JAK3 couples to IL2R and is activated [1-3].<br/>

ERKs phosphorylate TCF/Elk-1 and thereby induce c-Fos synthesis, leading to AP-1 transcription [1,2,4].<br/>

JNK-mediated phosphorylation of ATF2 and AP1(c-Jun) bound to the AP1(c-jun) promoter stimulates their transcriptional activities leading to AP1(c-jun) induction. The newly synthesized c-Fos and AP1(c-Jun) proteins combine to form stable AP-1 heterodimers. A further increase in\r\n AP-1 activity is brought about by the JNKs, which phosphorylate AP1(c-Jun) [1,2,4].<br/>

STAT4 binds AP-1 to promote higher levels of AP-1 binding to the IFNG promoter. [1,2,4]

Beta integrins bind soluble and insoluble ligands from the extracellular matrix [1,3,4].<br/>

Stimulation of the CD3–T-cell receptor(TCR) complex results in rapid increases in ß1&nbsp;integrin-mediatedadhesion [2,5,6].<br/>

TBET induces expression of HLX and interact with it to promote IFNG signaling. [1-3]

IRF1 inhibits Interleukin 4 production by binding to three distinct promoter sites for Interleukin 4.&nbsp;<span style="font-size: 10pt;">[1][6]</span>

Proliferation is denoted as a time point in the model when the cell has the correct parameters to proliferate. [1] It work with transcription factors GATA3 and NFAT to promote the expansion of a differentiated T cell, in this case, a TH2 cell.&nbsp;<span style="font-size: 10pt;">[1][2][5]</span>

RUNX3 cooperates with transcription factor TBET to bind to the Interferon Gamma promoter and the Interleukin 4 silencer.&nbsp;<span style="font-size: 10pt;">[1][2][5]</span>

TBET cooperates with transcription factor RUNX3 to bind the Interferon Gamma promoter and the Interleukin 4 silencer to inhibit Interleukin 4 production.&nbsp;<span style="font-size: 10pt;">[1][2][5]</span>

<div>The transcription factor NFAT works with transcription factor GATA3 and proliferation. NFAT and proliferation are needed for expansion of differentiated CD4 T helper cells.&nbsp;<span style="font-size: 10pt;">[1][2][4]</span></div>

<div>IRF4 is responsible for the production of Interleukin 2,4, and IFNG. It transactivates the promoter for Interleukin 4.&nbsp;<span style="font-size: 10pt;">[7][8]</span></div>

<div>GATA3 induces expression of Interleukin 4 through epigenetic modification. [1][3] GATA3 requires transcription factor NFAT as well as proliferation to induce Interleukin 4. [1][2]&nbsp;</div>

<div>FOXP3 blocks the expression of transcription factor, NFAT, thus inhibiting Interleukin 4 expression.&nbsp;<span style="font-size: 10pt;">[1][4]</span></div>

The proline-rich region of WAVE-2 binds to C-terminal end of IRSp53 [1-3].<br/>

<font face="Arial" size="2"><font size="2">A</font>ctivated Rac binds to the Rac-binding domain (RCB) in the N-terminus of IRSp53. The C-terminal SH3 domain of</font><font face="Arial" size="2">IRSp53 binds to WAVE to form a trimolecular complex [1-3].</font><br/>

SMAD3 cooperates with NFAT to activate IL2RA. [1-3]

STAT5 cooperates with NFAT to activate IL2RA. [1-3]

NFKB can cooperate with NFAT to promote IL2RA activity. [1-3]

NFAT is required and can cooperate with FOXP3, NFKB, SMAD3, or STAT5 to activate IL2RA. [1-3]

FOXP3 activates IL2RA to promote a higher level of interleukin 2 signaling. [1-3]

Once localized to the membrane, via ZAP-70 and Galpha i, DAG binds to the DAG binding domain of RasGRP, thereby activating it [1-4].<br/>

Profilin catalyzes the exchange of ADP for ATP on g-actin, refilling the pool of ATP-actin monomers bound to profilin [1-4].

STAT6 down-regulates the gene for IL12RB2. [1-3]

IL12_e binds to IL12RB2 to start the activation of the Interleukin 12 pathway. [1-3]

IL2RA is a subunit of IL2R and is required for IL2 signaling. IL2RA is needed for the high affinity response. [1-3]

Internal source of interleukin 2 that binds IL2R. [1-3]

IL2RB is a subunit of IL2R and is required for IL2 signaling. [1-3]

External source of interleukin 2 that binds IL2R. [1-3]

CGC is the common gamma chain that is a subunit of the IL2R. Its activity is required for IL2R signaling. [1-3]

STAT6 binds to the promoter of SOCS1 and thus activating it. [1-4]

STAT3 activates SOCS1 [1-5]

Mutual binding to Nck and Vav-1 brings together WASP with Cdc42-GTP [1,2,5].

