ITK
Description
The ITK (IL2 inducible T cell kinase) is a protein-coding gene located on chromosome 5.
ITK is a gene that encodes a mammalian protein called IL2-inducible T-cell kinase.
ITK is a tyrosine kinase that plays a crucial role in the adaptive immune response. It regulates the development, function, and differentiation of conventional T-cells and nonconventional NKT-cells. When antigen-presenting cells (APCs) activate the T-cell receptor (TCR), ITK is recruited to the cell membrane near the stimulated TCR, where it is phosphorylated by LCK. This phosphorylation leads to ITK autophosphorylation and full activation. Once activated, ITK phosphorylates PLCG1, activating this lipase and leading to the cleavage of its substrates. This process triggers calcium release from the endoplasmic reticulum into the cytoplasm, and the nuclear activator of activated T-cells (NFAT) translocates into the nucleus to perform its transcriptional functions. ITK also phosphorylates two essential adapter proteins: the linker for activation of T-cells (LAT) protein and LCP2. These events recruit numerous signaling molecules, such as VAV1, ultimately leading to lymphokine production, T-cell proliferation, and differentiation. ITK is essential for TCR-mediated calcium responses in gamma-delta T-cells and may also be involved in modulating the transcriptomic signature in the Vgamma2-positive subset of immature gamma-delta T-cells. It phosphorylates TBX21 at 'Tyr-530' and mediates its interaction with GATA3. ITK forms homo-oligomers, which negatively regulate kinase activity. It interacts with PPIA/CYPA, regulating TCR signal strength through a proline-directed conformational switch. ITK also interacts with THEMIS and FASLG, and its interaction with VAV1 is important for VAV1 localization and TCR-induced actin polarization. Finally, it interacts with TBX21.
ITK is also known as EMT, LPFS1, LYK, PSCTK2.
