Background Structural analysis of cellular interaction networks contributes to a deeper understanding of network-wide interdependencies, causal relationships, and basic functional capabilities. While the structural analysis of metabolic networks is a well-established field, similar methodologies have been scarcely developed and applied to signaling and regulatory networks. Results We propose formalisms and methods, relying on adapted and partially newly introduced approaches, which facilitate a structural analysis of signaling and regulatory networks with focus on functional aspects. We use two different formalisms to represent and analyze interaction networks: interaction graphs and (logical) interaction hypergraphs. We show that, in interaction graphs, the determination of feedback cycles and of all the signaling paths between any pair of species is equivalent to the computation of elementary modes known from metabolic networks. Knowledge on the set of signaling paths and feedback loops facilitates the computation of intervention strategies and the classification of compounds into activators, inhibitors, ambivalent factors, and non-affecting factors with respect to a certain species. In some cases, qualitative effects induced by perturbations can be unambiguously predicted from the network scheme. Interaction graphs however, are not able to capture AND relationships which do frequently occur in interaction networks. The consequent logical concatenation of all the arcs pointing into a species leads to Boolean networks. For a Boolean representation of cellular interaction networks we propose a formalism based on logical (or signed) interaction hypergraphs, which facilitates in particular a logical steady state analysis (LSSA). LSSA enables studies on the logical processing of signals and the identification of optimal intervention points (targets) in cellular networks. LSSA also reveals network regions whose parametrization and initial states are crucial for the dynamic behavior. We have implemented these methods in our software tool CellNetAnalyzer (successor of FluxAnalyzer) and illustrate their applicability using a logical model of T-Cell receptor signaling providing non-intuitive results regarding feedback loops, essential elements, and (logical) signal processing upon different stimuli. Conclusion The methods and formalisms we propose herein are another step towards the comprehensive functional analysis of cellular interaction networks. Their potential, shown on a realistic T-cell signaling model, makes them a promising tool. Helikar Tomas thelika@unmc.edu University of Nebraska - Lincoln 2015-02-09T12:00:08Z 2016-01-22T07:08:46Z

\r\n \r\n \r\n <div class="page" title="Page 5">\r\n <div class="section">\r\n <div class="layoutArea">\r\n <div class="column">\r\n <p style="font-family: Arial, Verdana;"><font face="Georgia" size="2"><u>Ligand of T cell receptor (peptide-MHC\r\ncomplex or antibody)</u></font></p><p style="font-family: Arial, Verdana;"><font face="Georgia" size="2">There are multiple ligands that bind to the various T cells. </font></p><p style="font-family: Arial, Verdana;"><font face="Georgia" size="2">Class I peptide-MHC complexes display to and are recognized by CD8+ T cells. Class II peptide MHC complexes are recognized by CD4+ T cells. </font><font face="Georgia" size="2">Class I MHC protein complexes are generated from three genes: HLA-A, HLA-B and HLC-C. The class I molecule consists of two non-covalently linked polypeptide chains: an alpha chain and a beta chain. </font><span style="background-color: rgb(255, 255, 255); font-family: Georgia; font-size: small; line-height: 15.989583969116211px;">Class II MHC protein complexes are a heterodimer held together by non-covalent interactions. These peptides are encoded by three genes.</span></p><p style="font-family: Arial, Verdana;"><font face="Georgia" size="2">Genes encoding MHC class I:</font></p><font face="Arial, Verdana" size="2"></font><ul><li><font face="Georgia"></font><dt class="desig" style="display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px !important;">Major histocompatibility complex, class I, A. Official Symbol: </dt><dd class="desig" style="margin: 0px; display: inline; padding: 0px;">HLA-A, NCBI Gene ID: 3105</dd></li><li><font face="Georgia"></font><dt class="desig" style="display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; background-color: rgb(255, 255, 255); margin-left: 0px !important;">Major histocompatibility complex, class I, B. Official Symbol: </dt><dd class="desig" style="margin: 0px; display: inline; padding: 0px; line-height: 16px; background-color: rgb(255, 255, 255);">HLA-B, NCBI Gene ID: 3106</dd></li><li><font face="Georgia"></font><dd class="desig" style="margin: 0px; display: inline; padding: 0px; line-height: 16px; background-color: rgb(255, 255, 255);"><span style="line-height: normal;">Major histocompatibility complex, class I, C. </span></dd><dt class="desig" style="display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; background-color: rgb(255, 255, 255); margin-left: 0px !important;">Official Symbol: </dt><dd class="desig" style="margin: 0px; display: inline; padding: 0px; line-height: 16px; background-color: rgb(255, 255, 255);">HLA-C, NCBI Gene ID: 3107</dd><span style="background-color: rgb(255, 255, 255); line-height: 16px;"> </span></li></ul></div><div class="column" style="font-family: Arial, Verdana;"><dd class="desig" style="margin: 0px; display: inline; padding: 0px; line-height: 16px; background-color: rgb(255, 255, 255);"><span style="font-family: Georgia; font-size: small; line-height: normal;">Genes encoding MHC class II:</span></dd></div><div class="column" style="font-family: Arial, Verdana;"><ul><li><span style="font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">Major histocompatibility complex, class II, DP, alpha 1. </span><dt class="desig" style="font-family: Georgia; font-size: small; display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; background-color: rgb(255, 255, 255); margin-left: 0px !important;">Official Symbol: </dt><dd class="desig" style="font-family: Georgia; font-size: small; margin: 0px; display: inline; padding: 0px; line-height: 16px; background-color: rgb(255, 255, 255);">HLA-DPA1. NCBI Gene ID:3113</dd></li><li><span style="font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">Major histocompatibility complex, class II, DP, beta 1. </span><dt class="desig" style="font-family: Georgia; font-size: small; display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; background-color: rgb(255, 255, 255); margin-left: 0px !important;">Official Symbol: </dt><dd class="desig" style="font-family: Georgia; font-size: small; margin: 0px; display: inline; padding: 0px; line-height: 16px; background-color: rgb(255, 255, 255);">HLA-DPB1. NCBI Gene ID:3115</dd></li><li><span style="font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">Major histocompatibility complex, class II, DQ, alpha 1. </span><dt class="desig" style="font-family: Georgia; font-size: small; display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; background-color: rgb(255, 255, 255); margin-left: 0px !important;">Official Symbol: </dt><dd class="desig" style="font-family: Georgia; font-size: small; margin: 0px; display: inline; padding: 0px; line-height: 16px; background-color: rgb(255, 255, 255);">HLA-DQA1. NCBI Gene ID:3117</dd></li><li><span style="font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">Major histocompatibility complex, class II, DQ, beta 1. </span><dt class="desig" style="font-family: Georgia; font-size: small; display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; background-color: rgb(255, 255, 255); margin-left: 0px !important;">Official Symbol: </dt><dd class="desig" style="font-family: Georgia; font-size: small; margin: 0px; display: inline; padding: 0px; line-height: 16px; background-color: rgb(255, 255, 255);">HLA-DQB1. NCBI Gene ID: 3119</dd></li><li><span style="font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">Major histocompatibility complex, class II, DR, alpha 1. </span><dt class="desig" style="font-family: Georgia; font-size: small; display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; background-color: rgb(255, 255, 255); margin-left: 0px !important;">Official Symbol: </dt><dd class="desig" style="font-family: Georgia; font-size: small; margin: 0px; display: inline; padding: 0px; line-height: 16px; background-color: rgb(255, 255, 255);">HLA-DRA. NCBI Gene ID: 3122</dd></li><li><span style="font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">Major histocompatibility complex, class II, DR, beta 1. </span><dt class="desig" style="font-family: Georgia; font-size: small; display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; background-color: rgb(255, 255, 255); margin-left: 0px !important;">Official Symbol: </dt><dd class="desig" style="font-family: Georgia; font-size: small; margin: 0px; display: inline; padding: 0px; line-height: 16px; background-color: rgb(255, 255, 255);">HLA-DRB1. NCBI Gene ID: 3123</dd></li><li><span style="font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">Major histocompatibility complex, class II, DR, beta 3. </span><dd class="desig" style="font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255); line-height: 16px; margin: 0px; display: inline; padding: 0px;"></dd><dt class="desig" style="display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px !important;">Official Symbol: </dt><dd class="desig" style="margin: 0px; display: inline; padding: 0px; line-height: 16px;">HLA-DRB3</dd> NCBI Gene ID: 3125</li><li><span style="font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">Major histocompatibility complex, class II, DR, beta 4. </span><dd class="desig" style="font-family: Georgia; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255); margin: 0px; display: inline; padding: 0px;"></dd><dt class="desig" style="font-family: Georgia; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255); display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px !important;">Official Symbol: </dt><dd class="desig" style="font-family: Georgia; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255); margin: 0px; display: inline; padding: 0px;">HLA-DRB4</dd><span style="font-family: Georgia; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"> NCBI Gene ID: 3126</span></li><li><span style="font-family: Georgia; font-size: small; background-color: rgb(255, 255, 255);">Major histocompatibility complex, class II, DR, beta 5. </span><dd class="desig" style="font-family: Georgia; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255); margin: 0px; display: inline; padding: 0px;"></dd><dt class="desig" style="font-family: Georgia; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255); display: inline; padding: 0px; margin-top: 0px; margin-right: 0px; margin-bottom: 0px; margin-left: 0px !important;">Official Symbol: </dt><dd class="desig" style="font-family: Georgia; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255); margin: 0px; display: inline; padding: 0px;">HLA-DRB5</dd><span style="font-family: Georgia; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"> NCBI Gene ID: 3127</span></li></ul></div><div class="column" style="font-family: Arial, Verdana;"><dd class="desig" style="margin: 0px; display: inline; padding: 0px; line-height: 16px; background-color: rgb(255, 255, 255);"></dd><dd class="desig" style="margin: 0px; display: inline; padding: 0px; line-height: 16px;"><font face="Georgia" size="2"><br/></font></dd></div><div class="column" style="font-family: Arial, Verdana;"><dd class="desig" style="margin: 0px; display: inline; padding: 0px; font-family: arial, helvetica, clean, sans-serif; font-size: 12px; line-height: 16px; background-color: rgb(255, 255, 255);"></dd><dd class="desig" style="margin: 0px; display: inline; padding: 0px; font-size: 12px; line-height: 16px;"><br/></dd></div>\r\n </div>\r\n </div>\r\n </div>