WASP contains a proline-enriched segment through which it interacts with Nck [1,2,5].<br/>

WASP contains a cdc42/Rac interactive binding (CRIB) motif, which mediates WASP binding to the activated form of the cdc42 guanosine\r\n triphosphatase [1,3,4].<br/>

After autophosphorylation on Y397 of FAK, Src binds via the SH2 domain and phosphorylates FAK on Tyrosine residues 576 and 577 [1-4].<br/>

FAK (Y397) for the Src SH2 domain, allowing Src to phosphorylate FAK [1-4].<br/>

EPAC is a GEF directly activated by cAMP [1-3].<br/>

STAT1 activates IRF1. [1-3]

IRAK1 transloactes TRAF6 and activates it [1-3].<br/>

PAK decreases MLC phosphorylation to inhibit it [1-3].<br/>

ROCK phosphorylates MLC, activating it [4-6].<br/>

IL21R induces STAT3 activation [1-4]

IL10R induces STAT3 activation [1-4]

IL27R&nbsp;induces STAT3 activation [1-4]

IL6R&nbsp;induces STAT3 activation [1-4]

IL23R&nbsp;induces STAT3 activation [1-4]

IL4R phosphorylates STAT6 [1-3]

Carma 1 recruits the heterodimer of BCL10 and Malt1 to create lipid rafts. [1-3]

Cas binds to Crk to form and active Cas/Crk scaffold complex [1-3].

Phoshphorylated paxillin creates a binding site for Crk. Crk becomes active upon binding paxillin [4-6].<br/>

IL-9 binds to the heterodimeric receptor ( IL-9 receptor ).[1-3]

<strong></strong><strong></strong>Upon IL-9 stimulation, the tyrosine kinases JAK3 and JAK1, associated\r\n with IL-9R, becomes &nbsp;activated and phosphorylate the IL-9R on a single tyrosine residue. [1-3]<br/>

JAK2 phosphorylates the tyrosine residues of STAT4 leading to activation. [2-5]

Tyk2 phosphorylates STAT4 [2-5]

GATA3 inhibits STAT4. This is thought as an intermediate to shut down interferon gamma signaling. [1,2,6]

P38 induces serine 721 phosphorylation of STAT4. [7-10]

Adenyl_cylcase creates cAMP from ATP. [1-3]

G alpha 12/13 receptor binds to activates RhoGEF [1-4].<br/>

The FAT region of FAK binds to RhoGEF to activated it [5-7].<br/>

CAV1 links integrin subunits to the to the Tyrosine kinase FYN [2,6,7].<br/>

CD3-TCR complex mediates phosphorylation of FYN [3,5,6].<br/>

CD3-TCR Complex mediates the proximal phosphorylation of FYN [5]. Specifically, the gamma and epsilon chains of CD3 phosphorylate FYN when TCR is active [3,6].<br/>

STAT3 cooperates with TGFBR to activate RORGT. [1-4]

RORGT is thought to regulate itself after activation [2]

TGFBR cooperates with TGFBR to activate RORGT. [1-4]

RhoGEFs increase binding of GTP-Cdc42, activating Cdc42 [4,5,7].<br/>

GEFs <span id="">bind to inactive Cdc42 (Cdc42-GDP) to form a Cdc42-GEF \r\nbinary that un-stabilizes the GDP binding; the abundant cytosolic GTP \r\nreplaces GDP in Cdc42 and form active Cdc42 (Cdc42-GTP) [1-3].<br/></span>

Activated <span class="highlight" style="background-color:">Rac</span> binds to the amino terminus of <span class="highlight" style="background-color:">IRSp53 [1-3].<br/></span>

IL12RB mediates tyrosine phosphorylation of Tyk2 when IL12RB1 &amp; 2 are active [1-4].

IL12RB mediates tyrosine phosphorylation of Tyk2 when IL12RB1 & 2 are active [1-4].<br/>

The active GTP-bound form of RhoA binds to ROCK to activate it [1-3].<br/>

G alpha Q binds to carboxyl-terminal region between residue 881 and the most <span class="highlight" style="background-color:">carboxyl-terminal</span> 10 kDa of PLC-beta <span class="highlight" style="background-color:">1 and activates it [1-3].<br/></span>

STAT1 and STAT3 cooperate to activate IL22 [1-3]<br/>

STAT5 activates IL22 [1-3]

<span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">STAT1 and STAT3 cooperate to activate IL22 [1-3]</span>

STAT4 activates IL22 [1-3]

Upon Rac1-IRSp53 binding, the VCA region of WAVE2 is exposed and causes Arp2/3 complex activation [4].<br/>

Arp2/3 complex binds to WASp within the C subdomain at residue Met 474 and within the A subdomain to Trp 500 [2].<br/><br/>The conserved VCA domain of WASP proteins <span class="highlight" style="background-color:">activates</span> <span class="highlight" style="background-color:">Arp2/3</span> complex by inducing conformational changes and delivering the first <span class="highlight" style="background-color:">actin</span> monomer of the daughter filament [3].

