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 2014-01-11T00:01:02Z 2017-05-18T14:36:14Z

<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>

2015-11-15T19:45:45Z

<span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Four and a half LIM domains 1 </font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q13642" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q13642</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/2273" ref="ordinalpos=2&ncbi_uid=2273&link_uid=2273" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">FHL1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">2273</span></font></div>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<font face="Georgia" size="2"><span class="highlight" style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Inositol</span><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"> polyphosphate-5-</span><span class="highlight" style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">phosphatase</span><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">, 145kDa </span></font><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q92835" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q92835</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3635" ref="ordinalpos=3&ncbi_uid=3635&link_uid=3635" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">INPP5D</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">3635</span></font></div>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Protein inhibitor of activated STAT, 1</font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/O75925" style="text-decoration: none; background-color: rgb(255, 255, 255);">O75925</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/8554" ref="ordinalpos=1&ncbi_uid=8554&link_uid=8554" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">PIAS1</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">8554</span></font></div>

2015-11-15T19:45:45Z

<span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Signal-regulatory protein alpha </font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P78324" style="text-decoration: none; background-color: rgb(255, 255, 255);">P78324</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/140885" ref="ordinalpos=2&ncbi_uid=140885&link_uid=140885" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">SIRPA</a><span style="background-color: rgb(255, 255, 255); line-height: 19.999780654907227px;"> </span></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">140885</span></font></div>

2017-05-18T13:35:59Z

\r\n \r\n \r\n \r\n <div class="page" title="Page 64">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">A yet unknown alternative Gab1 tyrosine protein\r\nkinase, located at the plasma membrane [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

2015-11-15T19:45:45Z

<font face="Georgia" size="2"><span class="highlight" style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Protein tyrosine phosphatase</span><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">, non-receptor type 13</span></font><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q12923" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q12923</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/5783" ref="ordinalpos=5&ncbi_uid=5783&link_uid=5783" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">PTPN13</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">5783</span></font></div>

2015-11-15T19:45:45Z

<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>

2017-05-18T13:35:59Z

<span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Protein inhibitor of activated STAT, 3</font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q9Y6X2" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q9Y6X2</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/10401" ref="ordinalpos=1&ncbi_uid=10401&link_uid=10401" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">PIAS3</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">10401</span></font></div>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Membrane-bound gp130 [1].</font></span></div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Interleukin 6 signal transducer (gp130, oncostatin M receptor) </font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P40189" style="text-decoration: none; background-color: rgb(255, 255, 255);">P40189</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3572" ref="ordinalpos=1&ncbi_uid=3572&link_uid=3572" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL6ST</a></font></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 3572</font></span></div>

2015-11-15T19:45:45Z

<span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">PH domain and leucine rich repeat protein phosphatase 1 </font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID:</span><a href="http://www.uniprot.org/uniprot/O60346" style="text-decoration: none; background-color: rgb(255, 255, 255);">O60346</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/23239" ref="ordinalpos=3&ncbi_uid=23239&link_uid=23239" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">PHLPP1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">23239</span></font></div>

2015-11-15T19:45:45Z

<font face="Georgia">Phosphorylated functional il-6 receptor complex [1]: </font><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Interleukin 6 receptor</font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P08887" style="text-decoration: none; background-color: rgb(255, 255, 255);">P08887</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3570" ref="ordinalpos=1&ncbi_uid=3570&link_uid=3570" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL6R</a></font></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 3570</font></span></div></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><br/></font></span></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Interleukin 6 signal transducer (gp130, oncostatin M receptor) </font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P40189" style="text-decoration: none; background-color: rgb(255, 255, 255);">P40189</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3572" ref="ordinalpos=1&ncbi_uid=3572&link_uid=3572" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL6ST</a></font></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 3572</font></span></div></div>

2015-11-15T19:45:45Z

<font style="line-height: normal;" face="Georgia" size="2">This node represents alpha<sub>2</sub>-macroglobulin and gamma fibirnogen [1]. </font><div style="line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Alpha-2-macroglobulin [</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/P01023" style="text-decoration: none; background-color: rgb(255, 255, 255);">P01023</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/2" ref="ordinalpos=2&ncbi_uid=2&link_uid=2" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">A2M</a></font></div><div><span style="line-height: 18.88607406616211px;"><font face="Georgia" size="2">Gene ID: 2</font></span></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Fibrinogen gamma chain [</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/P02679" style="text-decoration: none; background-color: rgb(255, 255, 255);">P02679</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/2266" ref="ordinalpos=6&ncbi_uid=2266&link_uid=2266" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);">FGG</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;">2266</span></font></div>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<font face="Georgia" size="2">Represents Ca<sup>2+</sup>/Calmodulin (CAM- dependent protein kinase 2 or Ca<sup>2+</sup>/Calmodulin (CAM- dependent protein kinase 4 [1]: </font><div><span style="line-height: 19.5px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Calcium/calmodulin-dependent protein kinase II beta</font></span></div><div><font face="Georgia" size="2"><span style="line-height: 19.5px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q13554" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q13554</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.5px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/816" ref="ordinalpos=3&ncbi_uid=816&link_uid=816" style="color: rgb(100, 42, 143); line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">CAMK2B</a></font></div><div><span style="line-height: 19.5px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 816</font></span></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Calcium/calmodulin-dependent protein kinase IV</font></span></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q16566" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q16566</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/814" ref="ordinalpos=2&ncbi_uid=814&link_uid=814" style="color: rgb(100, 42, 143); line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">CAMK4</span></a></font></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 814</font></span></div>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<span style="font-family: Times; font-size: medium; line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Proto-oncogene vav</font></span><div style="font-family: Times; font-size: medium;"><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">UniProt ID: </span><span style="background-color: rgb(255, 255, 255);">P15498</span></font></div><div style="font-family: Times; font-size: medium;"><font face="Georgia" size="2"><span style="background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/7409" ref="ordinalpos=2&ncbi_uid=7409&link_uid=7409" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">VAV1</a></font></div><div style="font-family: Times; font-size: medium;"><font face="Georgia" size="2"><span style="background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">7409</span></font></div>

2015-11-15T19:45:45Z

<font face="Georgia" size="2"><span class="highlight" style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Protein kinase C</span><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">, </span><span class="highlight" style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">delta</span></font><div><font face="Georgia" size="2"><span class="highlight" style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q05655" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q05655</a></font></div><div><font face="Georgia" size="2"><span class="highlight" style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/5580" ref="ordinalpos=1&ncbi_uid=5580&link_uid=5580" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">PRKCD</a><span style="background-color: rgb(255, 255, 255); line-height: 19.999780654907227px;"> </span></font></div><div><font face="Georgia" size="2"><span class="highlight" style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">5580</span></font></div>

2015-11-15T19:45:45Z

<font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">BCL2-associated agonist of cell death [</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/Q92934" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q92934</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/572" ref="ordinalpos=1&ncbi_uid=572&link_uid=572" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">BAD</span></a></font></div><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 572</font></span></div>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<font face="Georgia" size="2">Trans-activated STAT3 (S/Y phosphorylated) [1]. </font><div><div><font face="Georgia" size="2">Signal transducer and activator of transcription 3 (acute-phase response factor) (STAT3)</font></div><div><font face="Georgia" size="2">UniProt Accession ID: <a href="http://www.uniprot.org/uniprot/P40763">P40763</a></font></div><div><font face="Georgia" size="2">Gene Name: STAT3</font></div><div><font face="Georgia" size="2"><font size="2">Gene ID: </font><span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;">6774</span></font></div></div>

2015-11-15T19:45:45Z

<font face="Georgia" size="2">Insulin Receptor </font><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/P06213" style="text-decoration: none; background-color: rgb(255, 255, 255);">P06213</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/3643" ref="ordinalpos=3&ncbi_uid=3643&link_uid=3643" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">INSR</a> </font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">3643</span></font></div>

2015-11-15T19:45:45Z

<div><font size="2" face="Georgia">phospholipase C, gamma 1 (PLCG1)</font></div><div><font face="Georgia" size="2">UniProt Accession ID: <span style="background-color: rgb(255, 255, 255);">P19174</span></font></div><div><font size="2" face="Georgia">Gene Name: PLCG1</font></div><div><font size="2" face="Georgia">NCBI Gene ID: 5535</font></div>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<font face="Georgia"><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>tyrosine-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>