2015-11-15T20:53:55Z

<font face="Georgia" size="2" style="font-family: Arial, Verdana; font-size: 10pt; line-height: normal;"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">CD8a molecule [</span><em style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">Homo sapiens</em><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);"> (human)]</span></font><div style="font-family: Arial, Verdana; font-size: 10pt; line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P01732" style="text-decoration: none; background-color: rgb(255, 255, 255);">P01732</a></font></div><div style="font-family: Arial, Verdana; font-size: 10pt; line-height: normal;"><font face="Georgia" size="2"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/925" ref="ordinalpos=1&ncbi_uid=925&link_uid=925" style="line-height: 17.999801635742188px; white-space: nowrap; background-color: rgb(255, 255, 255);">CD8A</a></font></div><div style="font-family: Arial, Verdana; font-size: 10pt; line-height: normal;"><span style="line-height: 17.999801635742188px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">NCBI Gene ID: 925</font></span></div><div style="font-family: Arial, Verdana; font-size: 10pt; line-height: normal;"><br/></div><div style="font-family: Arial, Verdana; font-size: 10pt; line-height: normal;"><br/></div><div><font face="Georgia" size="2"><span style="line-height: 17.9998016357422px; background-color: rgb(255, 255, 255);">CD8+ Cytotoxic T Cells</span></font></div><div><font face="Georgia" size="2"><span style="line-height: 17.9998016357422px; background-color: rgb(255, 255, 255);"><br/></span></font></div>

2015-11-15T20:53:55Z

<div>Protein Tyrosine Phosphatase, receptor <span style="font-size: 10pt;">type, C</span></div><div><span style="font-size: 10pt;">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P08575" 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);">P08575</a></div><div><span style="font-size: 10pt;">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/5788" ref="ordinalpos=1&ncbi_uid=5788&link_uid=5788" style="color: rgb(100, 42, 143); font-family: arial, helvetica, clean, sans-serif; font-size: 13px; line-height: 17.9998016357422px; white-space: nowrap; background-color: rgb(213, 222, 227);">PTPRC</a></div><div><span style="font-size: 10pt;">Gene ID: </span><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);">5788</span></div><div><br/></div>

