclear p38 is required to phosphorylate MK2, which causes the transport of p38 into the cytosol [1,2]. </span>

S_95 1 S_111 1

\r\n \r\n \r\n <div class="page" title="Page 52">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">MSK1 and dum_sap1_or_elk_cfos are both required for activation of cFOS [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia" size="2"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Active SAP-1 and/or Elk-1 interact with SRF (small response factor), forming a ternary complex that binds to the SRE (small response element) in the </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-style: italic;">cfos </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">promoter and produces increased cFOS gene expression [1,2,3,4]. </span></font>

<font face="Georgia" size="2"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">MSK1 catalyzes CREB (cAMP-response element binding protein) S133 phosphorylation which causes </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">and subsequent CREB:CRE (cAMP response element) association with the </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-style: italic;">c-fos </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">promoter causing c-Fos expression [1,5,6].</span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"> </span></font>

S_52 1 S_37 1

<font face="Georgia">IL1r1 is an activator of il1rc, while il1r2 and sil1r12 are both inhibitors of il1rc. Both inhibitors are dominant over il1r1 [1]. </font>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"><font face="Georgia">IL-1 binding to IL-1R leads to interaction of transmembrane IL-1R and IL-1RAcP, and thereby activates il1rc [1,2,3]. </font></span>

<font face="Georgia">IL1r2 inhibits il1rc [1,4,5,6]. </font>

<span style="font-family: Georgia;">Sil1r12 inhibits il1rc [1,4,5,6]. </span>

S_100 1 S_108 1 S_97 1

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Mek4 and mek7 can each activate dum_mek4_or_7_jnk [1]. </span>

<span style="font-family: Georgia; font-size: small;">Mek4 activates the timescale dummy node dum_mek4_or_7_jnk [1]. </span>

<span style="font-family: Georgia; font-size: small;">Mek7 activates the timescale dummy node dum_mek4_or_7_jnk [1]. </span>

S_107 1 S_53 1

\r\n \r\n \r\n <div class="page" title="Page 44">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">TAK1 activates NIK [1].</font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia">TAK1 activates NIK by phosphorylating it (shown in HEK293 cells) [1,2]. </font>

S_57 1

<font face="Georgia" size="2">MSK1 activates cJun_gene [1]. </font>

\r\n \r\n \r\n \r\n <div class="page" title="Page 51">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Histone H3-S10 phosphorylation by MSK1 activates cJun_gene [1,2].</font></p>\r\n </div>\r\n </div>\r\n </div>

S_37 1

\r\n \r\n \r\n <div class="page" title="Page 44">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia">NIK and IKKaa are required to activate nc_nfkb_pathway [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font size="2" face="Georgia"><font size="2">IKKa homodimers act independently of NEMO upstream of the NF-KB </font>non-canonical<font size="2"> pathway [1,2,3]. </font></font>

<font face="Georgia"><font size="2">NIK phosphorylates IKKa kinase at S176 in the kinase activation loop in response to IL-1's signal (shown in HEK293 cells) [3]; this is thought to be required for p100 processing in the </font><font size="2">non-canonical</font><font size="2"> NF-KB pathway [4]. Ryll et all 2011 proposed relevance to hepatic IL-1 signaling [1]. </font></font>

S_25 1 S_33 1

<font face="Georgia" size="2">PI3K activates PIP3, while PTEN deactivates PIP3 and is dominant over PI3K [1]. </font>

<font face="Georgia" size="2">PTEN dephosphorylates PIP3 to PIP2 [1,3].</font>

<font face="Georgia" size="2">PI3K activates the phosphorylation of PIP2 and generates PIP3. PI3K directly correlates to PIP3 concentration in IL-1 treated HepG2 cells [1,2,3]. </font>

S_79 1 S_46 1

<font face="Georgia" size="2">p50 is activated by p105_degr [1]. </font>

<font face="Georgia" size="2">p50 is generated by post-translational proteolysis of the glycine-rich region within C-terminal of the p50 half of p105 which must be cleaved to allow p105 to enter the 26S region of the proteasome [1,2,3]. </font>

S_13 1

<font face="Georgia" size="2">Irak1 activates Traf6 [1]. </font>

<font face="Georgia" size="2">IRAK1 binds with TRAF6 preventing its complex with TAK1 in the NF-KB pathway as shown in HEK293 cells [1,2,3]. </font>

S_1 1

<font face="Georgia">TPL2 activates MEK1 [1]. </font>

<font face="Georgia">TPL2 activates MEK1 by phosphorylating it [1,2,3,4]. </font>

S_50 1

<font face="Georgia">IKKa activates IKKaa [1]. </font>

\r\n \r\n \r\n <div class="page" title="Page 42">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia">IKKa forms dimers activating IKKaa [1,2,3]. </font></p>\r\n </div>\r\n </div>\r\n </div>

S_21 1

<font face="Georgia" size="2">dum_ikkab_nemo_akt_or_ck2_p65 activates p65, while SOCS1 inactivates p65 and is dominant over dum_ikkab_nemo_akt_or_ck2_p65 [1]. </font>

<font face="Georgia" size="2">SOCS1 inhibits the activation of p65. Shown in MEFs to inhibit p65 via increasing rate of ubiquitination [1,9]. </font>

<font face="Georgia" size="2">IKKB is involved in the phosphorylation of S536 in the C-terminal activation domain of p65, shown in HeLa and HepG2 [1,2,3,4,5]. IKKB is also shown to phosphorylate p65 at S568 while complexed with IKB shown in IL-1 treated Hep3B and primary human hepatic stellate cells [1,6]. IL-1 induces phosphorylation of serines by CK2, shown in HepG2 cells [1,7]. Serine-276 must be phosphorylated for p65 to simulate IL-6 production [1,8]. </font>

S_102 1 S_36 1

<font face="Georgia" size="2">il1r2 activates tdum_il1r2_il1rc [1]. </font>

<span style="font-family: Georgia; font-size: small;">Timescale dummy activation [1]. </span>

S_97 1

\r\n \r\n \r\n <div class="page" title="Page 50">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia">MSK1 can be activated by nuc_p38 or ERK12 [1]. </font></p>\r\n </div>\r\n </div>\r\n \r\n </div>

<font face="Georgia">ERK1/2 can phosphorylate MSK1 and activate it [1,2,3]. </font>

<span style="color: rgb(79, 79, 79); font-family: Georgia; font-size: 11.818181991577148px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">p38 can phosphorylate MSK1 and activate it [1,2,3]. </span>

S_59 1 S_111 1

<font face="Georgia" size="2">Ikkab_nemo or ikkabb_nemo can each independently activate <span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">dum_ikkab_or_ikkbb_nemp_ikkb_a [1]. </span></font>