2015-11-15T19:45:45Z

<font face="Georgia" size="2">v-Raf-1 murine leukemia viral oncogene homolog 1</font><div><font face="Georgia" size="2">UniProt ID: <span style="background-color: rgb(255, 255, 255);">P04049</span></font></div><div><font face="Georgia" size="2">Gene Name: RAF1</font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;">5894</span></font></div>

2015-11-15T19:45:45Z

<br/>

2015-11-15T19:45:45Z

<span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase</font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q13233" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q13233</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/4214" ref="ordinalpos=4&ncbi_uid=4214&link_uid=4214" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">MAP3K1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">4214</span></font></div>

2015-11-15T19:45:45Z

<font face="Georgia" size="2">Various hepatic acute-phase plasma protein (APP) gene promoters [1]. </font>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<div style="font-family: Times; font-size: medium;"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Ligand-occupied gp80s [1]. </font></span></div><span style="font-family: Times; font-size: medium; line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Interleukin 6 receptor</font></span><div style="font-family: Times; font-size: medium;"><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P08887" style="text-decoration: none; background-color: rgb(255, 255, 255);">P08887</a></font></div><div style="font-family: Times; font-size: medium;"><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3570" ref="ordinalpos=1&ncbi_uid=3570&link_uid=3570" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL6R</a></font></div><div style="font-family: Times; font-size: medium;"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 3570</font></span></div>

2015-11-15T19:45:45Z

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

2015-11-15T19:45:45Z

<span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">v-myc avian myelocytomatosis viral oncogene homolog</font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID:</span><a href="http://www.uniprot.org/uniprot/P01106" style="text-decoration: none; background-color: rgb(255, 255, 255);">P01106</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name:</span><a href="http://www.ncbi.nlm.nih.gov/gene/4609" ref="ordinalpos=1&ncbi_uid=4609&link_uid=4609" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">MYC</a></font></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 4609</font></span></div>

2015-11-15T19:45:45Z

<div><font face="Georgia" size="2">Y-phosphorylated and homodimerised STAT3 [1]. </font></div><div><font face="Georgia" size="2">Signal transducer and activator of transcription 3 (acute-phase response factor) (STAT3)</font></div><div><font face="Georgia" size="2">UniProt Accession ID: <a href="http://www.uniprot.org/uniprot/P40763">P40763</a></font></div><div><font face="Georgia" size="2">Gene Name: STAT3</font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;">6774</span></font></div>

2015-11-15T19:45:45Z

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

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<font face="Georgia" size="2">Functional il-6 receptor complex [1]: </font><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Interleukin 6 receptor</font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P08887" style="text-decoration: none; background-color: rgb(255, 255, 255);">P08887</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3570" ref="ordinalpos=1&ncbi_uid=3570&link_uid=3570" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL6R</a></font></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 3570</font></span></div></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><br/></font></span></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Interleukin 6 signal transducer (gp130, oncostatin M receptor) </font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P40189" style="text-decoration: none; background-color: rgb(255, 255, 255);">P40189</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3572" ref="ordinalpos=1&ncbi_uid=3572&link_uid=3572" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL6ST</a></font></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 3572</font></span></div></div>

2015-11-15T19:45:45Z

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

2015-11-15T19:45:45Z

<font face="Georgia" size="2">Complex between Grb2 and SOS [1]. </font><div><font face="Georgia" style="background-color: rgb(255, 255, 255);" size="2">Growth factor receptor-bound protein 2</font><div><font face="Georgia" style="background-color: rgb(255, 255, 255);"><font size="2">UniProt Accession ID: </font><font size="2">Q60631</font></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/2885" ref="ordinalpos=1&ncbi_uid=2885&link_uid=2885" style="line-height: 18.88888931274414px; white-space: nowrap;"><span class="highlight">GRB2</span></a></font></div><div><font size="2" face="Georgia" style="background-color: rgb(255, 255, 255);">Gene ID: 2885</font></div></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Son of sevenless homolog 1 </font></span></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q07889" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q07889</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/6654" ref="ordinalpos=5&ncbi_uid=6654&link_uid=6654" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">SOS1</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">6654</span></font></div>

2015-11-15T19:45:45Z

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

2015-11-15T19:45:45Z

<span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Caspase 9, apoptosis-related cysteine peptidase</font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P55211" style="text-decoration: none; background-color: rgb(255, 255, 255);">P55211</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/842" ref="ordinalpos=1&ncbi_uid=842&link_uid=842" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">CASP9</span></a></font></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 842</font></span></div>

2015-11-15T19:45:45Z

<font face="Georgia" size="2">Fully activated shp2 [1]. </font><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Protein tyrosine phosphatase, non-receptor type 11</font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px;">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q06124" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q06124</a><span style="line-height: 19.999780654907227px;"><br/></span></font><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/5781" ref="ordinalpos=1&ncbi_uid=5781&link_uid=5781" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">PTPN11</a></font></div><div><font face="Georgia" size="2"><font size="2">Gene ID: </font><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">5781</span></font></div></div></div>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<div style="font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font face="Georgia" size="2">Ras-like Protein</font></div><div style="font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font face="Georgia" size="2">UniProt Accession ID: <a href="http://www.uniprot.org/uniprot/P0CQ42">P0CQ42</a></font></div><div style="font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font face="Georgia" size="2"><br/></font></div><div style="font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font face="Georgia" size="2">v-Ha-ras Harvey rat sarcoma viral oncogene homolog (HRAS)</font></div><div style="font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font face="Georgia" size="2">Rat:</font></div><div style="font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font face="Georgia" size="2">UniProt Accession ID: P20171</font></div><div style="font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font size="2" face="Georgia">Human:</font></div><div style="font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font size="2" face="Georgia">UniProt Accession ID: P01112</font></div><div style="font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font size="2" face="Georgia">Gene Name: HRAS</font></div><div style="font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); color: rgb(87, 87, 87); line-height: 16.78819465637207px; white-space: nowrap;">3265</span></font></div><div style="font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font face="Georgia" size="2"><br/></font></div><div><span style="font-weight: normal;"><font face="Georgia" size="2">Kirsten rat sarcoma viral oncogene homolog (KRAS)</font></span></div><div><font face="Georgia" size="2"><span style="font-weight: normal;">UniProt ID: </span><strong style="background-color: rgb(255, 255, 255);">P01116</strong></font></div><div><span style="font-weight: normal;"><font face="Georgia" size="2">Gene Name: KRAS</font></span></div><div><font face="Georgia" size="2"><span style="font-weight: normal;">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;">3845</span></font></div><div><font face="Georgia" size="2"><span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;"><br/></span></font></div><div>NRAS = neuroblastoma RAS viral (v-ras) oncogene homolog </div><div>UniProt ID: <a href="http://www.uniprot.org/uniprot/P01111" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">P01111</a></div><div>Gene Name: NRAS</div><div>Gene ID: <span style="color: rgb(87, 87, 87); font-family: arial, helvetica, clean, sans-serif; font-size: 11.6999998092651px; line-height: 16.199821472168px; background-color: rgb(213, 222, 227);">4893</span></div>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<span style="font-family: Georgia; font-size: small;">Trans-activated STAT1 (S/Y phosphorylated) [1]. </span><div><span style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Signal transducer and activator of transcription 1</font></span><div><font face="Georgia" size="2"><span style="line-height: 15.989583969116211px;">Uniport ID: </span><a href="http://www.uniprot.org/uniprot/P42224">P42224</a><span style="line-height: 15.989583969116211px;"><br/></span></font><div><span style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene Name: STAT1 </font></span></div></div><div><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 16.78819465637207px; white-space: nowrap;">6772</span></font></div></div>

2015-11-15T19:45:45Z

<font face="Georgia" size="2">Calcium- Calmodulin complex [1]. </font><div><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"><span id="parentSpecies:viewSpeciesDescription">Calcium Ion, </span><span style="line-height: 14.390625px;">PubChem ID: </span><a name="cid2entrez" href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pccompound&term=271[uid]" style="outline: 0px; border: 0px; line-height: 19px; vertical-align: baseline; margin: 0px; padding: 0px; text-decoration: none;">271</a></font></p><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"><span style="line-height: 19.999780654907227px; orphans: auto; widows: auto;">Calmodulin 1, UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P62158" style="line-height: normal; text-decoration: none;">P62158</a>, Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/801" ref="ordinalpos=1&ncbi_uid=801&link_uid=801" style="line-height: 19.999780654907227px; white-space: nowrap;">CALM1</a>, Gene ID: 801</font></p></div>