RasGTP binds to the allosteric pocket of Sos. This priming enhances <span class="highlight" style="background-color:">SOS</span> activity and creates a positive RasGTP-<span class="highlight" style="background-color:">SOS</span> feedback loop for <span class="highlight" style="background-color:">Ras</span> activity. Sos complexes to Ras to activate it [7].<br/>

<span style="font-size: 12px;">RasGRP orchestrates <span class="highlight" style="background-color:">Ras</span> signaling by activating <span class="highlight" style="background-color:">Ras</span> directly and by facilitating priming of <span class="highlight" style="background-color:">SOS</span> with RasGTP that binds the allosteric pocket [7].<br/><br/>TCR-induced production of DAG results in the activation of two major \r\npathways involving Ras and PKC. Ras is a guanine nucleotide-binding \r\nprotein and is required for the activation of the serine-threonine \r\nkinase Raf-1. [Smith]</span>

PAK phosphorylates MEK1/2 on Serine 298 to activate it [4-6].<br/>

B-RAF phosphorylates MEK1/2 [7-9].<br/>

Raf-1 that leads to the activation of the mitogen-associated protein \r\nkinases (MAPKs) extracellular signal-regulated kinase 1 (Erk1) and Erk2.[1-3]

<span class="highlight" style="background-color:">RIAM</span> contains a RA-like (Ras association) \r\ndomain, a PH (pleckstrin homology) domain, and various proline-rich \r\nmotifs.RIAM binds to the GTP-bound Rap1 and becomes activated [1-3].<br/>

cofilin, an actin binding protein, facilitates the dissociation of actin monomers from F-actin pointed ends [6-8].<br/>

Arp2/3 Nucleates Actin filaments [1-7].<br/>

Arp2/3 uses a monomer of G actin for the initial nucleation of actin, forming f-actin [1-7].<br/>

STAT5_high starts cell proliferation. [1]

Once a cell is proliferating, this node can self maintain to start clonal expansion of the cell. &nbsp;[1]

<div><span style="font-size: 10pt;">Ca2+ released in the cytosol from IP3 signaling disrupts the inhibitory effect of calmodulin which leads to the activation of Calcineurin. [1-4]</span></div>

Ras is a guanine nucleotide-binding protein and is required for the activation of the serine-threonine kinase Raf-1 [1-4].<br/>

PAK phosphorylates LIMK on Threonine 508 [4-6].<br/>

ROCK phosphorylates LIMK on Threonine 508 [1-3].<br/>

A higher level of activity from STAT5 is needed to sufficiently inactivate IL4RA. [1,2]

The higher activity of IL4RA is needed to promote a more reactive receptor. [1-3]

External source of Interleukin 4 that binds the highly reactive receptor state. [1-3]

<span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">Internal source of Interleukin 4 that binds the highly reactive receptor state. [1-3]</span>

The Common Gamma Chain is part of the IL4 receptor and its activity is required for IL4 signaling. [1-3]

Lck phosphorylates CD3 ITAM \r\nmotifs and amplifys the signal through the co-receptor CD4 to which\r\n it is associated [1-5].<br/>

STAT3 activates IL21 through IL6 signaling. [1-4]

Proliferation is required along with transcription factors STAT3 and NFAT for IL21 production. [1-4]

Transcription factor NFAT is required in cooperation with proliferation and STAT3 for IL21 production. [1-4]

IL18_e binds to IL18R1. [1-3]

Tyrosine phosphorylated STAT3 induces SOCS3 expression [1-3].<br/>

<span class="highlight" style="background-color:">Zap</span>-<span class="highlight" style="background-color:">70</span>&nbsp; <span class="highlight" style="background-color:">phosphorylates</span> <span class="highlight" style="background-color:">LAT</span> on <span class="highlight" style="background-color:">tyrosine</span> residues at positions 226, 191, 171, 132 and 127 [1-3].<br/>

TGFBR activates SMAD3. [1-3]

CD3 and TCR is a complex. Upon the TCR portion becoming activated by APC and MHC II, CD3 chains are activated [1-3].<br/>

<div><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;">Upon IP3 receptor binding. Ca2+ stores in the Endoplasmic R</font><font face="Arial, Verdana" size="2">eticulum are&nbsp;released&nbsp;into the cytoplasm. [1-3]</font></div><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;"><br/></div>

STAT3 activates IL10 by binding to its promoter. [1,2,4]

Proliferation is required in cooperation with NFAT and GATA3 or STAT3 to produce IL10 [1-3]

Transcription factor NFAT is required in cooperation with proliferation and GATA3 or STAT3 to produce IL10. [1-3]