<span style="font-family: Georgia; font-size: small;">Ikkab_nemo activates the timescale dummy node dum_ikkab_or_ikkbb_nemp_ikkb_a [1]. </span>

<span style="font-family: Georgia; font-size: small;">Ikkbb_nemo activates the timescale dummy node dum_ikkab_or_ikkbb_nemp_ikkb_a [1]. </span>

S_90 1 S_16 1

<font face="Georgia">Nuc_p38 and ROS are both required for activation of hnf4a [1]. </font>

<font face="Georgia">ROS induces binding of hnf4a to its activator [1]. </font>

<font face="Georgia" size="2">Nuclear p38 is critical for up-regulation of hnf4a [1,2,3]. </font>

S_111 1 S_8 1

<font face="Georgia">MK2 activates hsp27_ps [1]. </font>

\r\n \r\n \r\n <div class="page" title="Page 38">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">HSP27 is phosphorylated at\r\nS78 and S82 by activated MK2 [1,2]. </font></p>\r\n </div>\r\n </div>\r\n </div>

S_95 1

\r\n \r\n \r\n <div class="page" title="Page 46">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><span style="font-family: Georgia; font-size: small;">Ikkaa_nemo and Mekk3 cooperatively activate ikka_a [1]. </span></p>\r\n </div>\r\n </div>\r\n </div>

<font size="2" face="Georgia">Ikkaa_nemo and Mekk3 activate ikka_a [1,2]. </font>

<span style="font-family: Georgia; font-size: small;">Ikkaa_nemo and Mekk3 activate ikka_a [1,2]. </span>

S_77 1 S_113 1

<font face="Georgia" size="2">CEBPB or CEBPd can each activate pro_hgf [1]. </font>

<span style="font-family: Georgia; font-size: small;">IL-1 causes HGF gene expression and secretion (shown in MRC-5 cells) [1,2].  C/EBPB activates the HGF promoter. Shown in NIH 3t3 fibroblasts [1,3]. </span>

<font face="Georgia" size="2">IL-1 causes HGF gene expression and secretion (shown in MRC-5 cells) [1,2].  C/EBPB activates the HGF promoter. Shown in NIH 3t3 fibroblasts [1,3]. </font>

S_11 1 S_55 1

<font face="Georgia" size="2">hsp27_ps activates tdum_hsp27_ps_traf6_ub [1]. </font>

<span style="font-family: Georgia; font-size: small;">Timescale dummy activation [1]. </span>

S_40 1

<font face="Georgia" size="2">irak1c activates tdum_irak1c_irak12 [1]. </font>

<span style="font-family: Georgia; font-size: small;">Timescale dummy activation [1]. </span>

S_60 1

<font face="Georgia">NFKB, AP1, CEBPB, and GSK3 are all required to activate IL-6. KSRP and TTP are both inhibitors of IL-6 and are dominant over the positive regulators [1]. </font>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"><font face="Georgia">KSRP causes the deadenylation and degradation of IL-6 transcripts [1,6]. </font></span>

<font face="Georgia"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">TTP binds adenine/uridine-rich elements within the 3?-untranslated region of cytokine mRNA, targeting mRNA transcripts for degradation possibly by deadenylation to maintain low levels of inflammatory cytokines [1,7,8,9]. </span></font>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">AP-1 contributes IL-6 gene expression [1,2,3].</font></span>

<font face="Georgia"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">C/EBPB </span><span style="font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">contributes IL-6 gene expression [1,2,3].</span></font>

<font face="Georgia"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">GSK3B</span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"> </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">controls promoter- specific NF-</span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">?</span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">B recruitment and is essential for efficient IL-6 and CCL2 expression [1,5]. </span></font>

<span style="color: rgb(79, 79, 79); font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">NFKB contributes IL-6 gene expression [1,2,3].</span>

S_103 1 S_11 1 S_86 1 S_93 1 S_71 1 S_12 1

<font face="Georgia" size="2">SAA is activated by dum_cebp_saa and NFKB [1]. </font>

<font face="Georgia" size="2">CEBPB (or CEBPD) and NFKB cause SAA2 expression. Shown in HepG2 and murine embryonic liver cells. Phosphorylation of CEBPBD increases transactivation potential [1,2,3]. </font>

<span style="font-family: Georgia; font-size: small;">CEBPB (or CEBPD) and NFKB cause SAA2 expression. Shown in HepG2 and murine embryonic liver cells [1,2]. </span>

S_2 1 S_93 1

\r\n \r\n \r\n <div class="page" title="Page 31">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia">Irak4 is activated by myd88 and inactivated by smyd88. The inhibition of smyd88 is dominant over the activaiton by myd88 [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"><font face="Georgia">sMyD88 interaction with irak4 prevents irak1 activation [1,2]. </font></span><span style="font-family: ArialMT; color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"> </span>

<font face="Georgia"><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">IRAK4 becomes phosphorylated on serines and threonines and catalytically active due to autophosphorylation</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"> as a result of MyD88 interaction [1,3,4]. </span></font>

S_74 1 S_98 1

<font face="Georgia" size="2">TPL2 is activated by abin2 and src. p105 and tpl2_degr are negative regulators of tpl2 and are dominant over the positive regulators [1]. </font>

<font face="Georgia" size="2">p105 inhibits the MEK kinase activity of TPL2 [1,2,3,4]. </font>

<font face="Georgia" size="2">TPL2 degradation is a negative regulator of TPL2 [1]. </font>

<font face="Georgia" size="2">Abin2 form a ternary complex with TPL2 and p105 and contributes to TPL2 stability. TLP2 is activated after it is freed from abin2 as shown in LPS treated bone marrow derived macrophages [1,7,8]. </font>

<font face="Georgia" size="2">Src kinase phosphorylates at T290 in the activation loop leads to autophosphorylation of S62 and activation of TPL2 as shown in IL-1 treated HEK293 and HeLa cells [1,5,6]. </font>

S_84 1 S_91 1 S_75 1 S_62 1

<font face="Georgia" size="2">il1rc activates tollip [1]. </font>

<font face="Georgia" size="2">The IL1rc complex recruits tollip as shown in EL-4.6.10 murine lymphoma cells [1,2]. </font>

S_23 1

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Elk1 and sap1 can each activate dum_sap1_or_elk_cfos [1]. </span>

<span style="line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">Elk1 activates the timescale dummy node </span><span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">dum_sap1_or_elk_cfos</span><span style="line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);"> </span><span style="line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">[1]. </span>

<span style="font-size: small; line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; background-color: rgb(255, 255, 255);">Sap1 activates the timescale dummy node </span><span style="font-size: small; font-family: Georgia; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">dum_sap1_or_elk_cfos</span><span style="font-size: small; line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; background-color: rgb(255, 255, 255);"> </span><span style="font-size: small; line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; background-color: rgb(255, 255, 255);">[1]. </span>

