Find ITK Products Interaction Network for ITK ITK Details

Related Pathways T Cell Receptor Signaling Leukocyte Extravasation Signaling View All Pathways

Synonyms: EMT, ITK, Itk predicted, LYK, MGC126257, MGC126258, PSCTK2, Tcsk, Tsk

ITK and TCR Signaling

IL2-inducible T-cell kinase (ITK), a member of the Tec family of non-receptor tyrosine kinases is an important early component of TCR signaling. ITK, which contains a pleckstrin homology (PH) domain, is recruited to the plasma membrane by a PI3-kinase-dependent mechanism. Activation of the TCR receptor by antigen binding results in the activation of src family kinases Lck and Fyn and the phosphorylation of ITAM motifs on the CD3 subunits. Zap10 is bound by these immunoreceptor tyrosine-based activation motifs (ITAM) and activated by phosphorylation. Activated Zap10 phosphorylates the docking protein, linker for activation of T cells (LAT). Several molecules bind to LAT including PLCgamma1 and a trimeric complex composed of SLP-76, Vav and ITK. This allows ITK to phosphorylate and activate PLCgamma1.

PLCgamma1 is a phospholipase that cleaves PtdIn(4,5)bisphosphate (PIP2) into inositol triphosphate (IP3) and sn-diacylgylcerol (DAG). IP3 interacts with the IP3receptor associated with the endoplasmic reticulum (ER) and induces the release of calcium. DAG and calcium are activators of conventional protein kinase C isoforms. Membrane DAG regulates various Ras-GTPase guanine nucleotide exchange factors (GEF) directly by recruitment to cellular membranes, as well as indirectly by protein kinase C-mediated phosphorylation. PKCtheta is a novel isoform that is calcium-independent. PKCtheta in synergy with calcineurin activates NFAT in a JNK MAP-kinase-dependent pathway. PKCtheta also activates the nuclear translocation of NFkappaB. NFkappaB and NFAT are required for the gene transcription of IL-2. NFkappaB is also anti-apoptotic.