2015-11-15T19:45:45Z

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

2015-11-15T19:45:45Z

<span style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Forkhead box protein O1</font></span><div><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">UniProt ID: </span><span style="background-color: rgb(255, 255, 255);">Q12778</span></font></div><div><font size="2" face="Georgia"><span style="background-color: rgb(255, 255, 255);">Gene Name:</span><a href="http://www.ncbi.nlm.nih.gov/gene/2308" ref="ordinalpos=1&ncbi_uid=2308&link_uid=2308" style="background-color: rgb(255, 255, 255); line-height: 19.999780654907227px; white-space: nowrap; color: rgb(100, 42, 143);">FOXO1</a></font></div><div><font face="Georgia" size="2"><span style="background-color: rgb(255, 255, 255);">Gene ID: 2308</span></font></div>

2015-11-15T19:45:45Z

<font face="Georgia">RAS p21 protein activator</font><div><font face="Georgia" size="2"><em>also known as:</em> Ras GTPase-activating protein 1</font></div><div><font face="Georgia" size="2">UniProt ID: <span style="background-color: rgb(255, 255, 255);">P20936</span></font></div><div><font face="Georgia" size="2">Gene Name: RASA1</font></div><div><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 18.88888931274414px;">5921</span></font></div>

2015-11-15T19:45:45Z

<span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Protein tyrosine phosphatase, non-receptor type 11</font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px;">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q06124" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q06124</a><span style="line-height: 19.999780654907227px;"><br/></span></font><div style="line-height: normal;"><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/5781" ref="ordinalpos=1&ncbi_uid=5781&link_uid=5781" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">PTPN11</a></font></div><div style="line-height: normal;"><font face="Georgia" size="2">Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">5781</span></font></div></div>

2017-05-18T13:35:59Z

<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>

2015-11-15T19:45:45Z

<p style="orphans: 3; widows: 3; line-height: 1.5em; margin: 0.4em 0px 0.5em; color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; background-color: rgb(255, 255, 255);"><span id="parentSpecies:viewSpeciesDescription">Calcium Ion</span></p><div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.390625px; background-color: rgb(255, 255, 255);">PubChem ID: <a name="cid2entrez" href="http://www.ncbi.nlm.nih.gov/sites/entrez?cmd=search&db=pccompound&term=271[uid]" style="outline: 0px; color: rgb(0, 153, 78); border: 0px; font-family: Arial, Verdana, sans-serif; font-size: 14px; line-height: 19px; vertical-align: baseline; margin: 0px; padding: 0px; text-decoration: none;">271</a></div>

2015-11-15T19:45:45Z

<font face="Georgia" size="2">IL-6-induced proliferation facilitates liver regeneration [1]. </font>

2015-11-15T19:45:45Z

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

2015-11-15T19:45:45Z

<font face="Georgia" size="2">There are three forms of IP3:</font><div><ul><li><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Inositol-trisphosphate 3-kinase A, UniProt ID: </span><span style="background-color: rgb(255, 255, 255);">P23677 (activated by calmodulin [3]). </span></font></li><li><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Inositol-trisphosphate 3-kinase B, </span><span style="background-color: rgb(255, 255, 255); line-height: 16px;">UniProt ID: </span><span style="background-color: rgb(255, 255, 255);">P27987</span><span style="background-color: rgb(255, 255, 255); line-height: 16px;">  (more sensitive, by 8-fold, to calmodulin than isoform A [4])</span></font></li><li><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Inositol-trisphosphate 3-kinase C, UniProt ID: </span><span style="background-color: rgb(255, 255, 255);">Q96DU7 (activated by calmodulin like IP3A [2], but localized and expressed h</span><span style="background-color: rgb(255, 255, 255); line-height: 16px;">ighly in pancreas, skeletal muscle, liver, placenta and weakly in kidney and brain [2].</span><span style="background-color: rgb(255, 255, 255);"> </span><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Shuttles actively between nucleus and cytoplasm with both nuclear import and nuclear export activity. [1])</span></font></li></ul></div><div><font face="Georgia" size="2"><span style="background-color: rgb(255, 255, 255);">In EGFR ErbB Signaling  and IL-6 models, this node represents the molecule i</span>nositol-1,4,5-triphosphate (PubChem ID:<span style="color: rgb(85, 85, 85); 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=439456[uid]" style="border: 0px; outline: 0px; line-height: 19px; vertical-align: baseline; margin: 0px; padding: 0px; text-decoration: none; color: rgb(0, 86, 204); background-color: rgb(255, 255, 255);">439456</a>) and not the kinase [5,6]. </font></div>\r\n \r\n \r\n \r\n <div class="page" title="Page 2">\r\n <div class="section">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><span style="font-size: 10.000000pt; font-family: 'Helvetica'"> <br/></span></p>\r\n </div>\r\n </div>\r\n </div>\r\n </div>

2015-11-15T19:45:45Z

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

2015-11-15T19:45:45Z

<font face="Georgia"><span class="highlight" style="font-size: 13.333333969116211px; line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">C-reactive protein</span><span style="font-size: 13.333333969116211px; line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">, pentraxin-related</span></font><div><font face="Georgia"><span style="font-size: 13.333333969116211px; line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P02741" style="font-size: small; text-decoration: none; background-color: rgb(255, 255, 255);">P02741</a></font></div><div><font face="Georgia"><span style="font-size: 13.333333969116211px; line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/1401" ref="ordinalpos=1&ncbi_uid=1401&link_uid=1401" style="font-size: 13.333333969116211px; line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">CRP</a></font></div><div><span style="font-size: 13.333333969116211px; line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia">Gene ID: 1401</font></span></div><div style="font-family: Arial, Verdana;"><span style="font-family: arial, helvetica, clean, sans-serif; font-size: 13.333333969116211px; line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><br/></span></div>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

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

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<font face="Georgia" size="2">Y-phosphorylated and homodimerised STAT1 [1].</font><div><span style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Signal transducer and activator of transcription 1</font></span><div><font face="Georgia" size="2"><span style="line-height: 15.989583969116211px;">Uniport ID: </span><a href="http://www.uniprot.org/uniprot/P42224">P42224</a><span style="line-height: 15.989583969116211px;"><br/></span></font><div><span style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene Name: STAT1 </font></span></div></div><div><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 16.78819465637207px; white-space: nowrap;">6772</span></font></div></div>

2015-11-15T19:45:45Z

<font face="Georgia" size="2">mTOR complex 1 consisting of mTOR, mLST8, RAPTOR and DEPTOR [1]: </font><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"><br/></font></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">MTOR associated protein, LST8 homolog </font></span></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; 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: 19.999780654907227px; 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: 19.999780654907227px; 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: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">64223</span></font></div><div><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;"><font face="Georgia" size="2"><br/></font></span></div><div><div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Regulatory associated protein of MTOR, complex 1</font></span></div><div><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q8N122" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q8N122</a></font></div><div><font face="Georgia" size="2">Gene Name: <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/57521" ref="ordinalpos=1&ncbi_uid=57521&link_uid=57521">RPTOR</a></span> </font></div><div><font face="Georgia" size="2">Gene ID: 57521</font></div></div><div><font face="Georgia" size="2"><br/></font></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">DEP domain containing MTOR-interacting protein</font></span></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; 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: 19.999780654907227px; 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: 19.999780654907227px; 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: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">64798</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: 19.999780654907227px; background-color: rgb(255, 255, 255);"><br/></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: 19.999780654907227px; background-color: rgb(255, 255, 255);"><br/></span></div>

2015-11-15T19:45:45Z

<div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Soluble GP130 [1].</font></span></div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Interleukin 6 signal transducer (gp130, oncostatin M receptor) </font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P40189" style="text-decoration: none; background-color: rgb(255, 255, 255);">P40189</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3572" ref="ordinalpos=1&ncbi_uid=3572&link_uid=3572" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL6ST</a></font></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 3572</font></span></div>