S_9 1 S_109 1

<font face="Georgia">Mek4 can be activated by MEKK3 or Tak1_tab [1]. </font>

<font face="Georgia">Tak1 induces MEK4 activation by phosphorylation [1,2]. </font>

<font face="Georgia">Mekk3 directly activates Mek4 by phosphorylation [1,3,4]. </font>

S_77 1 S_57 1

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Irak1 and Irak2 can each activate dum_irak1_or_2_traf6_ub [1]. </span>

<span style="font-family: Georgia; font-size: small;">Irak2 activates the timescale dummy node dum_irak1_or_2_traf6_ub [1]. </span>

<span style="font-family: Georgia; font-size: small;">Irak1 activates the timescale dummy node dum_irak1_or_2_traf6_ub [1]. </span>

S_10 1 S_1 1

\r\n \r\n \r\n <div class="page" title="Page 47">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Expression of CEBPd requires the presence of CK2, JNK and NFKB [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<span style="font-family: Georgia; font-size: small;">The cebpd gene is activated in a JNK dependent manner [1,2]. </span>

<font face="Georgia" size="2">The cebpd gene is activated in a CK2 dependent manner [1,2]. </font>

<span style="font-family: Georgia; font-size: small;">The cebpd gene is activated in a NFKB dependent manner [1,2]. </span>

S_93 1 S_112 1 S_15 1

<font face="Georgia">Mek6 can be activated by mekk3 or Tak1_tab [1]. </font>

\r\n \r\n \r\n \r\n <div class="page" title="Page 37">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><span style="font-size: 10pt;"><font face="Georgia">TAK1\r\nphosphorylates MEK6 at S207 and T211 and activates it [1,3,4]. </font></span></p>\r\n </div>\r\n </div>\r\n </div>

<span style="color: rgb(79, 79, 79); font-family: Georgia; font-size: 11.818181991577148px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Mekk3 directly activates Mek6 by phosphorylation [1,2]. </span>

S_57 1 S_77 1

<font face="Georgia" size="2">Tak1_tab is activated by the presence of traf6_ub, mekk3, and trika1. Tak1_tab is inactivated by cyt_p38. The activity from cyt_p38 is dominate over that of the activators [1]. </font>

<font size="2"><span style="background-color: rgb(255, 255, 255);"><font face="Arial, Verdana" size="2" style="font-family: Georgia;"><span style="line-height: 18px;">IRAK1/TRAF6 interacts with the complex of TAK1/TAB1/TAB2 or 3 and contributes to the phosphorylation of TAB2/3 as shown in IL-1 treated HEK293 cells [1,2,3,4,5,6]. It also leads to the phosphorylation of TAK1 in an IRAK1 dependent manner as shown in TNFa treated HEK293 cells [1,7,8,10]. This enables the association of TRAF6 and TAB2 as shown in IL-1 treated HEK293 cells [1,8]. TAB2 and TAB3 may bind to the K63 linked poly-ubiquinated chains on TRAF6 as shown in IL-1 treated HeLa cells [1,5]. This leads to the ubiquitination of TAB2 and TAB3 by TRAF6 as shown in IL-1 treated HEK293 cells [1,10]. The TRAF6/TAK1/TAB1/TAB2 or 3 complex </span></font><span style="font-family: Georgia; line-height: 18px;">separated</span><font face="Arial, Verdana" size="2"><font face="Georgia"><span style="line-height: 18px;"> from IRAK1 and moves to the cytosol causing TAK1 to become active as </span></font><span style="line-height: 18px;">showing</span><font face="Georgia"><span style="line-height: 18px;"> HEK293 cells [1,11]. </span></font></font></span></font>

<font face="Georgia" size="2">TRAF6/TRIKA1 mediate the ubiquitination of TAK1 at K209. This is required for TRAF6 to interact with TAK1 and MEKK3 as shown in IL-1 treated MEFs [1,15]. </font>

<p style="orphans: 3; widows: 3; line-height: 1.5em; margin: 0.4em 0px 0.5em; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">p38 phosphorylates TAB1 at S423, T431 and S438 as shown in IL-1 treated human epithelial KB cells [1,16]. p38 is thought to further TAB2 at S582 and TAB3 at S60/T404 as shown in IL-1 treated MEFs [1,4,16]. </font></p>

<div style="orphans: 3; widows: 3;"><span style="background-color: rgb(255, 255, 255);"><font size="2" face="Georgia"><span style="line-height: 18px;">MEKK3 is an activator of TAK1 and phosphorylates TAK1's activation loop after TAK1 is polyubiquitinated at K209 as shown in IL-1 treated MEFs and HEK293T cells [1,15]. This interaction occurs through two separate complexes, IRAK1/TRAF6/TAK1 and IRAK1/TRF6/MEKK3 [1,12]. </span></font></span></div>

S_58 1 S_80 1 S_77 1 S_20 1

<font face="Georgia" size="2">Traf6_ub is activated by the joint activity of trika1 and dum_irak1_or_2_traf6_ub. A20, hsp27_ps, and socs3 are all negative regulators and are each dominant over the positive regulators [1]. </font>

<font face="Georgia" size="2">IRAK1 interacts with TRAF6 as shown in co-expression studies in HEK293T cells [1,2,3]. IRAK4 also interacts with IRAK1 and TRAF6  as shown in HEK293 [1,4,5]. Hyper-phosphorylation of IRAK1 may cause dissociation of IRAK1 from TRAF6 to allow ubiquitination of TRAF6 [1,6,7,8]. TRAF6 also catalyzes self ubiquitination [1,12,13].</font>

<font face="Georgia" size="2">SOCS3 inhibits TRAF6 uniquitination, preventing complexing of TRAF6 with TAK1 as shown in IL-1 treated insulinoma-1 cells [1,19]. </font>

<font face="Georgia" size="2">TRIKA1 helps control the addition of non-degrading K63-linked polyubiquitin chains on TRAF6 as shown in HeLa cells [1,10,11,12]. </font>

<font face="Georgia" size="2">A20 inhibits NF-KB activation by interacting with TRAF6 [1,16,17]. A2- removes the K63-linked polyubiquitin using its N-terminal ovarian tumor domain follwoed by a K48-linked substrate polyubiquitination through its ubiquitin ligase domain within the ZnF region stimulating its proteasomal degradation as shown in TNFR1/RIP signaling [1,18]. </font>