2015-11-15T20:53:55Z

Protein Associated with Glycosphingolipid enriched\r\nmicrodomains and  protein tyrosine kinase Csk (C-terminal Src-kinase) <div>PAG</div><div>UniProt ID: <a href="http://www.uniprot.org/uniprot/Q9NWQ8" 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);">Q9NWQ8</a></div><div>Gene Name: PAG1</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);">55824</span></div><div><br/></div><div>Csk</div><div>UniProt ID: <a href="http://www.uniprot.org/uniprot/P41240" 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);">P41240</a></div><div>Gene Name: CSK</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);">1445</span></div>

2015-11-15T20:53:55Z

<div><strong style="color: rgb(68, 68, 68); font-family: Verdana, Arial, sans-serif; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">AP-1 complex subunit gamma-1</strong></div>UniProt ID: <a href="http://www.uniprot.org/uniprot/O43747" style="text-decoration: none; color: rgb(64, 148, 180); border-bottom-width: 0px; cursor: pointer; font-family: Verdana, Arial, sans-serif; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">O43747</a><div>Gene Name: JUN</div><div>Gene ID: 3725</div>

2015-11-15T20:53:55Z

<span style="font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia">Protein kinase C theta type</font></span><div><font face="Georgia"><span style="font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);">UniProt ID: </span><span style="font-size: 16px; background-color: rgb(255, 255, 255);">Q04759</span></font></div><div><font face="Georgia"><span style="font-size: 16px; background-color: rgb(255, 255, 255);">Gene Name: PKC</span></font></div><div><font face="Georgia"><span style="font-size: 16px; background-color: rgb(255, 255, 255);">Gene ID: </span></font><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);">100152637</span></div>

2015-11-15T20:53:55Z

<div><font face="Georgia" size="2">Represents the inhibitor of nuclear factor kappa-B. </font></div><div><font face="Georgia" size="2"><span style="line-height: 16px; background-color: rgb(255, 255, 255);">Inhibitor of nuclear factor kappa-B kinase subunit beta </span></font></div><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);">O14920</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/4793" ref="ordinalpos=7&ncbi_uid=4793&link_uid=4793" style="line-height: 19.999780654907227px; white-space: nowrap; background-color: rgb(255, 255, 255);">NFKBIB</a></font></div><div><font face="Georgia" size="2">NCBI Gene ID: <span style="background-color: rgb(255, 255, 255); line-height: 17.999801635742188px;">4793</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 style="font-size: 10pt; font-family: Arial, Verdana;"><span style="font-size: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia"><br/></font></span></div><div style="font-size: 10pt; font-family: Arial, Verdana; font-weight: normal;"><strong style="font-family: sans-serif; font-size: 16px; background-color: rgb(255, 255, 255);"><br/></strong></div>

2015-11-15T20:53:55Z

binding of the peptide to TCR

2015-11-15T20:53:55Z

<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>

2015-11-15T20:53:55Z

<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);"><font face="Georgia" size="2">Cas-Br-M (murine) ecotropic retroviral transforming sequence<br/></font></p><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);"><font face="Georgia" size="2">Protein Product Name: <span style="line-height: 16px;">Kynurenine--oxoglutarate transaminase 1</span></font></p><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);"><font face="Georgia" size="2">UniProt ID: Q16773</font></p><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);"><font face="Georgia" size="2">Gene Name: CBL</font></p><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 style="font-family: Georgia; font-size: small;">Gene ID: </span><span style="font-family: Georgia; font-size: small; line-height: 18.8888893127441px;">867</span></p>

2015-11-15T20:53:55Z

<font style="line-height: normal; background-color: rgb(255, 255, 255);" face="Georgia" size="2"><span style="border: 0px; outline: 0px; font-style: inherit; font-variant: inherit; line-height: inherit; vertical-align: baseline; margin: 0px; padding: 0px;">Diacylglycerol </span></font><div><font face="Georgia" size="2">PubChem ID: <span style="line-height: 19px; background-color: rgb(255, 255, 255);">6026790</span></font></div><div><font face="Georgia" size="2"><span style="line-height: inherit; font-style: inherit; font-variant: inherit; border: 0px; outline: 0px; vertical-align: baseline; margin: 0px; padding: 0px;">Molecular Formula:</span><span style="background-color: rgb(255, 255, 255); line-height: inherit;"> </span><span style="background-color: rgb(255, 255, 255); line-height: inherit;">C</span><sub style="font-style: inherit; font-variant: inherit; border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px;">37</sub><span style="background-color: rgb(255, 255, 255); line-height: inherit;">H</span><sub style="font-style: inherit; font-variant: inherit; border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px;">70</sub><span style="background-color: rgb(255, 255, 255); line-height: inherit;">O</span><sub style="font-style: inherit; font-variant: inherit; border: 0px; outline: 0px; line-height: 0; margin: 0px; padding: 0px;">5</sub><span style="background-color: rgb(255, 255, 255); line-height: inherit;">   </span><span style="line-height: inherit; font-style: inherit; font-variant: inherit; border: 0px; outline: 0px; vertical-align: baseline; margin: 0px; padding: 0px;">Molecular Weight:</span><span style="background-color: rgb(255, 255, 255); line-height: inherit;"> </span><span style="background-color: rgb(255, 255, 255); line-height: inherit;">594.9487  </span></font></div>

2015-11-15T20:53:55Z

PLCg(bind)\r\nrefers to PLCgamma1 bound to LAT<div><div style="font-size: 13.3333330154419px;">UniProt ID: <a href="http://www.uniprot.org/uniprot/P19174" 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);">P19174</a></div><div style="font-size: 13.3333330154419px;">Gene Name: PLCG1</div><div style="font-size: 13.3333330154419px;">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);">5335</span></div></div>