GATA3 activates IL10 through the remodeling of the IL10 locus. [1-3]

The<font size="2"> G(alpha)<span class="highlight" style="background-color:">12</span>/<span class="highlight" style="background-color:">13</span> <span class="highlight" style="background-color:">G protein-coupled receptor is activated up specific ligand binding [1-3].<br/></span></font>

CAV1 activates NOS2A [1].<br/>

This node indicates proliferation of the cell and works in conjunction with FOXP3 and NFAT in the production of TGFB. [1]

The transcription factor NFAT is believed to cooperate with FOXP3 and proliferation in the expression of TGFB. [1]

It is believed that FOXP3 has an effect in the role TGFB expression. [1]

Upon GTPase binding, PAK1 undergoes a conformational\r\n change that separates the autoinhibitory domain \r\nfrom the kinase domain. This induces kinase activity and \r\nautophosphorylation at several sites, including the Thr-423 site in the \r\nactivation loop\r\n to stabilize the active state [1-3,7,8].

Nck recruits PAK through its SH3 domain [4-6].<br/>

Upon GTPase binding, PAK1 undergoes a conformational\r\n change that separates the autoinhibitory domain \r\nfrom the kinase domain. This induces kinase activity and \r\nautophosphorylation at several sites, including the Thr-423 site in the \r\nactivation loop\r\n to stabilize the active state [1,7,8].

Crk has an N-terminal SH3 domain that binds and interacts with the guanine nucleotide exchange factor CG3 [1-4].<br/>

Any antigen presenting cell (Macrophage, Dendritic, and B cells) is able\r\n to display antigen to the T cell via it's MHC II. Antigen then triggers\r\n the TCR. For full activation of the TCR, there must be a secondary, \r\ncostimulatory signal, which is provided when B7 from the APC binds to \r\nCD28. The second signal allows the TCR to become fully activated [5-7].

Any antigen presenting cell (Macrophage, Dendritic, and B cells) is able to display antigen to the T cell via it's MHC II. Antigen then triggers the TCR. For full activation of the TCR, there must be a secondary, costimulatory signal, which is provided when B7 from the APC binds to CD28. The second signal allows the TCR to become fully activated [1-7].<br/>

Interleukin 4 receptor alpha is a subchain of the interleukin 4 receptor. [1] Its activity is required to respond to interleukin 4.&nbsp;

External source of interleukin 4.

Interleukin 4 binds with IL 4 receptor when CGC and IL4A are in their active state. [1] The naming of this node denotes internally produced interleukin 4 from the model.

CGC is the common gamma chain and is required for numerous interleukin receptors. [1] IL4R requires the activity of CGC to bind IL4. [1]

CD28 and TCR activate NFAT after engagement of these ligands. [1-3]

Calcineurin activates NFAT through dephosphorylation. [1]

CD28 and TCR activate NFAT after engagement of these ligands. [1-3]

P38 is coupled to the activation of NFAT in cooperation with DLGH1 and Calcineurin because of its phosphorylation at Tyr323. [5-6]

GSK3-b inhibits NFAT by phosphorylation. [3]

Sos is recruited to the membrane by adapter Grb2. The N-terminal SH3 \r\ndomain of Grb2 binds to the C-terminal proline rich region of SOS. Grb2 \r\nSH2 domain properly localizes the complex to the membrane by \r\nbinding to phosphorylated tyrosines on receptors or membrane-anchored \r\nadapters [1-6].

Galpha_iR has a negative impact on the activation of adenyl cyclase [1-3]

GalphaS_R is the stimulatory GPCR that activates adenyl cyclase to carry out cAMP signaling. [1-3]

External&nbsp;source of Transforming growth factor beta binds with the receptor to activate the TGFB pathway. [1-3]

Internal source of Transforming growth factor beta binds with the receptor to activate the TGFB pathway. [1-3]

TAK1 phosphorylates MKK7 to activate it [1-3].<br/>

STAT5 and STAT6 cooperate to inhibit IL2. [1,5,6]

STAT5 and STAT6 cooperate to inhibit IL2. [1,5,6]

NFKB is an activator of IL2 in the absence of TBET. [1,2,6] If TBET is also active, NFKB cooperates with TBET to inhibit IL2. [1,2,6]

TBET cooperates with a subunit of NFKB to inhibit IL2. [1,2,6]

Production of IL2 requires NFAT which is blocked by FOXP3. [1,2,4,6]

FOXP3 inhibits IL2 production by blocking the activation of NFAT. [1,2,4,6]

ICOS is a costimulator that is activated by an antigen presenting cell. [1-3]

TBET activates RUNX3 to further IFNG signaling. [1,2,4]

GATA3 inhibits RUNX3. [3-5]

IL12 has an influence on expression for GADD45G. [1-4]

CD3 can activate GADD45G although the reaction is unclear. [1-4]