<font face="Georgia" size="2">Hsp27 binds TRAF6 and increases its polyubiquitination as shown in HEK293 and HeLa cells [1,14,15].  HSP27 phosphorylation at S78 and S82 by MK2 which promotes TRAF6/HSP27 dissociation as shown in IL-1 treated HeLa cells [1,16]. </font>

S_54 1 S_80 1 S_65 1 S_40 1 S_47 1

\r\n \r\n \r\n <div class="page" title="Page 40">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Erk12 is activated by mek1, and deactivated by mkp1 [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia" size="2">Mek1 activates erk1/2 by phosphorylating T202/Y204 [1,2,3]. </font>

<font face="Georgia" size="2"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">MKP1 selectively interacts with and inactivates ERK2</span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">by dephosphorylation [1,4,5].</span></font>

S_32 1 S_117 1

\r\n \r\n \r\n <div class="page" title="Page 31">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia">MyD88 and tollip are both required for activation of irak1c [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia">MyD88 and tollip activate irak1c [1,2]. </font>

<span style="font-family: Georgia;">MyD88 and tollip activate irak1c [1,2]. </span>

S_74 1 S_51 1

<font face="Georgia">Irs1_ps can be activated by erk12, ikkb_a or jnk [1]. </font>

<div><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"><font face="Georgia">JNK promotes IRS1's phosphorylation at S307 and S312 [1,9,10,11]. </font></span></div>

<p style="orphans: 3; widows: 3; line-height: 1.5em; margin: 0.4em 0px 0.5em; font-size: 11.818181991577148px; background-color: rgb(255, 255, 255);"><span style="font-size: 10pt;"><font face="Georgia">ERK1/2 phosphorylates IRS1 producing irs1_ps [1,2,3,4,5]. </font></span></p>

<font face="Georgia"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">IKKb</span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"> </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">negatively regulates IRS1 by direct serine phosphorylation [1,6,7,8].</span></font>

S_59 1 S_115 1 S_112 1

\r\n \r\n \r\n <div class="page" title="Page 44">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">p105 is negatively regulated by p105_degr [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia" size="2">IL-1 activates p105 degradation by the proteasome. Shown in HeLa cells and human primary synoviocytes [1,2]. </font>

S_13 1

<font face="Georgia" size="2">il1ra activates tdum_il1ra_il12 [1]. </font>

<span style="font-family: Georgia; font-size: small;">Timescale dummy activation [1]. </span>

S_87 1

<span style="font-family: Georgia; font-size: small;">Cebpb and Cepbd can each activate dum_cebp_pro_il1b [1]. </span>

<span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">Cebpd activates the timescale dummy node dum_cebp_</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">pro_il1b </span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">[1]. </span>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Cebpb activates the timescale dummy node dum_cebp_</span><span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">pro_il1b </span><span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">[1]. </span>

S_55 1 S_11 1

<font face="Georgia" size="2">Abin2 activates A20 [1]. </font>

\r\n\r\n\r\n\r\n\r\n<p class="p1"><font face="Georgia" size="2">ABIN2 binds with the C-terminal ZnF domain of A20 at its AHD1 domain and activates A20 (shown in TNF-treated HEK293T cells) [1,2,3].</font></p>

S_84 1

\r\n \r\n \r\n <div class="page" title="Page 49">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Cox2 can be activated by AP1, cJun, dum_cebp_cox2 or NFKB [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">COX2 gene expression can be activated by transcription factor sets including cJun [1,2,3,4].</span>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">COX2 gene expression can be activated by transcription factor sets including AP1 [1,2,3,4].</font></span>

S_96 1 S_93 1 S_81 1 S_103 1

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Mek3, mek4 and mek6 can each activate dum_mek3_or_4_or_6_nuc_p38 [1]. </span>

<span style="font-size: small; font-family: Georgia;">Mek4 activates the timescale dummy node dum_</span><span style="font-size: small; font-family: Georgia; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">mek3_or_4_or_6_nuc_p38</span><span style="font-size: small; font-family: Georgia;"> [1]. </span>

<span style="font-family: Georgia; font-size: small;">Mek3 activates the timescale dummy node dum_</span><span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">mek3_or_4_or_6_nuc_p38</span><span style="font-family: Georgia; font-size: small;"> [1]. </span>

<span style="font-size: small; font-family: Georgia;">Mek6 activates the timescale dummy node dum_</span><span style="font-size: small; font-family: Georgia; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">mek3_or_4_or_6_nuc_p38</span><span style="font-size: small; font-family: Georgia;"> [1]. </span>

S_53 1 S_116 1 S_56 1

<font face="Georgia" size="2">a20 activates tdum_a20_traf6_ub [1]. </font>

<font face="Georgia" size="2">Timescale dummy activation [1]. </font>

S_65 1

<font face="Georgia" size="2">Ap1, cJUN, GSK3 and NFKB are all required for ccl2 activation [1].  </font>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">c-Jun or c-Jun heterodimers (AP1 proteins) recruit RNA polymerase II to the ccl2 locus and increase ccl2 expression [1,2]. </span>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">c-Jun or c-Jun heterodimers (AP1 proteins) recruit RNA polymerase II to the ccl2 locus and increase ccl2 expression [1,2]. </font></span>

<span style="font-family: Georgia; font-size: small;">GSK3 controls NF-KB recruitment to the gene site and is required for CCL-2 expression [1,3]. </span>

<font face="Georgia" size="2">NF-KB recruitment to the gene site is required for CCL-2 expression [1,3]. </font>

S_103 1 S_96 1 S_86 1 S_93 1

\r\n \r\n \r\n <div class="page" title="Page 48">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia">ERK1/2 is an inhibitor of nalp_infl [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia" size="2">Negative regulation of nalp_infl as proposed by Ryll et. al (2011) [1]. Mechanism was proposed based off of findings that ERK1/2 mediates C/EBPb phosphorylation of T266 which increases  C/EBPb association with pro-Casp and stops caspase activation (shown in CCL<sub>4 </sub>treated primary human hepatic stellate cells) [2]. This negative regulation of caspase is thought to prevent build up of IL-1, which is pro-inflammatory and whose signal indirectly activates the inflammasome [1,3]. </font>

S_59 1

<font face="Georgia">Ksrp is deactivated by cyt_p38 [1]. </font>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"><font face="Georgia">p38-catalysed KSRP phosphorylation decreases its activity [1,2]. </font></span>

S_20 1

<span style="font-family: Georgia; font-size: small;">Cebpb and Cepbd can each activate dum_cebp_il1ra [1]. </span>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Cebpb activates the timescale dummy node dum_cebp_il1ra [1]. </font></span>

S_11 1 S_55 1

<font face="Georgia">IKKa activates ikba_diss [1]. </font>

\r\n \r\n \r\n <div class="page" title="Page 46">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">IKKa activation increases IKBa dissolution [1,2,3]. </font></p>\r\n </div>\r\n </div>\r\n </div>

