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T Cell Receptor Signaling Pathway

T cell receptors (TCR) play a key role in functioning of T cells and formation of the immunological synapse. It provides connection between T cell and the antigen-presenting cell (APC). TCRs activation promotes a number of signaling cascades that ultimately determine cell fate through regulating cytokine production, cell survival, proliferation, and differentiation. Activation of T lymphocytes is a key event for an efficient response of the immune system.TCR activation is regulated by various co-stimulatory receptors. CD28 provides an essential co-stimulatory signal during T-cell activation, which augments the production of IL-2 (Interleukin-2), increases T-cell proliferation and prevents the induction of anergy and cell death. CD28 ligation by B7-1 or B7-2 helps in bringing the T-Cell and Antigen Presenting Cell membranes into close proximity. Besides CD28, many other transmembrane receptors also modulate specific elements of TCR signaling,such as CD45 and CD4. An early event in TCR activation is phosphorylation of immunoreceptor tyrosine-based activation motifs (ITAMs) on the cytosolic side of the TCR/CD3 complex by lymphocyte protein tyrosine kinase (Lck). The CD45 receptor tyrosine phosphatase modulates the phosphorylation and activation of Lck and other Src family tyrosine kinases. TCR activation also leads to cytoskeletal rearrangements through the activation of GTP-binding proteins Rac and PAK, downstream of ZAP70. Negative regulation of TCR signaling is also significant, in order to keep a check on the hyperactivation of immune response associated with the pathway. SIT (SHP2-interacting transmembrane adaptor protein) is a recently identified transmembrane adaptor protein, which interacts with the SHP2 (SH2-containing protein tyrosine phosphatase-2) via an ITIM (immunoreceptor tyrosine-based inhibition motif), and the complex acts as a critical negative regulator of TCR-mediated signaling. In addition, CTLA4 (cytotoxic T-lymphocyte antigen-4) also negatively regulates T-cell activation. The transmembrane protein CTLA4 also serves as a natural inhibitor. Once T-cells become activated, by whatever disease process is turning them on, the body has a natural process to turn down the T-cell pathways so that it does not get out of control.

CD28 CD4 CD45 TCR/CD3 Complex CRAC Channel PI3K Lck Zap-70 PIP3 PDK1 Akt PKC CBL2 Bcl10 Malt1 Carma1 TAK1 mTORC1 IKK MKK7 JNK2 Rel NF-kB IkB NF-kB Rel Jun p38 MAPK JNK MKK4/7 GADD45alpha MEKK1 Digh1 Raf MEK1/2 Erk CREB Fos NFAT NFAT NFAT Calcineurin CaMK4 CaM RaS HPK1 SOS Grb2 LAT ADAP NCK SLP76 Vav Plcy1 Wasp Rac CDC42 P38 MAPK Signaling Pathway Cell Proliferation Survival

T Cell Receptor Signaling Pathway from A to Z

ADAP search result
Akt search result
Bcl10 search result
Calcineurin search result
CaM search result
CaMK4 search result
Carma1 search result
CBL2 search result
CD28 search result; Category: CD28
CD4 search result; Category: CD4
CD45 search result; Category: CD45
CDC42 search result
CRAC Channel search result
CREB search result
Digh1 search result
Erk search result
Fos search result
Grb2 search result
HPK1 search result
IkB search result
IKK search result
JNK search result
Jun search result
LAT search result
Lck search result
Malt1 search result
MEK1/2 search result
MEKK1 search result
MKK7 search result
mTORC1 search result
NCK search result
NFAT search result
NF-kB search result
p38 MAPK search result
PDK1 search result
PI3K search result
PIP3 search result
PKC search result
Plcy1 search result
Rac search result
Raf search result
Ras search result
Rel search result
SLP76 search result
SOS search result
TAK1 search result
TCR/CD3 Complex search result; Category: TCR/CD3 Complex
Vav search result
Wasp search result
Zap-70 search result
JNK2 search result
MKK4/7 search result
GADD45alpha search result
P38 MAPK Signaling Pathway search result
Cell Proliferation Survival search result

Thanks to Sino Biological for providing the pathways.