IL22 binds to IL22R. [1-3]

PIP3_345 is a product of PI3K enzymatic synthesis upon PI3K activation [1-4].<br/>

activation of PKA is cAMP-dependent [1-3].<br/>

STAT6 induces the up-regulation of GATA3. [3,4,8]

Dec2 is first activated by GATA3 initially and Dec2 helps GATA3 to maintain itself in a Th2 determined lineage. [5-7]

TBET inhibits GATA3 by binding to GATA3 promoter sites. [6-9]

STAT3 activates IL23 in an IL6 mediated manner. [1-3]

Proliferation is needed to begin signaling. [1,2]

NFAT is required for IL23 signaling. [1,2]

IL27RA is a subunit of IL27R and its activity is required for interleukin 27 signaling. [1-3]

Interleukin 27 binds to the interleukin 27 receptor to activate it. [1-3]

GP130 is a subchain and is required for interleukin 27 signaling. [1-3]

Internal source of interleukin 21 that binds to IL21R [1-4]

External source of interleukin 21 binds to IL21R [1-4]

Common gamma chain that is required in cooperation with IL21R for interleukin 21 signaling. [1-3]

Subchain that is required in cooperation with IL21R for interleukin 21 signaling. [1-3]

PLCg is responsible for the production of the second messenger IP3[1-3]<br/>

<font face="Verdana, Geneva, sans-serif"><span style="font-size: 11px;">IKB suppresses NFKB by binding to inactivate [1-4]</span></font>

FOXP3 suppresses NFKB signaling. [2-4]

PLCb hydrolyzes PIP2 to IP3 and diacylglycerol (<strong>DAG</strong>) [5-7].<br/>

<span class="highlight" style="background-color:">PLC gamma</span><span class="highlight" style="background-color:"></span> <span class="highlight" style="background-color:">hydrolyzes</span> <span class="highlight" style="background-color:">phosphatidylinositol 4,5-bisphosphate</span> into <span class="highlight" style="background-color:">diacylglycerol (DAG) [1-4].<br/></span>

IFNG_e is the external source of IFNG. IFNG is produced from active T helper 1 cells. [1] IFNG_e activates IFNGR as long as the subchains IFNGR1 and IFNGR2 are active. [1-3]<div><br/></div>

IFNG activates IFNGR upon binding as long as IFNGR1 and IFNGR2 are active. [1-3]

IFNGR1 is a subchain of the IFNGR. [1-3]

IFNGR2 is a subchain of the IFNGR. [1-3]

Phosphorylation of <span class="highlight" style="background-color:">Shc</span> on <span class="highlight" style="background-color:">tyrosine</span> residue Y317 allows binding to the SH2 domain of <span class="highlight" style="background-color:">Grb2 [7-9]<br/></span>

ZAP70 phosphorylates Tyr residue in LAT, which then recruits Gads, Grb2, and PLC gamma [1-3].<br/>

CD26 mediates phosphorylation of CAV1 [1-3].<br/>

STAT3 and RORGT cooperate to activate IL23R. [1,2] It is thought that they are needed for the sub units. [1,2]

External source of interleukin 23 that binds the receptor. [1-3]

RORGT and STAT3 cooperate to activate IL23R. [1,2] It is thought that they are needed for the sub units. [1,2]

Internal source of Interleukin 23 that binds the receptor. [1-3]

IL12RB1 is a subchain that interacts with GP130 to start IL 23 signaling. [1-3]

GP130 is a subchain required for IL23R activity. [1-3]

Phosphorylated ITAMs become docking sites for the tandem SH2 domains of ZAP-70, leading to phosphorylation [1-3].<br/>

ZAP-70 has an SH2 domain that interacts with the epsilon CD3 chain and zeta TCR chain [4-6].<br/>

<span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">IL2RA is a sub chain of IL2R. Its activity is not required for a normal IL2 response. Upon activation if IL2RA, the high affinity response becomes active. [1]</span>

<span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">IL2 is produced by the model in normal IL2 response. IL2R uses IL2 in the event that IL2_E is absent. [1]</span>

<span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">IL2RB is a subchain of IL2R. Its activity is required for proper activation if IL2R. [1]</span>

<span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">IL2_e is required for IL2R to become active. IL2_e is an external source of Interleukin-2 and binds IL2R when the appropriate sub-chains are active. [1]</span>

<font face="Arial, Verdana" style="color: rgb(79, 79, 79); line-height: 14.390625px; text-align: justify; background-color: rgb(255, 255, 255);">CGC is a sub-chain of IL2R. Its activity is required to properly activate IL2R. [1] &nbsp;CGC is known to be a common chain for Interluekins 2, 4, 7, 9, 15, and 21</font><font color="#2e2e2e" face="Arial Unicode MS, Arial Unicode, Arial, URW Gothic L, Helvetica, Tahoma, sans-serif" style="line-height: 14.390625px; text-align: justify; background-color: rgb(255, 255, 255);"><span style="line-height: 20px; word-spacing: -1px;">. [3]</span></font>