S_41 1

<font face="Georgia">Il1rc activates myd88 [1]. </font>

<font face="Georgia">IL1rc activates myd88 [1,2,3,4]. </font>

S_23 1

<font face="Georgia" size="2">Tpl2 activates tpl2_degr [1]. </font>

<font face="Georgia" size="2">A pool of active TPL2 causes proteolysis of TPL2 as shown in IL-1 treated HeLa and LPS-treated RAW264.7 cells [1,2,3]. </font>

S_50 1

<font face="Georgia" size="2">cJUN, CK2, dum_cebp_pro_il1b, and NFKB are all required to activate pro_il1b [1]. </font>

<font face="Georgia" size="2">CK2 recruits NF-KB and the interferon regulatory factor to the il1B promoter by activating phosphorylation of S148 on PU.1. This stimulates IRF-4 recruitments and facilitates pol II [1,4]. </font><span style="font-family: Georgia; font-size: small;">Binding of IRF4, IRF8, NF-KB p65, c-Jun homodimers, C/EBpB and PU.1 may all be involved in the regulation of il1B regulation [1,4]. </span>

<font face="Georgia" size="2">PU.1 and CEBPB recruit c-JUN dimers and together activate Pol II at the il1B promoter as shown for RAW cells (murine macrophages) [1,2,3]. Binding of IRF4, IRF8, NF-KB p65, c-Jun homodimers, C/EBpB and PU.1 may all be involved in the regulation of il1B regulation [1,4]. </font>

<span style="font-family: Georgia; font-size: small;">PU.1 and CEBPB recruit c-JUN dimers and together activate Pol II at the il1B promoter as shown for RAW cells (murine macrophages) [1,2,3]. </span><span style="font-family: Georgia; font-size: small;">Binding of IRF4, IRF8, NF-KB p65, c-Jun homodimers, C/EBpB and PU.1 may all be involved in the regulation of il1B regulation [1,4]. </span>

<span style="font-family: Georgia; font-size: small;">CK2 recruits NF-KB and the interferon regulatory factor to the il1B promoter by activating phosphorylation of S148 on PU.1. This stimulates IRF-4 recruitments and facilitates pol II [1,4]. </span><span style="font-family: Georgia; font-size: small;">Binding of IRF4, IRF8, NF-KB p65, c-Jun homodimers, C/EBpB and PU.1 may all be involved in the regulation of il1B regulation [1,4]. </span>

S_64 1 S_15 1 S_96 1 S_93 1

<font face="Georgia">Traf6 and traf6_ub  can each independently activate mekk3 [1]. </font>

\r\n \r\n \r\n <div class="page" title="Page 37">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><span style="font-size: 10pt;"><font face="Georgia">TRAF6 recruits MEKK3 and activates it [1,2,3]. </font></span></p>\r\n </div>\r\n </div>\r\n </div>

\r\n \r\n \r\n <div class="page" title="Page 37">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><span style="font-size: 10pt;"><font face="Georgia">TRAF6 associates with MEKK3 and activates it [1,2,3,4,5].</font></span><span style="font-family: ArialMT; font-size: 10pt;"> </span></p>\r\n </div>\r\n </div>\r\n </div>

S_31 1 S_58 1

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Dum_tak1_tab_or_mekk3_ikkb_a can be activated by the joint activity of tak1_tab and irak1_ub, or by mekk3</span><span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"> [1]. </span>

<span style="line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">Irak1_ub activates the timescale dummy node dum_tak1_tab_or_mekk3_ikkb_a</span><span style="line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);"> </span><span style="line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">[1]. </span>

<span style="font-size: small; line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; background-color: rgb(255, 255, 255);">Tak1_tab activates the timescale dummy node dum_tak1_tab_or_mekk3_ikkb_a</span><span style="font-size: small; line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; background-color: rgb(255, 255, 255);"> </span><span style="font-size: small; line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; background-color: rgb(255, 255, 255);">[1]. </span>

<span style="font-size: small; line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; background-color: rgb(255, 255, 255);">Mekk3 activates the timescale dummy node dum_tak1_tab_or_mekk3_ikkb_a</span><span style="font-size: small; line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; background-color: rgb(255, 255, 255);"> </span><span style="font-size: small; line-height: 18px; orphans: 3; widows: 3; font-family: Georgia; background-color: rgb(255, 255, 255);">[1]. </span>

S_57 1 S_94 1 S_77 1

<font face="Georgia" size="2">Il1rc or myd88 activates PI3K [1]. </font>

<font size="2" face="Georgia"><font size="2">IL-1 activates PI3K as shown in HepG2 cells [1,2,3]. IL-1 </font>simulates<font size="2"> formation of IL-1RI (phosphorylated Y496)/p85 complex [1,4] and IL-1RAcP/p85 interaction [1,5]. </font></font>

<font face="Georgia" size="2">MyD88 is shown to interact with the IL-1 complex in EL4.NOB-1 cells during activation of PI3K [1,4]. </font>

S_74 1 S_23 1

<font face="Georgia" size="2">Cebpb and Cepbd can each activate dum_cebp_cox2 [1]. </font>

<span style="font-family: Georgia; font-size: small;">Cebpd activates the timescale dummy node dum_cebp_cox2 [1]. </span>

<font face="Georgia" size="2">Cebpb activates the timescale dummy node dum_cebp_cox2 [1]. </font>

S_11 1 S_55 1

<font face="Georgia" size="2">IRAK1 or IRAK4 can each activate pellino [1]. </font>

<span style="font-family: Georgia; font-size: small;">IRAK4 catalyzes the phosphorylation of Pellino isoforms and enhances their E3 ligase function. Shown in HEK293 [1,2,3]. </span>

<font face="Georgia" size="2">IRAK1 catalyzes the phosphorylation of Pellino isoforms and enhances their E3 ligase function. Shown in HEK293 [1,2,3]. </font>

S_1 1 S_49 1

<font face="Georgia" size="2">Ap1 and ATF2 are both required to activate uPA [1]. </font>

<font face="Georgia" size="2">uPA gene expression is activated by c-JUN:ATF2 hetero and/or ATF2 homodimers as shown in HepG2 cells [1,2]. </font>

<span style="font-family: Georgia; font-size: small;">uPA gene expression is activated by c-JUN:ATF2 hetero and/or ATF2 homodimers as shown in HepG2 cells [1,2]. </span>

S_103 1 S_14 1

<font face="Georgia" size="2">Gsk3 is inactivated by akt [1]. </font>

\r\n \r\n \r\n <div class="page" title="Page 41">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Akt phosphorylates gsk3 and thereby deactivates it [1,2,3].</font></p>\r\n </div>\r\n </div>\r\n </div>