2015-11-15T19:45:45Z

<div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Ligand-occupied gp80m [1]. </font></span></div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Interleukin 6 receptor</font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P08887" style="text-decoration: none; background-color: rgb(255, 255, 255);">P08887</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3570" ref="ordinalpos=1&ncbi_uid=3570&link_uid=3570" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">IL6R</a></font></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 3570</font></span></div>

2015-11-15T19:45:45Z

<font face="Georgia" size="2">Counteraction of apoptosis [1]. </font>

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

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

2015-11-15T19:45:45Z

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

2015-11-15T19:45:45Z

<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>

2015-11-15T19:45:45Z

<span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">GRB2-associated binding protein 1</font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID : </span><a href="http://www.uniprot.org/uniprot/Q13480" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q13480</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/2549" ref="ordinalpos=1&ncbi_uid=2549&link_uid=2549" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">GAB1</span></a></font></div><div><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 2549</font></span></div>

2015-11-15T19:45:45Z

<font face="Georgia"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Ribosomal protein S6 kinase, 70kDa, polypeptide 1</span><br/></font><div><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">UniProt ID: </span><span style="background-color: rgb(255, 255, 255);">P23443</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><a href="http://www.ncbi.nlm.nih.gov/gene/6198" ref="ordinalpos=2&ncbi_uid=6198&link_uid=6198" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">RPS6KB1</a></font></div><div><font face="Georgia" size="2"><span style="background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">6198</span></font></div>

2015-11-15T19:45:45Z

<div><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Ras-related C3 botulinum toxin substrate 1 </font></span></div><div><font face="Georgia" size="2"><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">(rho family, </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">small</span><span style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);"> GTP binding protein </span><span class="highlight" style="line-height: 18.88888931274414px; background-color: rgb(255, 255, 255);">Rac1</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><font face="Georgia" size="2">UniProt ID: <a href="http://www.uniprot.org/uniprot/P63000" style="text-decoration: none; background-color: rgb(255, 255, 255);">P63000</a></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/5879" ref="ordinalpos=1&ncbi_uid=5879&link_uid=5879" style="line-height: 18.88888931274414px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">RAC1</span></a></font></div><div><font face="Georgia" size="2">Gene ID: 5879</font></div>

2015-11-15T19:45:45Z

<font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Mitogen-activated protein kinase 14 </span><br/></font><div><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">UniProt ID: </span><span style="background-color: rgb(255, 255, 255);">Q16539</span></font></div><div><font face="Georgia" size="2"><span style="background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/1432" ref="ordinalpos=1&ncbi_uid=1432&link_uid=1432" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">MAPK14</a></font></div><div><font face="Georgia" size="2"><span style="background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">1432</span></font></div>

2015-11-15T19:45:45Z

<div><font face="Georgia" size="2"><span class="highlight" style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Janus</span><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">kinase</span><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"> </span><span class="highlight" style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">1</span></font></div><font face="Georgia" size="2">Uniprot ID: <a href="http://www.uniprot.org/uniprot/P23458" style="text-decoration: none; background-color: rgb(255, 255, 255);">P23458</a></font><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/3716" ref="ordinalpos=2&ncbi_uid=3716&link_uid=3716" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">JAK1</a></font></div><div><font face="Georgia" size="2">Gene ID: 3716</font></div>

2015-11-15T19:45:45Z

<div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Y-phosphorylated Gab1 (membrane- bound) [1].</span></font></div><span style="font-family: Arial, Verdana; font-size: 10pt; line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">GRB2-associated binding protein 1</font></span><div style="font-family: Arial, Verdana; font-size: 10pt; line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID : </span><a href="http://www.uniprot.org/uniprot/Q13480" style="text-decoration: none; background-color: rgb(255, 255, 255);">Q13480</a></font></div><div style="font-family: Arial, Verdana; font-size: 10pt; line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/2549" ref="ordinalpos=1&ncbi_uid=2549&link_uid=2549" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">GAB1</span></a></font></div><div style="font-family: Arial, Verdana; font-size: 10pt; line-height: normal;"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene ID: 2549</font></span></div>

2015-11-15T19:45:45Z

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

2015-11-15T19:45:45Z

<span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">jun B proto-oncogene</font></span><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P17275" style="text-decoration: none; background-color: rgb(255, 255, 255);">P17275</a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/3726" ref="ordinalpos=2&ncbi_uid=3726&link_uid=3726" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);"><span class="highlight">JUNB</span></a></font></div><div><font face="Georgia" size="2"><span style="line-height: 19.999780654907227px; background-color: rgb(255, 255, 255);">Gene ID: </span><span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">3726</span></font></div>

2015-11-15T19:45:45Z

<font face="Georgia" size="2">IL6rc and jak1 are both required to activate il6rc_p. Shp2 and shp2_a are both inhibitors of il6rc_p and are both dominant over the activators [1]. </font>

<font face="Georgia" size="2">SHP2 binds tyrosine 759 on  the IL-6 receptor complex and stops its activity [1,4,5]. </font>

<span style="font-family: Georgia; font-size: small;">The IL6 receptor must be present to be phosphorylated by JAK1 as shown in IL-6 treated COS and HepG2 cells [1,2,3]. </span>

<font face="Georgia" size="2">The IL6 receptor must be present to be phosphorylated by JAK1 as shown in IL-6 treated COS and HepG2 cells [1,2,3]. </font>

<span style="font-family: Georgia; font-size: small;">SHP2 binds tyrosine 759 on  the IL-6 receptor complex and stops its activity [1,4,5]. </span>

S_35 1 S_82 1 S_54 1 S_42 1

<font face="Georgia" size="2">Stat3_ta activates a2m_gfbg, while nfkb deactivates s2m_gfbg and is dominant over Stat3_ta [1]. </font>

<font size="2" face="Georgia">Active NF-KB suppresses gamma FBG expression in repose to IL-6 as shown in HEPG2 cells [1,2].  IL-1 activated NF-KB has been shown to suppress gamma FBG expression in HepG2 cells and in human primary hepatocytes (thought to be by inhibiting STAT3 activation) [1,2]. <span style="font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;">NF-KB p50/p65 heterodimer competes with STAT3 to bind the a2m promoter and inhibits a2M gene expression in response to IL-6 as shown in HepG2 [1,3]. </span></font>

<font face="Georgia" size="2"><font size="2">NF-KB p50/p65 heterodimer competes with STAT3 to bind the a2m promoter and </font>inhibits<font size="2"> a2M gene expression in response to IL-6 as shown in HepG2 [1,3]. STAT3 works with cyclin-dependent kinase 9 to trigger gamma FBG expression in reponse to IL-6 as shown in HepG2 [1,4]. </font></font>

S_13 1 S_67 1

<font face="Georgia" size="2">IL-6rc_p activated mek6 [1]. </font>

<font face="Georgia" size="2">IL-6 induces p38 activation by MEK6 as shown in HepG2 cells [1,2,3]. </font>

S_1 1

<font face="Georgia" size="2">Cam_ca activates camk24 [1]. </font>

<font face="Georgia" size="2">Calcium/calmodulin complex stops the auto-inhibition of CaMK [1,2]. </font>

S_50 1

<font face="Georgia" size="2">Stat3_ta activates cebpd [1]. </font>

<font face="Georgia" size="2">STAT3 causes activation of CEBPD gene in human hepatoma cells by interacting with the APR element of the promoter [1,2,3]. </font>

S_13 1

<font face="Georgia" size="2">Dum_il6rc_p_or_grb2_vav is activated by vav and inhibited by SOCS1 [1]. </font>

<font face="Georgia" size="2">Gp130's membrane distal region and Vav/Grb2 complex cause VAV phosphorylation as shown in human myeloma B-cell line U266 [1,2,3]. </font>

<font face="Georgia" size="2">SOCS1 recruits VAV for ubiquitin-mediated protein degradation as shown in COS-7 cels [1,4]. </font>

S_60 1 S_34 1

<font face="Georgia" size="2">MEK4 activates PCKD [1]. </font>

<font face="Georgia" size="2">MEK4 phosphorylates PKC delta at T505 as shown in HepG2 cells and thereby activates PCKD [1,2,3]. </font>

S_26 1

<font size="2" face="Georgia">Akt inhibits BAD [1]. </font>

<font face="Georgia" size="2">Akt phosphorylates and inactivates BAD after IL-6 treatment in human multiple myeloma cells [1,2,3]. </font>