Interleukin 27 receptor induces STAT1 activation in T cells. [4-6]

Interferon beta receptor induces STAT1 activation in T cells. [4-6]

Interferon gamma receptor induces STAT1 activation in T cells. [4-6]

SOCS1 suppresses STAT1 signaling in T Cells. [1,7,8]

GATA3 strongly binds to IRF4 [1-3].<br/>

SHP-2 undergoes tyrosine phosphorylation through the IL-2 receptor beta chain [1,5,6].<br/>

GAB2, the major SHP2 binding protein, becomes tyrosyl-phosphorylated and associates with SHP2 [2-4].<br/>

Fyn binds, via its SH3 domain, to Shc. Shc is subsequently phosphorylated at tyrosine 317 [2-6].<br/>

Shc is phosphorylated by the Tyrosine residue 338 by the IL-2 beta chain receptor [1,5,7].<br/>

IL2R phosphorylates SHC1 [1,5,7]

IL10RA is a subchain of IL10R. [1]

Internal source of Interleukin 10. Binds with IL10R in the presence of IL10RA and IL10RB. [1]

External source of Interleukin 10. Binds with IL10R in the presence of IL10RA and IL10RB. [1]

IL10RB is a subchain of IL10R. [1]

CD28 activatesPI3K [1-4].<br/>

SHP2 mediates PI3K activation [12-14].<br/>

ICOS recruits the p50alpha subunit of PI3K and activates it [1-4].<br/>

FAK binds to PI3K and moderately activates it [5-7].<br/>

IL-2 activates PI3K [11,18,19].<br/>

Phosphorylated GAB2 binds PI3K and activates it [8-10].<br/>

Ras GTPase activates PI3K [15-17].<br/>

TCR signaling through Lck and ZAP-70 leads to the phosphorylation of SLP-76 at tyrosines 112, 128, and 145, creating binding\r\n sites for Vav-1 [1-4].<br/>

Phophorylated Tyrosine residues of LAT, specifically Y171 and Y132, are necessary for the association and activation of PLCg [1,2,6].<br/>

Phosphorylation of <span class="highlight" style="background-color:">PLC</span>-gamma1 by <span class="highlight" style="background-color:">Itk</span> requires a direct, phosphotyrosine-independent interaction between the Src homology 2 (SH2) domain of <span class="highlight" style="background-color:">PLC</span>-gamma1 and the kinase domain of <span class="highlight" style="background-color:">Itk [4,8,9].<br/></span>

Phosphorylation of ZAP-70 on Tyrosine319 activates PLC gamma by association of the SH2 domain of ZAP-70 [3,7,8].<br/>

IL-9 receptor ligation results in auto and/or trans-phosphorylation of Janus\r\nkinases 1 and 3 ( JAK1 and JAK3 ). [1-3]&nbsp;<br/>

<span id="species:viewSpeciesDescription" style="font-size: 12px;">Upon SOCS3 phosphorylation, JAK1 is polyubiquinated in a phosphorylation-dependent manner [3-5].<br/></span>

IL-22 binding to IL-22 receptor complex leads to the\r\nactivation of the receptor-associated Janus kinases JAK1. [1-3]<br/>

IL2R binds to JAK1 [1,6,7]

JAK3 phosphorylates JAK1 [1,6,7]

<span style="font-family: Verdana, Geneva, sans-serif; font-size: 10.909090995788574px; background-color: rgb(255, 255, 255); ">MEKK4 binds to a docking site on MEK6 and phosphorylates it [1-3].<br/></span>

TBET is described as an auto activator that is dependent upon IFNG and STAT1. [4] In the absence of IFNG and STAT1, TBET levels were reduced, but maintained activation. [4]

CD4+ T helper cells lacking STAT1 were unable to sufficiently activate TBET. [4] STAT1 is vital to initial TBET activation, but not required for subsequent activity. [4]

TBET mRNA is downregulated by virus induced GATA3 expression in vivo in the murine model. [1]<br/>

Raf-1 that leads to the activation of the mitogen-associated protein \r\nkinases (MAPKs) extracellular signal-regulated kinase 1 (Erk1) and Erk2.[1-4]<br/><br/>MEK1/2-mediates phosphorylation of ERK1/2 on the\r\n Thr-Xaa-Tyr signature motif (Thr202 and Tyr204) [1-4].<br/>

SOCS3 inhibits JAK2 by binding to the STAT4 docking site on JAK2. [5-7]

<span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">IL12RB2 (as part of IL12R) binds with JAK2 to activate. [1-3]</span>

IL12RB1 (as part of IL12R) binds with JAK2 to activate. [1-3]