S_114 1

<font face="Georgia"><font size="2">Il1ra can be activated by the joint activity of nfkb and dum_cebp_il1ra or by sil1r12 [1]. </font></font>

<font face="Georgia" size="2">Il1ra is activated by timescale dummy cebp il1ra [1]. </font>

<span style="font-family: Georgia; font-size: small;">Soluble IL-1RII binds IL-1ra and activates it [1,2]. </span>

\r\n\r\n\r\n\r\n\r\n\r\n\r\n<p class="p1"><font face="Georgia" size="2"> NF-kB p65 and C/EBP delta  activate IL-1Ra gene expression [1,3]. </font></p>

S_72 1 S_93 1 S_108 1

<font face="Georgia" size="2">cyt_p38 is activated by tdum_cyt_p38_tak1_tab [1]. </font>

<span style="font-family: Georgia; font-size: small;">Timescale dummy activation [1]. </span>

S_20 1

<font face="Georgia" size="2">MKP1 activates tdum_mkp1_p38_jnk_erk12 [1]. </font>

<span style="font-family: Georgia; font-size: small;">Timescale dummy activation [1]. </span>

S_117 1

<font face="Georgia" size="2">Ikkab_nemo is activated by the presence of ikka, ikkb and nemo [1]. </font>

<span style="font-family: Georgia; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">NEMO forms dimers with IKKa and IKKb [1,2,3,4,5,6,7,8]. </span>

S_21 1 S_99 1 S_19 1

\r\n \r\n \r\n <div class="page" title="Page 48">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Il1b_new is activated by nalp_infl and pro_il1b [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<span style="color: rgb(79, 79, 79); font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">pro-IL-1B</span><span style="color: rgb(79, 79, 79); font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"> </span><span style="color: rgb(79, 79, 79); font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">is cleaved at D116 by Casp1 in a NALP-inflammasome associated manner, yielding active IL-1B [1,2,3,4]. </span>

<font face="Georgia" size="2"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">pro-IL-1B</span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"> </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">is cleaved at D116 by Casp1 yielding active IL-1B [1,2,3,4]. </span></font>

S_76 1 S_70 1

\r\n \r\n \r\n <div class="page" title="Page 47">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia">p50 and p65 are both required to activate NF-KB. IkBa is an inhibitor of NF-KB and is dominant over the activators [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia">p50 must be present for it to form a p50:p65 heterodimer. Il-1 has been shown to induce nuclear translocation of p50 and p65 in HepG2 cells [1,3,4]. </font>

<span style="font-family: Georgia;">p65 must be present for it to form a p50:p65 heterodimer. Il-1 has been shown to induce nuclear translocation of p50 and p65 in HepG2 cells [1,3,4]. </span>

<font face="Georgia">IkBa interacts with the NF-KB p50:p65 heterodimer and blocks its transcriptional activity. When IkBa is degraded, this inhibition is removed [1,2]. </font>

S_30 1 S_34 1 S_105 1

<font face="Georgia">Trika1 and pellino are both required for irak1_ub [1]. </font>

<span style="font-family: Georgia;">Pellino isoforms participate in TRIKA1-supported formation of K63-pUb IRAK1 [1,2,3]. </span>

S_83 1 S_80 1

<font face="Georgia">Mk2 is activated by nuc_p38 [1]. </font>

<font face="Georgia">p38 interacts with and activates mk2 [1,2,3,4]. </font>

S_111 1

<font face="Georgia" size="2">cJun_gene and JNK can each activate cJun [1]. </font>

\r\n \r\n \r\n \r\n <div class="page" title="Page 51">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">JNK phosphorylates\r\nc-Jun at S63 and/or S73 within its\r\nN-terminal transactivation domain (TAD) and increasing its transcriptional activity [1,2]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia" size="2">When the cJUn_gene is active, cJUn is produced [1,3,4,5]. </font>

S_112 1 S_27 1

\r\n \r\n \r\n <div class="page" title="Page 30">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><span style="font-family: Georgia; font-size: small;">Dum_il_r1 is an activator of il1r, while il1ra is an inhibitor of il1r1 and is dominant over the activator [1]. </span></p>\r\n </div>\r\n </div>\r\n </div>

<span style="font-family: Georgia; font-size: small;">IL-1Ra competes for receptors and stops heterodimerization. IL-1Ra is an inhibitor of il1r2 formation [1,3,4,5]. </span>

<span style="font-family: Georgia; font-size: small;">Il1r2 is activated by both IL-1a and IL-1b [2,3]. These two proteins activate the timescale dummy node dum_il_r2, which in turn activates il1r2 [1]. </span>

S_3 1 S_87 1

<font face="Georgia" size="2">Dum_il_r1 is an activator of il1r, while il1ra is an inhibitor of il1r1 and is dominant over the activator [1]. </font>

<font face="Georgia" size="2">Il1r1 is activated by both IL-1a and IL-1b [2,3,4]. These two proteins activate the timescale dummy node dum_il_r1, </font><span style="font-family: Georgia; font-size: small;">which in turn activates il1r2 [1].</span><font face="Georgia" size="2"> </font>

<font face="Georgia" size="2">IL-1Ra stops recruitment of receptors and stops heterodimerization. IL-1Ra is an inhibitor of il1r1 formation [1,5]. </font>

S_118 1 S_87 1

<font face="Georgia" size="2">sil1r12 activates il1ra [1]. </font>

\r\n\r\n\r\n\r\n\r\n\r\n<p class="p1"><font face="Georgia" size="2">Soluble IL-1RII binds IL-1a and activates it [1,2]. </font></p>