2015-11-15T20:53:55Z

<font face="Arial, Verdana" style="font-style: normal; font-variant: normal; font-weight: normal;"><span style="font-size: 10pt;">RAF1 = v-raf-1 murine leukemia viral oncogene homolog 1 </span></font><div style="font-style: normal; font-variant: normal; font-weight: normal; font-family: Arial, Verdana; font-size: 10pt; line-height: normal;">UniProt ID: <a href="http://www.uniprot.org/uniprot/P04049" 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);">P04049</a></div><div style="font-style: normal; font-variant: normal; font-weight: normal; font-family: Arial, Verdana; font-size: 10pt; line-height: normal;">Gene Name: RAF1</div><div style="font-style: normal; font-variant: normal; font-weight: normal; font-family: Arial, Verdana; font-size: 10pt; line-height: normal;">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);">5894</span><br/><div><br/></div><div>BRAF = v-raf murine sarcoma viral oncogene homolog B1</div><div><div style="font-size: 13.3333330154419px;">UniProt ID: <a href="http://www.uniprot.org/uniprot/P15056" 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);">P15056</a></div><div style="font-size: 13.3333330154419px;">Gene Name: BRAF</div><div style="font-size: 13.3333330154419px;">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);">673</span></div></div><div><br/></div><div>ARAF = v-raf murine sarcoma 3611 viral oncogene homolog</div></div><div style="font-style: normal; font-variant: normal; font-weight: normal; font-family: Arial, Verdana; font-size: 10pt; line-height: normal;"><div style="font-size: 13.3333330154419px;">UniProt ID: <a href="http://www.uniprot.org/uniprot/P10398" 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);">P10398</a></div><div style="font-size: 13.3333330154419px;">Gene Name: ARAF</div><div style="font-size: 13.3333330154419px;">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);">369</span></div></div><div style="font-style: normal; font-variant: normal; font-weight: normal; font-family: Arial, Verdana; font-size: 13.3333330154419px; line-height: normal;"><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);"><br/></span></div><div>Pole hole Raf [fruit fly]</div><div>UniProt ID: <a href="http://www.uniprot.org/uniprot/P11346" 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);">P11346</a></div><div>Gene Name: phl</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);">31221</span></div>

2015-11-15T20:53:55Z

<div style="font-size: 10pt;">mitogen-activated protein kinase <span style="font-size: 10pt;">kinase 1</span></div><div style="font-size: 10pt;"><span style="font-size: 10pt;"><br/></span></div><div style="font-size: 10pt;">MAP2K5:</div><div style="font-size: 10pt;">UniProt Accession ID: Q13163</div><div style="font-size: 10pt;"><br/></div><div style="font-size: 10pt;">MAP2K6:</div><div style="font-size: 10pt;">UniProt Accession ID: P52564 </div><div style="font-size: 10pt;"><br/></div><div style="font-size: 10pt;">MAP2K3:</div><div style="font-size: 10pt;">UniProt Accession ID: P46734 </div><div style="font-size: 10pt;"><br/></div><div style="font-size: 10pt;">MAP2K1:</div><div style="font-size: 10pt;">UniProt Accession ID: Q02750</div><div style="font-size: 10pt;"><br/></div><div><font size="2">MAP2K2:</font></div><div><font size="2">UniProt Accession ID: P36507</font></div>

2015-11-15T20:53:55Z

ligand for the T Cell Receptor

2015-11-15T20:53:55Z

<div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.4000005722046px; background-color: rgb(255, 255, 255);"><span style="font-size: 10pt;">Also known as MKK4 or MAP2K4.</span></div><div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.4000005722046px; background-color: rgb(255, 255, 255);"><span style="font-size: 10pt;">Uniprot ID: </span><a href="http://www.uniprot.org/uniprot/P45985" style="outline: none; color: rgb(79, 79, 79); font-size: 10pt;">P45985</a></div>

2015-11-15T20:53:55Z

<p style="orphans: 3; widows: 3; margin: 0.4em 0px 0.5em; color: rgb(79, 79, 79); font-size: 12px; background-color: rgb(255, 255, 255);"><font face="Georgia">Calcineurin</font></p><p style="font-family: Arial, sans-serif; line-height: 18px; orphans: 3; widows: 3; margin: 0.4em 0px 0.5em; color: rgb(79, 79, 79); font-size: 12px; background-color: rgb(255, 255, 255);"><span id="parentSpecies:viewSpeciesDescription"><font face="Georgia" style="line-height: normal;">Heterodimer composed of one catalytic subunit and one regulatory subunit. </font></span></p><div style="font-family: Arial, sans-serif; line-height: 18px; font-size: 12px; color: rgb(79, 79, 79); background-color: rgb(255, 255, 255);"><font face="Georgia"><span style="line-height: normal;">There are three isoforms of the catalytic subunit:</span><font style="line-height: normal;"><br/></font></font><div style="line-height: normal;"><ul style="list-style-type: square; line-height: 1.5em; list-style-image: url(data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAAUAAAANCAMAAABW4lS6AAAAGXRFWHRTb2Z0d2FyZQBBZG9iZSBJbWFnZVJlYWR5ccllPAAAAAZQTFRFAFKM////QIUK9QAAAAJ0Uk5T/wDltzBKAAAAGklEQVR42mJgBAEGokgGBjBGBxBxsBqAAAMACHwALd5r8ygAAAAASUVORK5CYII=); margin: 0.3em 0px 0px 1.5em; padding: 0px;"><li style="margin-bottom: 0.1em;"><font face="Georgia"><span style="background-color: rgb(249, 249, 249); line-height: 16.890625px; text-align: center;"><span style="line-height: 16px; text-align: start; background-color: rgb(255, 255, 255);">Serine/threonine-protein phosphatase 2B catalytic subunit alpha isoform</span>, UniProt ID: </span>Q08209</font></li><li style="margin-bottom: 0.1em;"><font face="Georgia"><span style="line-height: 16.890625px; text-align: center; background-color: rgb(249, 249, 249);"><span style="line-height: 16px; text-align: start; background-color: rgb(255, 255, 255);">Serine/threonine-protein phosphatase 2B catalytic subunit beta isoform</span>, UnitProt ID:</span>P16298</font></li><li style="margin-bottom: 0.1em;"><font face="Georgia"><span style="line-height: 16px;">Serine/threonine-protein phosphatase 2B catalytic subunit gamma isoform, UniProt ID: </span>P48454</font></li></ul><div><font face="Georgia">There are two isoforms of the regulatory subunit:</font></div></div><div><ul style="list-style-type: square; line-height: 1.5em; list-style-image: url(data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAAUAAAANCAMAAABW4lS6AAAAGXRFWHRTb2Z0d2FyZQBBZG9iZSBJbWFnZVJlYWR5ccllPAAAAAZQTFRFAFKM////QIUK9QAAAAJ0Uk5T/wDltzBKAAAAGklEQVR42mJgBAEGokgGBjBGBxBxsBqAAAMACHwALd5r8ygAAAAASUVORK5CYII=); margin: 0.3em 0px 0px 1.5em; padding: 0px;"><li style="margin-bottom: 0.1em;"><font face="Georgia"><span style="line-height: 16px;">Calcineurin subunit B type 1, UniProt ID: </span>P63098</font></li><li style="margin-bottom: 0.1em;"><font face="Georgia"><span style="line-height: 16px;">Calcineurin subunit B type 2, UniProt ID: </span>Q96LZ3</font></li></ul></div></div>

