Itk

Itk (Interleukin-2-inducible T-cell kinase) is a Tec family tyrosine kinase that mediates signaling processes after T cell receptor engagement. Activation of Itk requires recruitment to the membrane via its pleckstrin homology domain, phosphorylation of Itk by the Src kinase, Lck, and binding of Itk to the SLP-76/LAT adapter complex. After activation, Itk phosphorylates and activates phospholipase C-gamma1 (PLC-gamma1), leading to production of two second messengers, DAG and IP3. IP3 and DAG stimulate the release of calcium ions from the endoplasmic reticulum and activate Protein Kinase C, respectively. In addition, Itk regulates the development of Th2 cells and their subsequent cytokine secretion, thereby modulating the immune response.

Studies have shown that ITK is involved in the pathogenesis of autoimmune diseases as well as in carcinogenesis. The loss of ITK or its activity either by mutation or by the use of inhibitors led to a beneficial outcome in experimental models of asthma, inflammatory bowel disease and multiple sclerosis among others. In humans, biallelic mutations in the ITK gene locus result in a monogenetic disorder leading to T cell dysfunction, etc. These findings put ITK in the strong focus as a target for drug development.