S_21 1 S_21 1

<font size="2" face="Georgia">P38 or Stat3_ta can each independently activate cebpb [1]. </font>

<font face="Georgia" size="2">p38 is essential for C/EBPB expression after IL-6 treatment as shown in RAW264.7 cells (murine macrophages) in response to LPS [1,2,3]. </font>

<font face="Georgia" size="2">STAT3 up regulates C/EBPB expression in murine hepatocytes and HepG2 cells [1,4,5]. </font>

S_13 1 S_81 1

<font size="2" face="Georgia">Stat3_ta is activated by the joint activity of dum_mtorc1_or_pkcd_stat3_ta and stat3_py. Pias3 and slim are each negative regulators of stat3_ta and are both dominant over the activators [1]. </font>

<span style="font-family: Georgia; font-size: small;">Y phosphorylation of STAT3  as shown in IFNa treated HEK293T cells is required for activation [1,7,8,9,10,11]. </span>

<font face="Georgia" size="2">PCKdelta or mTOR cause STAT3 S727 phosphorylation which leads to activation [1,2,3,4]. </font>

<font face="Georgia" size="2">SLIM causes ubiquitination/proteasome-dependent degradation of STATs and impairs the Y phosphorylation of STAT4  as shown in IFNa treated HEK293T cells [1,10,11]. </font>

<font face="Georgia" size="2">PIAS3 interacts with STAT3 in IL-6 treated HepG2, M1 and MCF7 cells and inhibits STAT3 [1,5,6]. </font>

S_38 1 S_31 1 S_5 1 S_61 1

<font face="Georgia" size="2">SOCS1 and SOCS3 are both negative regulators of IR [1]. </font>

<font face="Georgia" size="2">SOCS1 does not affect autophosphorylation and needs insulin for maximal IR affinity as shown in insulin-treated HepG2 cells [1,4]. </font>

<font face="Georgia" size="2">SOCS3 inhibits the hepatic insulin receptor as shown in HepG2 cells and murine liver. SOCS3 may induce receptor autophosphorylation or out compete insulin receptor substrate [1,2,3]. </font>

S_34 1 S_76 1 S_34 1 S_76 1

<font face="Georgia" size="2">Gab1_mem_p activates PLCg [1]. </font>

<font face="Georgia" size="2">Phosphorylated Gab1 binds and activates PLCg as shown in HGF-treated HEK293 cells [1,2]. </font>

S_83 1

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

<font face="Georgia" size="2">PI3K phosphorylates PIP2 and yields PIP3 [1,2]. </font>

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

S_63 1 S_74 1

<font size="2" face="Georgia">IRS1_py is negatively inhibited by irs1_ps, shp2, and shp2_a. Each negative inhibitor is sufficient to deactivate irs1_py [1]. </font>

<font face="Georgia" size="2">SHP2 dephosphorylates tyrosine residues on IRS1 as shown in insulin-treated CHO cells [1,3]. </font>

<font face="Georgia" size="2">IRS1 S/T phosphorylation interferes with IR-mediated phosphorylation of IRS1 [1,2]. </font>

<span style="font-family: Georgia; font-size: small;">SHP2 dephosphorylates tyrosine residues on IRS1 as shown in insulin-treated CHO cells [1,3]. </span>

S_42 1 S_45 1 S_54 1 S_54 1 S_45 1 S_42 1

<font face="Georgia" size="2">Ras activates Raf1 [1]. </font>

<font face="Georgia" size="2">GTP-RAS activates Raf1 by binding and causing conformational changes that expose Raf1's kinase domain as shown in HeLa cells in response to IFNB and oncostatin M or Il-6 treated AF-10 cells [1,2,3,4]. </font>

S_47 1

<font face="Georgia" size="2">PDK1, mTORC2 and PIP3 are all required to activate Akt. PHLPP and SHIP are both inhibitors of Akt and are dominant over the activators [1]. </font>

<font face="Georgia" size="2">PDK1 phosphorylates T308 in the activation loop of Akt and activates it [1,2]. </font>

<font face="Georgia" size="2">PIP3 binds Akt and PDK1 when PDK1 phosphorylates Akt [1,2]. </font>

<font face="Georgia" size="2">mTORC2 phosphorylates S473 Akt and activates it [1,2]. </font>

<font face="Georgia" size="2">SHIP inhibits Akt [1,4]. </font>

<font face="Georgia" size="2">PHLPP dephosphorylates and deactivates Akt at S473 [1,3]. </font>

S_20 1 S_17 1 S_65 1 S_85 1 S_14 1

<font face="Georgia" size="2">Rac1 activates Mekk1 [1]. </font>

<font face="Georgia" size="2">GTP bound Rac1 binds MEKK1 and becomes activated in HepG2 cells [1,2,3].</font>

S_80 1

<font face="Georgia" size="2">CEBPB or CEBPD can each independently activate var_app [1]. </font>

<span style="font-family: Georgia; font-size: small;">CEBPB interacts with promoters as shown in HepG2 cells [1,2,3,4]. </span>

<font face="Georgia" size="2">CEBPD interacts with promoters as shown in HepG2 cells [1,2,3,4]. </font>

S_11 1 S_7 1

<font face="Georgia" size="2">Akt inhibits gsk3 [1].</font>

<font face="Georgia" size="2">Akt phosphorylates GSK3B and inactivates it as shown in IL-6 treated in human multiple myeloma MM.1S cells [1,2,3]. </font>

S_21 1 S_21 1

<font face="Georgia" size="2">Mekk1 activates mek4 [1]. </font>

<font face="Georgia" size="2">MEKK1 activates MEK4 by phosphorylating T223 in HepG2 cells [1,2,3]. </font>

S_23 1

<font face="Georgia" size="2">STAT3 activates cFos [1]. </font>

<font face="Georgia" size="2">STAT3 causes c-Fos gene expression as shown in murine hepatocytes and HepG2 cells [1,2,3]. </font>

S_13 1

<font face="Georgia" size="2">IL6 activates gp80s_a. Gp130s is a negative regulator of gp80s_a and is dominant over IL6 [1]. </font>

<font face="Georgia" size="2">IL-6 binds and activates the IL-6/gp80 soluble alpha-receptor complex [1,2]. </font>

<font face="Georgia" size="2">Soluble gp130 competes with the IL-6/gp80 complex as shown in IL-6 treated HepG2 cells [1,3]. </font>

S_4 1 S_69 1

<font face="Georgia" size="2">Shp2 or shp2_a can each individually activate tdum_shp2_il6rc_p [1] .</font>

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

S_54 1 S_42 1

<font face="Georgia" size="2">STAT3 activates cMYC [1]. </font>

<font face="Georgia" size="2">STAT3 binds the c-MYC promoter and and up-regulates the c-MYC gene as shown in HepG2 cells [1,2]. </font>

S_13 1

<font face="Georgia" size="2">IL6rc_p and JAK1 are both required to activate stat3_py. Cyt_ptpe, SHP2, and SHP2_a are all inhibitors of stat3_py and are dominant over the activators [1]. </font>

<font face="Georgia" size="2">SHP2 may dephosphorylate STAT3 and inactivate it [1,7,11]. </font>

<font face="Georgia" size="2">JAK1 phosphorylates STAT3-Y705 [1,5]. </font>

<font face="Georgia" size="2">IL6rc_p binds STAT3 at phosphorylated Y767, Y814, Y905 or Y915 at its SH2 domain [1,2,3]. </font>

<font face="Georgia" size="2">cyt-PTPe inhibits STAT3- Y phosphorylation as shown in IL-6 treated murine M1 myeloid cells [1,10]. </font>

<font face="Georgia" size="2">SHP2_a bound to STAT1 interaction in IFN-treated HEK293T and EGF-treated A431 cells [1,8]. </font>

S_1 1 S_82 1 S_44 1 S_42 1 S_54 1

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Camk24 or pkcd can each independently activate dum_pkcd_camk24_stat1_ta [1]. </span>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Camk24 activates the timescale dummy node dum_pkcd_camk24_stat1_ta [1]. </span>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">pkcd activates the timescale dummy node dum_pkcd_camk24_stat1_ta [1]. </span>