S_108 1

\r\n \r\n \r\n \r\n <div class="page" title="Page 45">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><span style="font-size: 10.000000pt; font-family: 'ArialMT'">IL-1 mediates the regulatory S536-\r\nphosphorylation within the C-terminal\r\ntransactivation domain 1 (TAD1) of p65\r\nIKK</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">?</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">-dependently (and via additional\r\nkinases, which may act redundantly),\r\nincreasing its transcriptional activity (as\r\nshown in in HeLa</span><span style="font-size: 6.000000pt; font-family: 'ArialMT'; vertical-align: 5.000000pt">31a </span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">and HepG2 cells</span><span style="font-size: 6.000000pt; font-family: 'ArialMT'; vertical-align: 5.000000pt">4a</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">) </span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">?\r\n</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">evidences for a PI3K-initiated NF-</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">?</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">B\r\nactivation pathway distinct from I</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">?</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">B\r\ndegradation, nuclear translocation and\r\nDNA binding stressed by a PI3K-mediated\r\np65 phosphorylation within its TAD upon\r\nIL-1 stimulation (as shown for HepG2\r\ncells</span><span style="font-size: 6.000000pt; font-family: 'ArialMT'; vertical-align: 5.000000pt">162a</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">); whereas IKK</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">? </span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">seems essential\r\nfor I</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">?</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">B</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">? </span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">degradation, IKK</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">? </span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">is required for\r\nPI3K/Akt-dependent p65 phosphorylation\r\n(TAD) and transactivation but dispensable\r\nfor NF-</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">?</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">B liberation (no efficient p65-TAD\r\nphosphorylation, but functional I</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">?</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">B</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">?\r\n</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">degradation in IL-1-treated IKK</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">?</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">-deficient\r\nMEFs; PI3K/Akt pathway does not\r\nparticipate in NF-</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">?</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">B liberation</span><span style="font-size: 6.000000pt; font-family: 'ArialMT'; vertical-align: 5.000000pt">163a</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">);\r\nnevertheless, both IKK</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">? </span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">and -</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">? </span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">(most likely\r\ncomplexed to NEMO) contribute to\r\nPI3K/Akt-mediated NF-</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">?</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">B activation</span><span style="font-size: 6.000000pt; font-family: 'ArialMT'; vertical-align: 5.000000pt">163a </span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">?\r\n</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">IKK</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">? </span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">was shown to phosphorylate p65-\r\nS468 within TAD2 (corresponding to\r\nTAD1-S536) while the latter is bound to\r\nI</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">?</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">B, suggesting multiple IKK sites with\r\nadditive or redundant functions (as shown\r\nfor IL-1-treated Hep3B cells and primary\r\nHSCs (primary human hepatic stellate\r\ncells)</span><span style="font-size: 6.000000pt; font-family: 'ArialMT'; vertical-align: 5.000000pt">157a</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">); IL-1 was also shown to induce\r\nthe positive regulatory p65 phosphorylation\r\nat serine residues by CK2 in HepG2\r\ncells</span><span style="font-size: 6.000000pt; font-family: 'ArialMT'; vertical-align: 5.000000pt">23a </span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">(cytoplasmic CK2:NF-</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">?</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">B interaction\r\ndetectable within 2 ? 5min after IL-1\r\ntreatment), but whether CK2 functions\r\nsynergistically or redundantly has to be\r\nworked out! (p)S276 critical for p65-\r\ndependent IL-6 production in response to\r\nIL-1</span><span style="font-size: 6.000000pt; font-family: 'ArialMT'; vertical-align: 5.000000pt">134a</span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">); necessity of explicit IKK activation\r\n</span><span style="font-size: 10.000000pt; font-family: 'Arial'; font-style: italic">e.g. </span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">via TAK1 or MEKK3 not yet\r\ndemonstrated! </span></p>\r\n </div>\r\n </div>\r\n </div>

<span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt; font-family: ArialMT;">IKK</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt; font-family: ArialMT;">? </span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt; font-family: ArialMT;">and -</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt; font-family: ArialMT;">? </span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt; font-family: ArialMT;">(most likely complexed to NEMO) contribute to PI3K/Akt-mediated NF-</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt; font-family: ArialMT;">?</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt; font-family: ArialMT;">B activation</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 6pt; font-family: ArialMT; vertical-align: 5pt;">163a</span>

<span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt; font-family: ArialMT;">the positive regulatory p65 phosphorylation at serine residues by CK2 in HepG2 cells</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 6pt; font-family: ArialMT; vertical-align: 5pt;">23a </span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt; font-family: ArialMT;">(cytoplasmic CK2:NF-</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt; font-family: ArialMT;">?</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt; font-family: ArialMT;">B interaction detectable within 2 ? 5min after IL-1 treatment), but whether CK2 functions synergistically or redundantly has to be worked out! (p)S276 critical for p65- dependent IL-6 production in response to IL-1</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 6pt; font-family: ArialMT; vertical-align: 5pt;">134a</span><span style="color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt; font-family: ArialMT;">); </span>

S_90 1 S_114 1 S_15 1

\r\n\r\n\r\n\r\n\r\n<p class="p1"><font face="Georgia" size="2">Ap-1 can be activated by atf2, cfos or cjun [1]. </font></p>

<span style="font-family: Georgia; font-size: small;">AP-1 proteins (e.g.  c-Jun, c-Fos, ATF2) form homo- and/or heterodimers via their leucine-zipper domains, and the combination determines the subsequent gene regulation by AP-1 [1,2]. </span>

S_14 1 S_96 1 S_22 1

\r\n \r\n \r\n <div class="page" title="Page 55">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">HGF and uPA are both required for HGF activation [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia" size="2">Pro_hgf is a <span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">HGF precursor necessary for generating the active mature HGF [1,2,3]. </span></font>

<font face="Georgia" size="2">uPA converts pro-HGF to HGF [1,2,3]. </font>

S_42 1 S_85 1

<font face="Georgia" size="2">IKBA is activated by NFKB. IKBA can be deactivated by the presence of IKBA dissolution and IKBA degradation. The joint activity of the negative regulators is dominant over the activator  [1]. </font>

<span style="font-family: Georgia; font-size: small;">IKBa degradation and dissolution inactivates ikba [1,2,3]. </span>

\r\n \r\n \r\n <div class="page" title="Page 47">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">IKBa degradation and dissolution inactivates ikba [1,2,3]. </font></p>\r\n </div>\r\n </div>\r\n </div>

\r\n \r\n \r\n <div class="page" title="Page 47">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">NFKB activates ikba gene expression [1].</font></p>\r\n </div>\r\n </div>\r\n </div>

S_93 1 S_73 1 S_106 1 S_93 1

<font face="Georgia">IKBa can be activated by CK2 or IKBa independently, or by the activity of both IKKAa and nik [1]. </font>

\r\n \r\n \r\n <div class="page" title="Page 46">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia"><span style="font-size: 10pt;">CK2 was found to phosphorylate IK</span><span style="font-size: 10pt;">Ba</span><span style="font-size: 10pt;"> and activate</span><span style="font-size: 10pt;"> its degradation [1,2].</span></font></p>\r\n </div>\r\n </div>\r\n </div>

\r\n \r\n \r\n \r\n <div class="page" title="Page 46">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia"><span style="font-size: 10pt;">Phosphorylation of IK</span><span style="font-size: 10pt;">Ba</span><span style="font-size: 10pt;"> </span><span style="font-size: 10pt;">at S32 and S36 targets it for proteasomal degradation. IKBa must be present to be degraded [1,2].</span></font></p>\r\n </div>\r\n </div>\r\n </div>