Upon T cell activation, IKB is phosphorylated by the IKB kinase (IKK) complex, ubiquitinylated, and degraded, allowing NFKB to translocate into the nucleus, where it actives genes involved in the function, survival, and homeostasis of T cell. [1-3]

<span style="font-family: Verdana, Geneva, sans-serif; font-size: 10.909090995788574px; background-color: rgb(255, 255, 255); "><br/><br/></span><span style="font-family: Verdana, Geneva, sans-serif; font-size: 10.909090995788574px; background-color: rgb(255, 255, 255); ">GADD45 beta physically interacts with MEKK4 and increases its activity if GADD45G is also bound to MEKK4 [1-4].</span><br/>

<br style="font-family: Verdana, Geneva, sans-serif; font-size: 10.909090995788574px; "/><span style="font-family: Verdana, Geneva, sans-serif; font-size: 10.909090995788574px; background-color: rgb(255, 255, 255); ">GADD45 beta physically interacts with MEKK4 and increases its activity if GADD45G is also bound to MEKK4 [1-4].<br/></span>

<span style="font-family: Verdana, Geneva, sans-serif; font-size: 10.909090995788574px; background-color: rgb(255, 255, 255); ">MEK3 has a conserved docking site and can be activated by MEKK4 by phosphorylation [1-3].<br/></span>

Bcl10_Malt1 are recruited to Carma1 to form a complex that builds a lipid raft and links IKK to IKBa. [1-4]

Carma 1 recruits and associates with Bcl10_Malt1 to create the CMB complex that builds a lipid raft and links IKK to IKBa. [2][3]

CAV1 Y14 activates RhoA [4-6].<br/>

RhoGEF promotes formation of the active GTP-bound RhoA [1-3].<br/>

SHC1 activates Gab2 through SHP2. [1-3]

Grb2 activates GAB2 through binding. [1-3]

SYK&nbsp;&nbsp;phosphorylates STAT5[3-5]

Lck phosphorylates STAT5[3-5]

IL15R activates STAT5. [1-3]

IL2R&nbsp;&nbsp;activates STAT5. [1-3]

JAK1 autophosphorylates STAT5. [3-5]

IL4R&nbsp;&nbsp;activates STAT5. [1-3]

Vav catalyzes the nucleotide exchange of rac1, thereby activating it [3].<br/>

<span class="highlight" style="background-color:">paxillin-Crk-DOCK180</span> <span class="highlight" style="background-color:">signaling</span> <span class="highlight" style="background-color:">complex</span> controls rac1 activation [4-6].<br/>

Y221 site in CrkII <span class="highlight" style="background-color:">regulates</span> <span class="highlight" style="background-color:">Rac</span> <span class="highlight" style="background-color:">membrane</span> translocation [4-6].<br/>

NOS2A activates rac1 [2].<br/>

was binds, via the GTPase binding domain, to rac1 and activates it [2,7,8].<br/>

Nck is recruited to Tyrosine phosphorylation sites on SLP-76 [1-3].<br/>

CD28 activates autophosphorylation of Lck [6-7].<br/>

IL2RB binds Lck, which is subsequently phosphorylated by JAK3 [8-10].<br/>

<font face="Arial" size="2">Lck associates </font><font face="Arial" size="2">through its distinctive ammo-terminal segment with the cytoplasmic tails of T-cell co-receptor CD4, and is activated by autophosphorylation at Tyr394 [1-5].<br/></font>

IL2RB binds Lck, which is subsequently phosphorylated by JAK3 [8-10].

RAP1 activates BRAF through binding. [1-3]

AKT inhibits GSK3-B by phosphorylation. [1-5]

LIMK phosphorylates cofilin on Ser3 [1-4].<br/>

RIAM has a RA-like (Ras association) domain, a PH (pleckstrin homology) domain, and various proline-rich motifs. RIAM is able to bind and activated profilin [1-3].<br/>

Src associates with the cytoplasmic domain of activated beta intergins and is subsequently activated [7-9].<br/>

FAK phosphorylated on Tyrosine residue 397 mediates binding of Src via the SH2 domain [2,4,5].<br/>

PIP3_345 recruits PDK1 to the plasma membrane and serves a docking site [1-3].<br/>

TRAF6 associates with NIK via the conserved WKI motif within the TRAF domain [1-3].<br/>

Cas is tyrosine phosphorylated by FAK upon beta integrin engagement [1-4].<br/>

FAK has two proline rich sequences (PR1 and PR2) located between the FAT and catalytic domains that interact with the SH3 domain of Cas [1]. FAK tyrosine phosphorylates Cas [2-4].<br/>

TRAF6 is a ubiquitin ligase that activates kinase activity of TAK1 by binding and ubiquitination [1-3].<br/>

<span style="font-size: 12px;">Localized PIP</span><font size="2">3</font><span style="font-size: 12px;">&nbsp;generation serves as a docking site for the PH\r\n domains of PDK1 and its\r\n target Akt. [1-3]</span>