S_9 1 S_6 1

<font face="Georgia" size="2">Mek1 activates erk12 [1]. </font>

<font face="Georgia" size="2">ERK1 is phosphorylated at T202/Y204 in a Ras-dependent activation via MEK1 and Gab1:SHP2 complex as shown in HepG2 cells [1,2,3,4]. Ryll et. al. proposed relevance of MEK1 in IL-6 signaling [1]. </font>

S_72 1

<font face="Georgia" size="2">Stat3_ta activates SOCS1 [1]. </font>

<font face="Georgia" size="2">Stat3_ta stimulates SOCS genes as shown in IL-6 treated M1 cells [1,2,3]. </font>

S_13 1

<font face="Georgia" size="2">Gp130m and dum_gp80_a_il6rc are both required for activation of il6rc [1]. </font>

<span style="font-family: Georgia; font-size: small;">Gp130m binds the gp80soluble/il6 alpha-receptor complex as shown in IL-6 treated Hep3B cells [1,2]. </span>

S_77 1 S_73 1

<font face="Georgia" size="2">Socs1 activates tdum_socs1_vav [1]. </font>

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

S_34 1

<font face="Georgia" size="2">SHP2 and il6rc_p can each independently activate grb2_sos [1]. </font>

<font face="Georgia" size="2">SHP2 binds Grb2 at its SH2 domain and links SOS via its SH3 domain [1,2,3]. </font>

<font face="Georgia" size="2">Ras activation of Grb2/SOS can occur in a SHP2-independent manner as shown by phosphorylated EGFR/Grb2 interaction in Vero cells and MEFs [1,4,5]. </font>

S_1 1 S_54 1

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Mtorc1 or pkcd can each independently activate dum_mtorc1_or_pkcd_stat3_ta [1]. </span>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Mtorc1 activates the timescale dummy node dum_mtorc1_or_pkcd_stat3_ta [1]. </span>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Pkcd activates the timescale dummy node dum_mtorc1_or_pkcd_stat3_ta [1]. </span>

S_68 1 S_9 1

<font face="Georgia" size="2">Akt is a negative regulator of CASP9 [1]. </font>

<font face="Georgia" size="2">Akt phosphorylates and blocks caspase 9 protease activity after IL-6 treatment as shown in human multiple myeloma cells [1,2,3]. </font>

S_21 1 S_21 1

<font face="Georgia" size="2">Gab1_mem_p and shp2 are both required to activate shp2_a. ROS and sirp1a are both negative regulators and are both dominant over the positive regulators [1]. </font>

<font face="Georgia" size="2">SIRP1 associates with SHP2 and inhibits its activation as shown in IL-6 simulated MEFs [1,7]. </font>

<font face="Georgia" size="2">Interaction of SHP2 and Gab1 targets SHP2 to the membrane and causes full activation of SHP2 as shown in overexpression studies in COS-7 cells [1,2,3,4,5].</font>

<font face="Georgia" size="2">ROS inhibit SHP by oxidizing its catalytic cysteine as shown in hepatic live tumourigenesis [1,8,9]. </font>

<span style="font-family: Georgia; font-size: small;">Interaction of SHP2 and Gab1 targets SHP2 to the membrane and causes full activation of SHP2 as shown in overexpression studies in COS-7 cells [1,2,3,4,5].</span>

S_83 1 S_54 1 S_46 1 S_39 1

<font face="Georgia" size="2">Mk2 is activated by p38 [1]. </font>

<font face="Georgia" size="2">p38 phosphorylates mk2 at T222, S272 and T334 and activates it as shown in IL-6 treated HepG2 cells [1,2,3,4,5,6]. </font>

S_81 1

<font face="Georgia" size="2">ERK12 and pckd can each independently activate irs1_ps [1]. </font>

<font face="Georgia" size="2">ERK1/2 inhibits IRS1 by phosphorylating S307 [1,4,5], or by impairing IP-mediated IRS1-Y phosphorylation by phosphorylating S616 as shown in IL-6 treated human umbilical vein endothelial cells [1,6]. </font>

<font face="Georgia" size="2">PCK delta induces IRS1 phosphorylation of S24 in the IRS1 PH domain that interferes with PIP2 as shown in PMA-treated H4IIE rat hepatoma cells [1,2]. PCK delta also may phosphorylate S312, S636/639 and S616 by activating S/T kinases as shown in TNFs treated H4IIE rat hepatoma cells [1,3]. </font>

S_33 1 S_9 1

<font face="Georgia" size="2">Grb2_sos activates Ras, while ras_gap inhibits Ras and is dominant over grb2_sos [1]. </font>

<font face="Georgia" size="2">Grb2 bound SOS activates Ras [1,2]. </font>

<font face="Georgia" size="2">RasGAP inhibits Ras by turning on its GTPase activity as shown in EGF-treated Vero cells [1,3,4]. </font>

S_37 1 S_53 1

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

<font face="Georgia" size="2">C/EBPB activates the hgf promoter as shown in IL-6 or TNFa murine NIH 3t3 fibroblasts [1,2]. </font>

<span style="font-family: Georgia; font-size: small;">C/EBPD activates the hgf promoter as shown in IL-6 or TNFa murine NIH 3t3 fibroblasts [1,2]. </span>

S_11 1 S_7 1

<font size="2" face="Georgia">Dum_pkcd_camk24_stat1_ta and stat1_py are both required for activation of stat1_ta. PIAS1 and SLIM are both inhibitors of stat1_ta both are dominant over the activators [1]. </font>

<font face="Georgia" size="2">PIAS1 associates with STAT1 when it is phosphorylated at Y701 and inhibits STAT1's DNA binding activity as shown in IL-6 treated HepG2 cells [1,8,9,10]. </font>

<font face="Georgia" size="2">STAT1 phosphorylated at S727 and PKCd is required for activation of stat1_ta as shown in IFNa treated Molt-4 and U-266 cells [1,2,3,4], but not observed in IL-6 treated HepG2, PC12 or A431 cells [1,5]. CaMKII phosphorylates STAT1 at S727 in NIH 3t3 cells after treatment with IFN [1,7]. </font>

<span style="font-family: Georgia; font-size: small;">PIAS1 associates with STAT1 when it is phosphorylated at Y701 and inhibits STAT1's DNA binding activity as shown in IL-6 treated HepG2 cells [1,8,9,10]. </span>

<font face="Georgia" size="2">SLIM induces ubiquitination and proteasome-dependent degradation of STAT1/4 and impairs the Y phosphorylation of STAT4 as shown in IFNa-treated HEK293T cells [11,12]. </font>

S_32 1 S_66 1 S_5 1 S_22 1

<font face="Georgia" size="2">Ca activates cam_ca [1]. </font>

<font face="Georgia" size="2">Calmodulin binding Ca<sup>2+</sup> leads to activation of Calmodulin [1,2]. </font>

S_56 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);">Cebpb activates the timescale dummy node 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_7 1 S_11 1

<font face="Georgia" size="2">Akt negatively regulates fkhr [1]. </font>

<font face="Georgia" size="2">Akt phosphorylates and thereby inhibits FKHR after IL-6 treatment as shown by human multiple myeloma MM.1S cells [1,2,3]. </font>

S_21 1 S_21 1

<font face="Georgia" size="2">Ras_gap is activated by gab1_mem_p and deactivated by shp2_a [1]. </font>

<font face="Georgia" size="2">Phosphorylated membrane bound Gab1 interacts with RasGAP [1,2]. </font>

<font face="Georgia" size="2">SHP2 dephosphorylates RasGAP and breaks apart Gab1 complexes as shown in EGF-treated Vero cells and MEFs [1,2]. </font>

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<font size="2" face="Georgia">IL6rc_p and jak1 are both required for activation of SHP2. SOCS3 is a negative regulator of SHP2 and is dominant over the positive regulators [1]. </font>

Binding of sirp1a to shp2 inhibits shp2 phosphorylation/activation.

ROS facilitates oxidative inhibition of SHP2.