\r\n \r\n \r\n <div class="page" title="Page 46">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia"><span style="font-size: 10pt;">IKKaa works with </span><span style="font-size: 10pt;">NIK to phosphorylate IKBa and significantly increases IK</span><span style="font-size: 10pt;">Ba degradation [1,3].</span></font></p>\r\n </div>\r\n </div>\r\n </div>

<span style="font-family: Georgia; font-size: 10pt;">IKKaa works with </span><span style="font-family: Georgia; font-size: 10pt;">NIK to phosphorylate IKBa and significantly increases IK</span><span style="font-family: Georgia; font-size: 10pt;">Ba degradation [1,3].</span>

S_115 1 S_33 1 S_25 1 S_15 1

<font face="Georgia">Mek7 can be activated by mekk3 or tak1_tab [1]. </font>

<span style="color: rgb(79, 79, 79); font-family: Georgia; font-size: 11.818181991577148px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Tak1 induces MEK7 activation by phosphorylation [1,3,4]. </span>

<span style="color: rgb(79, 79, 79); font-family: Georgia; font-size: 11.818181991577148px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Mekk3 directly activates Mek7 by phosphorylation [1,2]. </span>

S_57 1 S_77 1

\r\n \r\n \r\n <div class="page" title="Page 52">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">Elk1 can be activated by erk12, jnk or nuc_p38 [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">P38 and/or JNK phosphorylate and activate Elk-1 [1,2,3]. </font></span>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">ERK1/2 target Elk-1 via the Elk-1 D domain to promote its transcriptional activation [1,4,5]. </font></span>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">P38 and/or JNK phosphorylate and activate Elk-1 [1,2,3]. </font></span>

S_59 1 S_112 1 S_111 1

<font face="Georgia" size="2">Dum_mek3_or_4_or_6_nuc_p38 activates nuc_p38, while MKP1 deactivates nuc_p38 and is dominant over Dum_mek3_or_4_or_6_nuc_p38 [1]. </font>

<div><font face="Georgia" size="2"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">MEK4 performs kinase activity on JNK and p38 by phosphorylating nuclear p38 at T180 and/or Y182 leading to p38 activation and export of p38 to the cytosol. This activity is shown to be induced by IL-1 in HepG2 cells [1,2]. MEK3 and MEK6 also activate p38 [1,3,4]. </span>Relevance of MEK3,4, or 6 in IL-1 signaling pathway is proposed by Ryll et. al. [1]. </font></div>

<div><font size="2" face="Georgia">MKP1 dephosphorylates the kinase activation loop of ERK2, JNK1 and p38 causing deactivation of those factors [1,5,6]. Relevance of MKP1 in IL-1 signaling pathway is proposed by Ryll et. al. [1]. </font></div>

S_67 1 S_117 1

<font face="Georgia">JNK is activated by dum_mek4_or_7_jnk. Mkp1 deactivates JNK and is dominant over dum_mek4_or_7_jnk [1]. </font>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"><font face="Georgia">MEK4 and MEK7 preferentially phosphorylate JNK on Y182 (MEK4) and T180 (MEK7) within its tripeptide dual phosphorylation motif leading to optimal JNK activity. This activity is captured in the dummy node dum_mek4_or_7_jnk [1,3,4,5]. </font></span><span style="font-family: ArialMT; color: rgb(79, 79, 79); line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"> </span>

<span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"><font face="Georgia">MKP1 dephosphorylates and inactivates JNK1 [1,2].</font></span>

S_24 1 S_117 1

\r\n \r\n \r\n <div class="page" title="Page 42">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font size="2" face="Georgia">IKKa and NEMO are both required to activate ikkaa_nemo [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia">NEMO forms dimers with IKKa [1,2,3,4,5,6,7,8]. </font>

<span style="font-family: Georgia;">NEMO forms dimers with IKKa [1,2,3,4,5,6,7,8]. </span>

S_21 1 S_19 1

<font face="Georgia" size="2">Pip3, PDK1, and mTOR2 are all required for activation of akt [1]. </font>

<font face="Georgia" size="2">PDK1, (when bound to PIP<span class="s1">3 </span> at the plasma membrane as Akt) participates in T308 phosphorylation at the activation loop of Akt [1,2]. </font>

<span style="font-family: Georgia; font-size: small;">PDK1, (when bound to PIP</span><span class="s1" style="font-family: Georgia; font-size: small;">3 </span><span style="font-family: Georgia; font-size: small;"> at the plasma </span><span style="font-family: Georgia; font-size: small;">membrane as Akt) participates in</span><span style="font-family: Georgia; font-size: small;"> T308 phosphorylation at the </span><span style="font-family: Georgia; font-size: small;">activation loop of Akt</span><span style="font-family: Georgia; font-size: small;"> [1,2]. </span>

\r\n\r\n\r\n\r\n\r\n\r\n<p class="p1"><font face="Georgia" size="2">IL-1 stimulates Akt phosphorylation and activation involving mTORC2 [1,2]. </font></p>

S_26 1 S_110 1 S_29 1

<font face="Georgia">Dum_ikkab_or_ikkbb_nemo_ikkb_a and dum_tak1_tab_or_mekk3_ikkb_a are both required for activation of ikkb_a [1]. </font>

<font face="Georgia">Activity of NEMO dimers activates ikkb_a [1,2,3,4,5,6,7,8,9].</font>

<font face="Georgia"><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">Active MEKK3 phosphorylates IKKB</span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;"> </span><span style="line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255); font-size: 10pt;">at S177 and S181</span> and activates it [1,2,3,4,5,6,7,8,9].</font>

S_78 1 S_38 1

\r\n \r\n \r\n <div class="page" title="Page 36">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia">MEKK3 or Tak1_tab can each activate mek3 [1]. </font></p><div class="page" title="Page 37" style="font-family: Arial, Verdana;"><div class="layoutArea"><div class="column">\r\n </div>\r\n </div>\r\n </div>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia">Tak1 is a direct activator of mek3 [1,3]. </font>

\r\n \r\n \r\n \r\n <div class="page" title="Page 37">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><span style="font-size: 10pt;"><font face="Georgia">MEKK3 directly phosphorylates and promotes the MEK3 [1,2].</font></span></p>\r\n </div>\r\n </div>\r\n </div>

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<font face="Georgia">Mkp1 is activated by ap1 [1]. </font>

<font face="Georgia">Ap1 increases transcription of mkp1 [1,2,3,4]. </font>

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<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Il1a and Il1b can each activate dum_il1_r1 [1]. </span>

<span style="font-family: Georgia; font-size: small;">Il1b activates the timescale dummy node dum_il1_r1 [1]. </span>

<span style="font-family: Georgia; font-size: small;">Il1a activates the timescale dummy node dum_il1_r1 [1]. </span>

S_101 1 S_7 1