IRF1 promotes a higher level of activation of IL12RB1. [4-6]

IL12_e is the external source of Interleukin 12 that is binds to IL12RB1. [1-3]

IL12_e has an influence on expression of GADD45B. [1-4]

TCR can activate GADD45B through CD3. [1-4]

The dimeric tail of CD26 in the cytosol binds with Carma1 to activate. [1-3]

Carma1 is phosphorylated and activated by PKC. [1-3]

CD28 becomes activated up B7 ligand binding [1-6].<br/>

CD28 detects an antigen presenting cell and provides co-stimulatory assistance to the T cell receptor in the presence of an antigen presenting cell. [1] [2]

STAT4 induces transcription of the ERM gene. [1,2]

FAK activation and phosphorylation is dependent on integrins binding to extra cellular ligands. FAK colocalizes with integrins in focal contacts and is autophosphorylated on Tyrosine residue 397 [1-7].<br/>

PKC contains two cysteine-rich, zinc finger–like motifs, that are binding sites of DAG. When DAG binds, PKC becomes active.<br/>

STAT6 inhibits IL17 by the binding of its promoter. [1-3]

STAT5 inhibits IL17 by the binding of its promoter. [1-3]

* Add any laboratory findings here. You can use bullet points to separate different findings. <br>* Additional findings.

Proliferation is required for the production of IL17 in the thought that the cell is in clonal expansion. [2]

NFKB cooperates with STAT3 and RORGT through transcriptional regulation to promote IL 17 production. [1-5]

STAT1 inhibits IL17 by the binding of its promoter. [1-3]

RORGT has an influence on expression of IL17 and cooperates with STAT3 through transcriptional regulation of IL17. [1-5]

NFAT activity is required for the production of IL17 [2]

FOXP3 blocks transcription of interleukin 17 by binding to its promoter. [1-3]

Interleukin\r\n18 receptor 1 ( IL-18R1 ), activated by IL-18, recruits Interleukin-1\r\nreceptor-associated kinase 1 ( IRAK1 ) and TNF receptor-associated factor 6 (\r\nTRAF6 ). TRAF6 activates Mitogen-activated protein kinase kinase kinase 14\r\n( NIK(MAP3K14) ). This leads to subsequent activation of NF-kB, which\r\npromotes transcription of GADD45 beta [1-4].<strong><br/></strong>

MEKK4 phosphorylates MEK4 [1-3].<br/>

IFNB ligand for the IFNB receptor [1-3]

IL2R_HIGH activates STAT5_HIGH. [1-3]

IL4R_HIGH activates STAT5_HIGH [1-3]

G(alpha)Q is activated by receptor-mediated activation induced by ligand [1-3].<br/>

CD4 binds to the constant region of MHC class II to stabilize the interaction with TCR [3,4].<br/>CD4 binds MHC at the superdimer interface [2].<br/>

CD4 associates the with TCR-CD3 complex upon antigen binding [1,4-6].

CD4 associates the with TCR-CD3 complex upon antigen binding [1,4-6].<br/>

SYK associates and is activated by IL2R [1-3].<br/>

SLP-76 with phosphorylated N-terminal Tyrosines recruit Itk (via Itk's SH2 domain) [1-4].<br/>

Src binds to was to activate it [1,2].<br/>

Two MAPKKs, MKK4 and MKK7, have been identified as JNK activators. \r\nGenetic studies demonstrate that MKK4 and MKK7 serve nonredundant \r\nfunctions as activators of JNK in vivo. [1,5-9]<br/>

The SH3 domain of Crk is required for JNK activation by rac1 [2-4].

MEK4 acts on JNK to activate it [1,5-9].<br/>

The SH3 domain of Crk is required for JNK activation by rac1 [2-4].<br/>

GATA3 induces the gene Bhlhe41 that encodes for Dec2. [1-3]

External source of Interleukin 6. Binds with IL6R when GP130 and IL6RA are active. [1]

IL6RA is a subchain of the interleukin 6 receptor. [1]

Glycoprotein 130 forms a complex with binded receptors of the IL6 family. [1] Its activity is required for IL6R to respond to interleukin 6. [1]

<span style="color: rgb(79, 79, 79); font-family: Arial, sans-serif; font-size: 12px; line-height: 18px; orphans: 3; widows: 3; background-color: rgb(255, 255, 255);">A higher level of activity from STAT5 is needed to sufficiently activate IL4RA_High. [1,2]</span>

LAT-associated Gads bring adapter protein SLP-76 (LCP-2) to rafts, where it becomes a substrate for ZAP70. [1-4]<br/><br/>

Upon TCR stimulation, ZAP-70 phosphorylates 3 N-terminal Tyrosines of SLP-76 [6].<br/>