2015-11-15T20:53:55Z

MAPK8 = mitogen-activated protein kinase 8<div>UniProt ID: <a href="http://www.uniprot.org/uniprot/P45983" 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(222, 239, 245);">P45983</a></div><div>Gene Name: MAPK8</div><div>Gene ID: 5599</div><div> </div><div>MAPK9 = mitogen-activated protein kinase 9 </div><div><div style="font-size: 13.3333330154419px;">UniProt ID: <a href="http://www.uniprot.org/uniprot/P45984" 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(222, 239, 245);">P45984</a></div><div style="font-size: 13.3333330154419px;">Gene Name: MAPK9</div><div style="font-size: 13.3333330154419px;">Gene ID: 5601</div></div><div style="font-size: 13.3333330154419px;"><br/></div><div style="font-size: 13.3333330154419px;">MAPK10 = mitogen-activated protein kinase 10 </div><div style="font-size: 13.3333330154419px;"><div style="font-size: 13.3333330154419px;">UniProt ID: <a href="http://www.uniprot.org/uniprot/P53779" 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(222, 239, 245);">P53779</a></div><div style="font-size: 13.3333330154419px;">Gene Name: MAPK10 </div><div style="font-size: 13.3333330154419px;">Gene ID:v5602</div></div>

2015-11-15T20:53:55Z

<font face="Arial, Verdana" size="2" style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;">FYN oncogene related to SRC, FGR, YES</font><div style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><font face="Arial, Verdana" size="2"><br/></font></div><div style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><span style="font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);">Tyrosine-protein kinase Fyn</span></div><div style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><span style="font-family: sans-serif; font-size: small; line-height: 16px; background-color: rgb(255, 255, 255);">UniProt Accession ID: P06241</span><span style="font-family: sans-serif; font-size: 16px; background-color: rgb(255, 255, 255);"> </span></div><div style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><span style="font-family: sans-serif; font-size: 16px; background-color: rgb(255, 255, 255);"><br/></span></div><div style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><span style="font-family: sans-serif; font-size: 16px; background-color: rgb(255, 255, 255);">For more info:</span></div><div><span style="background-color: rgb(255, 255, 255);"><font face="sans-serif">http://www.ncbi.nlm.nih.gov/mesh/68051076</font></span></div>

2015-11-15T20:53:55Z

FBJ murine osteosarcoma viral oncogene homolog <br/><div>UniProt ID: P01100</div><div>Gene Name: FOS</div><div>Gene ID: 2353</div>

2015-11-15T20:53:55Z

Scaffolding protein <font color="#444444" face="Verdana, Arial, sans-serif"><span style="font-size: 13.0571994781494px; line-height: 20.081974029541px; background-color: rgb(255, 255, 255);">GRB2-related adapter protein 2</span></font> (GADS)<div style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><span style="font-size: 10pt;">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/O75791" 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);">O75791</a><div>Gene Name: Grap2</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);">17444</span></div></div>

2015-11-15T20:53:55Z

<span style="font-family: Arial, Verdana; font-size: small; font-style: normal; font-variant: normal; font-weight: normal; line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia">Transcription factor AP-1, </font></span><font face="Arial, Verdana"><span style="font-size: 10pt;">jun proto-oncogene</span></font><div>UniProt ID: P05412</div><div>Gene Name: JUN</div><div>Gene ID: 3725</div>

2015-11-15T20:53:55Z

<table style="width: 723pt; border-collapse: collapse;" border="0" cellSpacing="0" cellPadding="0" width="964">\r\n <colgroup><col style="width: 723pt; mso-width-source: userset; mso-width-alt: 30848;" width="964">\r\n <tbody><tr style="height: 15pt;" height="20">\r\n\r\n <td style="border: 0px black; width: 723pt; height: 15pt; background-color: transparent;" class="xl65" height="20" width="964"><font size="3" face="Calibri">nuclear\r\n factor of kappa light polypeptide gene enhancer in B-cells 1 & RELA</font></td>\r\n\r\n </tr>\r\n</tbody></table><p>UniProt ID: <a href="http://www.uniprot.org/uniprot/P19838">P19838</a></p><p>Gene Name: RELA</p><p>Gene ID: 5970</p>

2015-11-15T20:53:55Z

<span class="RECOMMENDED" style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><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;">Lymphocyte cytosolic protein 2</span></font></span><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/><acronym class="names FULL" style="border: none; cursor: pointer; padding-left: 1em;"></acronym><span class="FULL_NAME">SH2 domain-containing leukocyte protein of 76 kDa</span><br/><acronym class="names FULL" style="border: none; cursor: pointer; padding-left: 1em;"></acronym><span class="FULL_NAME">SLP-76 tyrosine phosphoprotein</span><br/><acronym class="names SHORT" title="Abbreviation of the full name or an acronym." style="border: none; cursor: pointer; padding-left: 2em;">Short name=</acronym><span class="SHORT_NAME">SLP76</span></font></div><div class="alternatives" style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><span class="SHORT_NAME">UniProt ID: </span><span style="line-height: normal;">Q13094</span></font></div>

2015-11-15T20:53:55Z

<div><span style="font-size: 10pt;">lymphocyte specific Src-family protein tyrosine kinase p56lck</span></div><div><span style="font-size: 10pt;">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/P06239" 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);">P06239</a></div><div><span style="font-size: 10pt;">Gene Name: LCK</span></div><div><span style="font-size: 10pt;">Gene ID: </span><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);">3932</span></div>

2015-11-15T20:53:55Z

Transcription factor cAMP response elements (CRE)<div style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><br/></div>