<span style="font-family: Georgia; font-size: small;">SHP2 binds to phosphorylated Y759 of the gp130 subunit at its SH2 domain and becomes activated when JAK1 phosphorylates its tyrosine residues [1,2,3,4,5]. </span>

<font face="Georgia" size="2">SHP2 binds to phosphorylated Y759 of the gp130 subunit at its SH2 domain and becomes activated when JAK1 phosphorylates its tyrosine residues [1,2,3,4,5]. </font>

<font face="Georgia" size="2">SOCS3 competitively interacts with phosphorylated Y759 of the gp130 subunit blocking the SHP2 receptor as shown in HepG2 cells [1,6,7,8,9,10,11,12]. </font>

S_1 1 S_82 1 S_46 1 S_39 1 S_76 1

<font face="Georgia" size="2">Nfkb, dum_cebp_saa, and stat3_ta are all required for saa activation [1]. </font>

<font face="Georgia" size="2">NF-KB heterodimerises with STAT3 in response to IL-6 as shown in HepG2 cells [1,3,4]. </font>

<span style="font-family: Georgia; font-size: small;">NF-KB heterodimerises with STAT3 in response to IL-6 as shown in HepG2 cells [1,3,4]. </span>

<font face="Georgia" size="2">IL-6 activated C/EBPB and/or D causes SAA gene expression as shown in HepG2 cells [1,2]. </font>

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<font face="Georgia" size="2">IP3 activates Ca [1]. </font>

<font face="Georgia" size="2">IP3 causes Ca<sup>2+</sup> release as shown in human dermal foreskin fibroblasts [1,2,3]. </font>

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<font size="2" face="Georgia">CAMK24, ERK12, p70s6k, and stat3_ta are all positive regulators of pro_proliferative and each are individually sufficient to activate pro_proliferative. FKHR and CEBPB are both negative regulators of pro_proliferative. CEBPB is not dominant over any activators, while FKHR are dominant over all positive regulators [1]. </font>

<font face="Georgia" size="2">p70s6k induces cell cycle progression by inhibitory phosphorylation of the 4E-BP1 repressor and assembly of translation initiation complex as shown in IL-6 treated AF-10 MM cells [1,5]. </font>

<span style="font-family: Georgia; font-size: small;">CAM kinase II or the Ras/Raf/MEK/ERK/p90RSK cascade stop C/EBPB caused growth arrest as shown in TGFa treated HepG2 cells [1,2,3]. </span>

<font face="Georgia" size="2">CAM kinase II or the Ras/Raf/MEK/ERK/p90RSK cascade stop C/EBPB caused growth arrest as shown in TGFa treated HepG2 cells [1,2,3]. </font>

<font face="Georgia" size="2">C/EBPB homodimers are anti-proliferative, while C/EBPg neutralizes the growth-inhibitory effect as shown in HepG2 cells stopped in G1/S when over-expressing C/EBPB [1,8,9]</font>

<font face="Georgia" size="2">STAT3 promotes cell cycle progression and cell proliferation during liver growth. STAT3 plays a key role in human liver tumourigenesis by suppressing apoptosis [1,6,7]. </font>

<font face="Georgia" size="2">FKHR block G1/S phase transition by up-regulating p27KIP1 as shown in IL-6 treated human multiple myeloma cells [1,4]. </font>

S_79 1 S_6 1 S_13 1 S_33 1 S_79 1 S_33 1 S_6 1 S_11 1 S_13 1 S_52 1

<font face="Georgia" size="2">Shp2 and shp2_a can each independently activate tdum_shp2_stat3_py [1]. </font>

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

S_42 1 S_54 1

<font face="Georgia" size="2">PLCg activates IP3 [1]. </font>

<font face="Georgia" size="2">PLC gamma cleaves PIP2 creating IP3 and DAG [1,2]. </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);">Grb2_sos or il6rc_p can each activate grb2_sos [1]. </span>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Il6rc_p activates the timescale dummy node grb2_sos [1]. </span>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Grb2_sos activates the timescale dummy node grb2_sos [1]. </span>

S_37 1 S_1 1

\r\n \r\n \r\n \r\n <div class="page" title="Page 78">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><span style="font-size: 10.000000pt; font-family: 'Arial'; font-weight: 700">link to IL-1: </span><span style="font-size: 10.000000pt; font-family: 'ArialMT'">the transcriptional complex </span><span style="font-size: 10pt; font-family: ArialMT;">formation of cFOS:STAT3:HNF-1a (hepatocyte nuclear factor 1a) synergistically induces CRP gene expression in response to IL-(1+6)\r\nstimulation, whereas NF-</span><span style="font-size: 10pt; font-family: ArialMT;">?</span><span style="font-size: 10pt; font-family: ArialMT;">B seems to block\r\nthe early induction phase (as shown in\r\nHep3B cells</span><span style="font-size: 6pt; font-family: ArialMT; vertical-align: 5pt;">106b</span><span style="font-size: 10pt; font-family: ArialMT;">); contradictorily, IL-1-\r\ninduced NF-</span><span style="font-size: 10pt; font-family: ArialMT;">?</span><span style="font-size: 10pt; font-family: ArialMT;">B (p50:p65) was shown to act\r\nsynergistically with both C/EBP</span><span style="font-size: 10pt; font-family: ArialMT;">? </span><span style="font-size: 10pt; font-family: ArialMT;">and\r\nSTAT3 to mediate CRP gene expression in\r\nHep3B cells and therefore enhances the\r\neffects of IL-6 on CRP production</span><span style="font-size: 6pt; font-family: ArialMT; vertical-align: 5pt;">2b </span></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia" size="2">The complex of cFOS/STAT3/HNF-1a cause CRP gene expression as shown in Hep3B cells [1,2]. </font>

<font face="Georgia" size="2">NF-KB blocks the expression crp as shown in Hep3B cells [1,2,3]. </font>

<span style="font-family: Georgia; font-size: small;">The complex of cFOS/STAT3/HNF-1a cause CRP gene expression as shown in Hep3B cells [1,2]. </span>

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<font face="Georgia" size="2">Ras can activate PI3K. Alternately, Gab1_mem_p can activate PI3K when SHP2_a is inactive [1]. </font>

<font face="Georgia" size="2">GTP bound Ras interacts with PI3K and stimulates PI3K activation as shown in EGF and NGF treated (PC-12) rat phaeochromocytoma cells and over expression studies in COS cells [1,2]. </font>

<font face="Georgia" size="2">Phosphorylated membrane Gab1 interacts with PI3K at subunit p85 (shown in HepG2 cells) promotes PI3K activity as shown in IL-6 treated HEK293T cells [1,3,4,5]. </font>

<font face="Georgia" size="2">SHP2 dephosphorylates PI3K and down-regulates Gab1 interaction with PI3K as shown in EGF-treated NIH 3T3 and HEK293 cells [1,6]. </font>

S_47 1 S_83 1 S_42 1

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Gab1_kin or jak1 can each independently activate dum_gab1_kin_or_jak1_gab1_mem_p [1]. </span>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Jak1</span><span style="background-color: rgb(255, 255, 255); font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3;"> activates the timescale dummy node dum_gab1_kin_or_jak1_gab1_mem_p [1]. </span>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Gab1_kin activates the timescale dummy node dum_gab1_kin_or_jak1_gab1_mem_p [1]. </span>

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<span style="font-family: Georgia; font-size: small;">mTOR activates mtorc2 [1]. </span>

<span style="font-family: Georgia; font-size: small;">mTOR activates mtorc2 [1,2]. </span>

S_12 1

<font face="Georgia" size="2">IL6rc_p and Jak1 are both required to activate stat1_py. SHP2, SHP2_a, and cyt_ptpe are all inhibitors of stat1_py and are dominant over the activators [1]. </font>

<font face="Georgia" size="2">SHP2 acts as a phosphatase on STAT1 and dephosphorylate Y701 and S727 as shown in A431 cells upon EGF or IFN stimulation [1,9]. </font>

<font face="Georgia" size="2">JAK1 phosphorylates STAT1 at Y701 as shown in IL-6 treated HepG2 cells [1,6,11,8]. </font>

<font face="Georgia" size="2">STAT1 binds phosphorylated Y905 or phosphorylated Y915 on the IL-6 receptor complex on subunit gp130 on its SH2 domain [1,2,3]. STAT1 is only prevalent in the absence of STAT3 [1,4,5]. </font>

<font face="Georgia" size="2">cyt-PTPe inhibits the onset of STAT1-Y phosphorylation as shown in IL6-treated murine M1 myeloid cells [1,6,8,10]. </font>

<span style="font-family: Georgia; font-size: small;">SHP2 acts as a phosphatase on STAT1 and dephosphorylate Y701 and S727 as shown in A431 cells upon EGF or IFN stimulation [1,9]. </span>