2015-11-15T20:53:55Z

<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"><font face="Georgia" size="2">Complex between Grb2 and SOS</font></span></p><div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.4000005722046px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Growth factor receptor-bound protein 2</font><div><font face="Georgia"><font size="2">UniProt Accession ID: </font><font size="2">Q60631</font></font></div><div><font face="Georgia" size="2">Gene Name: <a href="http://www.ncbi.nlm.nih.gov/gene/2885" ref="ordinalpos=1&ncbi_uid=2885&link_uid=2885" style="outline: none; color: rgb(79, 79, 79); line-height: 18.8888893127441px; white-space: nowrap;"><span class="highlight">GRB2</span></a></font></div><div><font size="2" face="Georgia">Gene ID: 2885</font></div></div><div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.4000005722046px; background-color: rgb(255, 255, 255);"><span style="line-height: 19.9997806549072px;"><font face="Georgia" size="2">Son of sevenless homolog 1 </font></span></div><div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.4000005722046px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><span style="line-height: 19.9997806549072px;">UniProt ID: </span><a href="http://www.uniprot.org/uniprot/Q07889" style="outline: none; color: rgb(79, 79, 79); text-decoration: none;">Q07889</a></font></div><div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.4000005722046px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><span style="line-height: 19.9997806549072px;">Gene Name: </span><a href="http://www.ncbi.nlm.nih.gov/gene/6654" ref="ordinalpos=5&ncbi_uid=6654&link_uid=6654" style="outline: none; color: rgb(79, 79, 79); line-height: 19.9997806549072px; white-space: nowrap;">SOS1</a></font></div><div style="font-size: 12px; color: rgb(79, 79, 79); font-family: Arial, sans-serif; line-height: 14.4000005722046px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2"><span style="line-height: 19.9997806549072px;">Gene ID: </span><span style="line-height: 17.9998016357422px;">6654</span></font></div>

2015-11-15T20:53:55Z

<div><font face="Georgia" size="2">cAMP responsive element binding protein 1</font></div><div><span style="line-height: 16px; background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Cyclic AMP-responsive element-binding protein 1</font></span></div><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);">P16220</span></font></div><div><span style="background-color: rgb(255, 255, 255);"><font face="Georgia" size="2">Gene Name: CREB1</font></span></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: 18.88888931274414px;">1385</span></font></div>

2015-11-15T20:53:55Z

Active form of PLCg1<div>UniProt ID: <a href="http://www.uniprot.org/uniprot/P19174" 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);">P19174</a></div><div>Gene Name: PLCG1</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);">5335</span></div>

2015-11-15T20:53:55Z

<table style="width: 723pt; border-collapse: collapse;" border="0" cellSpacing="0" cellPadding="0" width="964">\r\n <colgroup><col style="width: 723pt; mso-width-source: userset; mso-width-alt: 30848;" width="964">\r\n <tbody><tr style="height: 15pt;" height="20">\r\n\r\n <td style="border: 0px black; width: 723pt; height: 15pt; background-color: transparent;" class="xl65" height="20" width="964"><font size="3"><font face="Calibri">zeta-chain\r\n (TCR) associated protein kinase 70kDa<span style="mso-spacerun: yes;"> </span></font></font></td>\r\n\r\n </tr>\r\n</tbody></table><p> </p><p>UniProt ID: <a href="http://www.uniprot.org/uniprot/P43403">P43403</a></p><p>Gene Name: ZAP70</p><p>Gene ID: 7535</p>

2015-11-15T20:53:55Z 2015-11-15T20:53:55Z

RPS6KA1 = ribosomal protein S6 kinase, 90kDa, polypeptide 1 <div>UniProt ID: <a href="http://www.uniprot.org/uniprot/Q15418" 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(222, 239, 245);">Q15418</a></div><div>Gene Name: RPS6KA1</div><div>Gene ID: 6195</div><div><br/><div>RPS6KA2 = ribosomal protein S6 kinase, 90kDa, polypeptide 2 </div><div><div style="font-size: 13.3333330154419px;">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q15349" 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);">Q15349</a></div><div style="font-size: 13.3333330154419px;">Gene Name: <span style="font-size: 13.3333330154419px;">RPS6KA2</span></div><div style="font-size: 13.3333330154419px;">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);">6196</span></div></div><div style="font-size: 13.3333330154419px;"><br/></div><div>RPS6KA3 = ribosomal protein S6 kinase, 90kDa, polypeptide 3 </div><div><div style="font-size: 13.3333330154419px;">UniProt ID: <a href="http://www.uniprot.org/uniprot/P51812" 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(222, 239, 245);">P51812</a></div><div style="font-size: 13.3333330154419px;">Gene Name: <span style="font-size: 13.3333330154419px;">RPS6KA3</span></div><div style="font-size: 13.3333330154419px;">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);">6197</span></div></div><div style="font-size: 13.3333330154419px;"><br/></div><div>RPS6KA6 = ribosomal protein S6 kinase, 90kDa, polypeptide 6 </div></div><div><div style="font-size: 13.3333330154419px;">UniProt ID: <a href="http://www.uniprot.org/uniprot/Q9UK32" 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);">Q9UK32</a></div><div style="font-size: 13.3333330154419px;">Gene Name: <span style="font-size: 13.3333330154419px;">RPS6KA6</span></div><div style="font-size: 13.3333330154419px;">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);">27330</span></div></div>

2015-11-15T20:53:55Z

<span style="font: 10pt/normal Arial, Verdana;">Raspberry</span> Ras-like protein 2<font face="Arial, Verdana"><span style="font-size: 10pt;"> (RAS)</span></font><div style="font: 10pt/normal Arial, Verdana;">UniProt ID: <a style="color: rgb(64, 148, 180); line-height: 20.08px; font-family: Verdana, Arial, sans-serif; font-size: 13.05px; text-decoration: none; border-bottom-width: 0px; cursor: pointer; background-color: rgb(255, 255, 255);" href="http://www.uniprot.org/uniprot/P04388">P04388</a></div><div style="font: 10pt/normal Arial, Verdana;">Gene Name: ras</div><div style="font: 10pt/normal Arial, Verdana;">Gene ID: <span style="color: rgb(87, 87, 87); line-height: 16.19px; font-family: arial, helvetica, clean, sans-serif; font-size: 11.69px; background-color: rgb(213, 222, 227);">43873</span></div><div style="font: 10pt/normal Arial, Verdana;"><span style="color: rgb(87, 87, 87); line-height: 16.19px; font-family: arial, helvetica, clean, sans-serif; font-size: 11.69px; background-color: rgb(213, 222, 227);"></span> </div><div style="font: 10pt/normal Arial, Verdana;"><span style="color: rgb(87, 87, 87); line-height: 16.19px; font-family: arial, helvetica, clean, sans-serif; font-size: 11.69px; background-color: rgb(213, 222, 227);"></span> </div><div style="font: 10pt/normal Arial, Verdana;"><span style="color: rgb(87, 87, 87); line-height: 16.19px; font-family: arial, helvetica, clean, sans-serif; font-size: 11.69px; background-color: rgb(213, 222, 227);"><table style="width: 723pt; border-collapse: collapse;" border="0" cellSpacing="0" cellPadding="0" width="964">\r\n <colgroup><col style="width: 723pt; mso-width-source: userset; mso-width-alt: 30848;" width="964">\r\n <tbody><tr style="height: 15pt;" height="20">\r\n\r\n <td style="border: 0px black; width: 723pt; height: 15pt; background-color: transparent;" class="xl65" height="20" width="964"><p><font color="#000000" size="3" face="Calibri"><font color="#575757" face="Arial">In [1]:</font></font></p><p><font color="#000000" size="3" face="Calibri">rat\r\n sarcoma viral oncogene homolog</font></p><p><font color="#000000" size="3" face="Calibri">Protein family</font><font color="#000000" size="3" face="Calibri"> </font></p></td>\r\n\r\n </tr>\r\n</tbody></table></span></div>

2015-11-15T20:53:55Z

Linker for Activation\r\nof T-cells<div>UniProt ID: <a href="http://www.uniprot.org/uniprot/O43561" 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);">O43561</a><br/>Gene Name: LAT</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);">27040</span></div>

2015-11-15T20:53:55Z

<table border="0" cellpadding="0" cellspacing="0" width="964" style="border-collapse:\r\n collapse;width:723pt"><tbody><tr height="20" style="height:15.0pt">\r\n <td height="20" class="xl64" width="964" style="height:15.0pt;width:723pt">Inositol\r\n 1,4,5-trisphosphate<br>Gene Name: IP3<br>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);">24019742</span></td></tr></tbody></table>

2015-11-15T20:53:55Z

From the paper [1]:<div><br/><div>MAPK1 = mitogen-activated protein kinase 1</div><div>UniProt ID: <a href="http://www.uniprot.org/uniprot/P28482" 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(222, 239, 245);">P28482</a></div><div>Gene Name: MAPK1</div><div>Gene ID: 5594</div><div><br/></div><div>MAPK3 = mitogen-activated protein kinase 3</div><div><div style="font-size: 13.3333330154419px;">UniProt ID: <a href="http://www.uniprot.org/uniprot/P27361" 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);">P27361</a></div><div style="font-size: 13.3333330154419px;">Gene Name: MAPK3</div><div style="font-size: 13.3333330154419px;">Gene ID: 5595</div></div></div>

2015-11-15T20:53:55Z

<table style="width: 723pt; border-collapse: collapse;" border="0" cellSpacing="0" cellPadding="0" width="964">\r\n <colgroup><col style="width: 723pt; mso-width-source: userset; mso-width-alt: 30848;" width="964">\r\n <tbody><tr style="height: 15pt;" height="20">\r\n\r\n <td style="border: 0px black; width: 723pt; height: 15pt; background-color: transparent;" class="xl65" height="20" width="964"><p><font size="3" face="Calibri">nuclear\r\n factor of activated T-cells, cytoplasmic, calcineurin-dependent</font></p><p><font size="3" face="Calibri">(NFAT homolog)</font></p><p><font size="3" face="Calibri">Gene Name: NFAT</font></p><p><font size="3" face="Calibri">Gene ID: 32321</font></p><p> </p></td>\r\n\r\n </tr>\r\n</tbody></table>

2015-11-15T20:53:55Z

<div style="font-family: Arial, Verdana; font-size: 10pt; font-style: normal; font-variant: normal; font-weight: normal; line-height: normal;"><table border="0" cellpadding="0" cellspacing="0" width="964" style="border-collapse:\r\n collapse;width:723pt"><tbody><tr height="20" style="height:15.0pt">\r\n <td height="20" class="xl65" width="964" style="height:15.0pt;width:723pt">IL2-inducible\r\n T-cell kinase </td></tr></tbody></table></div><span style="font-family: Arial, Verdana; font-size: 10pt;">Tyrosine-protein kinase ITK/TSK</span><div>UniProt ID: Q08881</div><div>Gene Name: ITK</div><div>Gene ID: 3702</div>

2015-11-15T20:53:55Z

PAGCsk is positively regulated by Fyn or TCRbind [1, 2].

TCRbind activates PAGCsk [1]

"After a few minutes, PAG is rephosphorylated,\r\nprobably by the Src-kinase Fyn, and subsequently Csk is\r\nre-recruited to PAG" [1, 2]

S_18 1

<span style="font-size: 13.3333330154419px;">Fos in conjunction with Jun activates the transcription factor AP1 [1].</span>

Fos in conjunction with Jun activates the transcription factor AP1 [1].

S_19 1 S_22 1

DAG positively regulates PKCth [1].

The second messenger DAG activates PKC? [1].

S_9 1

<span style="font-size: 13.3333330154419px;">IKKbeta inhibits Ikb [1].</span>

IKKbeta inhibits Ikb [1].

S_21 1

<span style="font-size: 13.3333330154419px;">TCRlig positively regulates TCRbind [1]. </span><span style="font-size: 13.3333330154419px;">cCbl negatively regulates TCRbind [1].</span>

TCRlig positively regulates TCRbind [1].

cCbl negatively regulates TCRbind [1].

S_8 1 S_7 1

IP3 positively regulates Ca [1].

IP3 mediates calcium flux [1].

S_36 1

ZAP70 positively regulates cCbl [1].

cCbl binds to ZAP70 [1]

S_30 1

PLCg_act indirectly activates DAG [1, 2, 3].

Activated PLCgamma1 generates the second messenger molecules\r\ndiacyloglycerol (DAG) [1, 2, 3].

S_29 1

LAT activates PLCg_bind [1].

phosphorylated LAT binds to PLCg_bind [1].

S_34 1

Ras activates Raf [1].

Ras activates the Raf/MEK/ERK/MAPK cascade [1].

S_33 1

Raf activates Mek [1].

Raf activating Mek is part of the Raf/Mek/ERK/MAPK cascade [1]

S_11 1

<span style="font-size: 13.3333330154419px;">Fyn activates TCRphos [1].</span>

Fyn activates TCRphos [1].