S_1 1 S_82 1 S_44 1 S_42 1 S_54 1

<span style="font-family: Georgia; font-size: small;">mTOR activates mtorc1 [1]. </span>

<font face="Georgia" size="2">mTOR activates mtorc1 [1,2]. </font>

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<font face="Georgia" size="2">MK2 and camk24 are both inhibitors of gp130s [1]. </font>

<font face="Georgia" size="2">CAM2/4 was shown to phosphorylate gp130 at S782 in LIF-treated 3T3-L1 cells [1,5]. </font>

<font face="Georgia" size="2">MK2 phosphorylates gp130 at S782 causing degradation [1,2]. </font>

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<font face="Georgia" size="2">IL-6 is necessary to activate gp80m_a [1]. </font>

<font face="Georgia" size="2">IL-6 binds and forms the active IL-6/gp80membrane alpha-receptor complex [1,2]. </font>

S_4 1

<font face="Georgia" size="2">STAT3_ta activates anti_apoptotic. Bad, Casp9, and gsk3 are all negative regulators of anti_apoptotic and are dominant over the activators [1]. </font>

<font face="Georgia" size="2">STAT3 acts with PI3K/Akt pathways [1,5,6,7,8]. STAT3 regulates human liver tumourigenesis (hepatocellular carcinoma) by suppressing apoptosis during tumor growth [1,9,10]. </font>

<font face="Georgia" size="2">GSK3B negatively regulates transcription factors causing apoptosis [1,4]. </font>

<font face="Georgia" size="2">BAD inactivates the survival proteins Bcl-2 and Bcl-xL and promotes apoptosis [1,2]. </font>

<font face="Georgia" size="2">Casp9 activates apoptosis [1,3]. </font>

S_13 1 S_25 1 S_41 1 S_10 1

<font face="Georgia" size="2">Raf1 is activates MEK1 [1]. </font>

<font face="Georgia" size="2">Raf1 activates MEK1 by phosphorylation as shown in AF-10 cells [1,2]. </font>

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<span style="orphans: 3; widows: 3; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><span style="line-height: 18px;">Gp80m_a or gp80s_a can each independently activate dum_gp80_a_il6rc [1]. </span></font></span>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Gp80s_a activates the timescale dummy node dum_gp80_a_il6rc [1]. </span>

<span style="font-family: Georgia; font-size: small; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Gp80m_a activates the timescale dummy node dum_gp80_a_il6rc [1]. </span>

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<font face="Georgia" size="2">Shp2 or shp2_a can each individually activate tdum_shp2_stat1_py [1]. </font>

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

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\r\n \r\n \r\n <div class="page" title="Page 75">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p><font face="Georgia" size="2">ERK12, NFKB, p38, and stat3_ta are all positive regulators of SOCS3 and each are efficient to activate SOCS3 [1]. </font></p>\r\n </div>\r\n </div>\r\n </div>

<font face="Georgia" size="2">ERK12 inhibits STAT3 by increasing SOCS3 gene expression in HepG2 cells [1,8,9]. </font>

<font face="Georgia" size="2">p38 stabilizes and regulates transcription factors increasing SOCS3 mRNA as shown in IL-6 treated HepG2 cells [1,6,7]. </font>

<font face="Georgia" size="2">IL-1 stabilizes IL-6 induced SOCS3 mRNA using NF-KB as shown in IL-6 treated HepG2 [1,10]. </font>

<font face="Georgia" size="2">STAT3 activates SOCS genes in IL-6 treated HepG2 cells [1,2,3,4,5]. </font>

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<font face="Georgia" size="2">Gab1_mem can be activated by the joint activity of erk12 and pip3. Alternately, Gab1_mem can be activated by grb2_sos [1]. </font>

<font face="Georgia" size="2">Gab1 is phosphorylated at S551 by ERK1/2 relieving the inhibition at the pleckstrin homology domain as shown in IL-6 treated HEK293T cells [1,3,4,5]. Gab1 interacts with phosphorylated ERK2 possibly at Met-binding domain as shown in HGF-treated murine IMCD3 cells [1,6]. </font>

<font face="Georgia" size="2">PIP3 is used to phosphorylate Gab1 and activate it [1,3,4]. </font>

<font face="Georgia" size="2">Grb2 binds Gab1 at two SH3 domains as shown in HEK293T cells [1,2]. </font>

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<font face="Georgia" size="2">Akt, ERK12 and mtorc1 are all activators of p70s6k and are each sufficient for activation [1]. </font>

<span style="font-family: Georgia; font-size: small;">ERK1/2 contributes to p70S6K phosphorylation at T421/S424 as shown in IL-6 treated AF-10 MM cells [1,2]. </span>

<font face="Georgia" size="2">mTOR1 regulates p70S6K phosphorylation of T389 as shown in AF-10 MM cells [1,2], HepG2 cells [1,3], as well as S411 phosphorylation and T421/S424 phosphorylation as shown in AF-10 MM cells [1,2]. </font>

<font face="Georgia" size="2">Akt contributes to p70S6K phosphorylation at S411 or T389 as shown in IL-6 treated AF-10 MM cells [1,2]. </font>

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<font face="Georgia" size="2">Vav activates Rac1 [1]. </font>

<font face="Georgia" size="2">Vav associates with Rac1 and leads to GDP/GTP exchange on Rac1 and subsequent release of active GTP bound Rac1. Vav-Y phosphorylation is essential for Rac1 activation/GTP-Rac1 release as shown in HepG2 cells [1,2,3]. </font>

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<font face="Georgia" size="2">MEK6 activates p38 [1]. </font>

<font face="Georgia" size="2">IL-6 treatment induces phosphorylation of p38 at T180 and Y182 by MEK6 as shown in HepG2 cells [1,2] and human combined hepatocellular cholangio-carcinoma cells [1,3]. </font>

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<font face="Georgia" size="2">SH2, SH2_a, SOCS1 and SOCS3 are all negative regulators of JAK1 [1]. </font>

<font face="Georgia" size="2">SHP2 could be a phosphatase on JAK1 and exert inhibitory effects on JAK1 as shown in IL-6 treated rat hepatoma H-35 cells, and IL-5 treated COS-7 cells [1,6,7,8,9,10]. </font>

<span style="font-family: Georgia; font-size: small;">SHP2 could be a phosphatase on JAK1 and exert inhibitory effects on JAK1 as shown in IL-6 treated rat hepatoma H-35 cells, and IL-5 treated COS-7 cells [1,6,7,8,9,10]. </span>

<font size="2" face="Georgia">SOCS1 and SOCS3 inhibit gene induction in HepG2 cells [1,2]. SOCS1 interacts with JAK1 when its phosphorylated at Y in its SH2 domain leading to close proximity of its kinase inhibitory region domain with the substrate site of the kinase domain as shown in HEK293T cells over expressing SOCS1 and JAK1 [1,3,4,5]. </font>

<span style="font-family: Georgia; font-size: small;">SOCS1 and SOCS3 inhibit gene induction in HepG2 cells [1,2]. </span>

S_54 1 S_42 1 S_34 1 S_76 1 S_54 1 S_42 1 S_34 1 S_76 1

<font size="2" face="Georgia">Gab1_mem_p is activated by the joint activity of gab1_mem and dum_gab1_kin_or_jak1_gab1_mem_p [1]. </font>

<font face="Georgia" size="2">Membrane-bound Gab1 gets tyrosine phosphorylated after IL-6 stimulation as shown in HepG2 cells [1,2]. Phosphorylation is by JAK1 or another tyrosine protein kinase [1,2,3]. </font>

<span style="font-family: Georgia; font-size: small;">Membrane-bound Gab1 gets tyrosine phosphorylated after IL-6 stimulation as shown in HepG2 cells [1,2]. Phosphorylation is by JAK1 or another tyrosine protein kinase [1,2,3]. </span>

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<font face="Georgia" size="2">SOCS3 activates tdum_socs3_shp2 [1]. </font>

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

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<font face="Georgia" size="2">Stat3_ta is an activator of junb [1]. </font>

<font face="Georgia" size="2">IL-6 treatment causes gene expression via STAT3 as shown in HepG2 cells and murine hepatocytes [1,2,3]. </font>

S_13 1