S_18 1

PKCth positively regulates SEK [1].

<span style="font-size: 13.3333330154419px;">PKCth positively regulates SEK [1].</span>

S_3 1

Ca activates calcin [1].

Calcium (together with calmodulin)\r\nactivates the serine phosphatase calcineurin [1]

S_6 1

SEK activates JNK [1].

<span style="font-size: 13.3333330154419px;">SEK activates JNK [1].</span>

S_14 1

LCK and CD45 activates FYN [1]. TCRbind and CD45 activate FYN [1, 2].

Fyn can probably also be activated in a Lck-independent,\r\nTCR-dependent manner [1, 2]

CD45 acts on its substrate FYN [1].

Activated Lck can phosphorylate another member of the\r\nSrc-protein kinases, p59fyn. [1]

S_40 1 S_25 1 S_5 1 S_40 1

ERK activates fos [1].

<span style="font-size: 13.3333330154419px;">ERK activates fos [1].</span>

S_37 1

LAT positively regulates gads [1].

<span style="font-size: 13.3333330154419px;">LAT positively regulates gads [1].</span>

S_34 1

PKCth positively regulates IKKbeta [1].

<span style="font-size: 13.3333330154419px;">PKCth positively regulates IKKbeta [1].</span>

S_3 1

JNK activates jun [1].

<span style="font-size: 13.3333330154419px;">JNK activates jun [1].</span>

S_17 1

<span style="font-size: 13.3333330154419px;">IkB inhibits NFKB [1].</span>

IkB inhibits NFKB [1].

S_4 1

Gads activates SLP76 [1].

Gads binds to the adapter protein\r\nSLP76 [1].

S_20 1

CD45 positively regulates LCK [1]. <span style="font-size: 13.3333330154419px;">CD8 positively regulates LCK [1]. </span><span style="font-size: 13.3333330154419px;">PAGCsk negatively regulates LCK [1].</span>

<span style="font-size: 13.3333330154419px;">CD8 positively regulates LCK [1]</span>

"Transmembrane adaptor protein PAG\r\n(Protein Associated with Glycosphingolipid enriched\r\nmicrodomains) consequently inhibits membranebound\r\nLck" [1]

"The release of\r\nCsk from PAG, together with the activity of the membrane\r\nassociated tyrosine phosphatase CD45 (which dephosphorylates\r\nLck" [1]

S_40 1 S_15 1 S_1 1

CREB activates CRE [1].

<span style="font-size: 13.3333330154419px;">CREB activates CRE [1].</span>

S_28 1

<span style="font-size: 13.3333330154419px;">LAT binds to Grb2Sos [1].</span>

LAT binds to Grb2Sos [1].

S_34 1

Rsk positively regulates CREB [1].

<span style="font-size: 13.3333330154419px;">Rsk positively regulates CREB [1].</span>

S_32 1

ZAP70 in conjunction with SLP76 and PLCg_bind and Itk activate PLCg_act [1]. <span style="font-size: 13.3333330154419px;">ZAP70 in conjunction with SLP76 and PLCg_bind and Rlk activate PLCg_act [1].</span>

<span style="font-size: 13.3333330154419px;">Rlk activates PlCg_act [1].</span>

Itk activates PlCg_act [1].

<span style="font-size: 13.3333330154419px;">PLCg_bind activates PlCg_act [1].</span>

<span style="font-size: 13.3333330154419px;">ZAP70 activates PlCg_act [1].</span>

<span style="font-size: 13.3333330154419px;">SLP76 activates PlCg_act [1].</span>

S_30 1 S_31 1 S_10 1 S_24 1 S_39 1 S_10 1 S_30 1 S_24 1

Lck positively regulates ZAP70 [1]. TCRphos positively regulates ZAP70 [1]. cCbl inhibits ZAP70 [1].

TCRphos positively regulates ZAP70 [1].

One important target of cCbl is ZAP70 [1].

Lck activates ZAP70 [1].

S_13 1 S_25 1 S_7 1

S_25 1

ERK positively regulates RSK [1].

<span style="font-size: 13.3333330154419px;">ERK positively regulates RSK [1].</span>

S_37 1

Grb2Sos positively regulates Ras [1]. RasGRP1 positively regulates Ras [1].

 RasGRP1 and Sos (the latter if it is close to the membrane,\r\nthat is, if it is bound to LAT by means of Grb2), can\r\nactivate Ras [1]

RasGRP1 and Sos (the latter if it is close to the membrane, that is, if it is bound to LAT by means of Grb2), can activate Ras [1]

S_35 1 S_27 1

ZAP70 activates lat [1].

Active ZAP70 can phosphorylate LAT (Linker for Activation\r\nof T-cells), a second transmembrane adapter protein. [1]

S_30 1

DAG in conjunction with PKCth activates RasGRP1 [1].

The second messenger DAG activates PKCtheta and\r\n(together with PKCtheta) activates the nucleotide\r\nexchange factor RasGRP1 [1]

The second messenger DAG activates PKCtheta and\r\n(together with PKCtheta) activates the nucleotide\r\nexchange factor RasGRP1 [1].

S_3 1 S_9 1

PLCg_act positively regulates IP3 [1, 2, 3].

 Activated PLCgamma1 generates the second messenger molecule inositol trisphosphate\r\n(IP3) [1, 2, 3].

S_29 1

MEK positively regulates ERK [1].

ERK is activated by the Ras/Raf/MEK cascade [1].

S_12 1

Calcin positively regulates NFAT [1].

Calcineurin dephosphorylates the cytosolic form of the transcription\r\nfactor NFAT (Nuclear Factor of Activated Tcells).\r\nThe calcineurin-mediated removal of phosphate\r\ngroups allows NFAT to translocate to the nucleus and to\r\nregulate gene expression. [1]

S_16 1

SLP76 activates Itk [1]. ZAP70 positively regulates ITK [1].

<span style="font-size: 13.3333330154419px;">Adapter protein SLP76 can bind to the Tec-family tyrosine kinase Itk. Binding to SLP76 and additional phosphorylation by ZAP70 activates Itk [1]</span>

Adapter protein\r\nSLP76 can bind to the Tec-family tyrosine kinase Itk. Binding to\r\nSLP76 and additional phosphorylation by ZAP70 activates\r\nItk [1]

S_30 1 S_24 1