ITK (gene)

ITK, also known as Interleukin-2-inducible T-cell kinase, is a non-receptor tyrosine kinase belonging to the Tec family. It is primarily expressed in T cells and natural killer (NK) cells, playing a crucial role in T cell receptor (TCR) signaling and immune responses.

Function:

ITK is essential for the development, differentiation, and function of T cells. Following TCR engagement, ITK is activated by the Src family kinase Lck. Activated ITK then phosphorylates downstream targets, including phospholipase C-γ1 (PLCγ1), leading to the production of inositol trisphosphate (IP3) and diacylglycerol (DAG). These second messengers trigger calcium influx and activation of protein kinase C (PKC), respectively, ultimately leading to the activation of transcription factors such as NFAT, AP-1, and NF-κB. This cascade of events regulates the expression of genes involved in T cell activation, proliferation, cytokine production (e.g., IL-2), and effector functions. ITK also influences T cell polarization and differentiation into various T helper cell subsets.

Clinical Significance:

Mutations or dysregulation of ITK have been implicated in various immune disorders. Loss-of-function mutations in ITK can lead to immune deficiencies, characterized by impaired T cell function and susceptibility to infections. Conversely, aberrant activation or overexpression of ITK has been observed in some autoimmune diseases and cancers, suggesting a potential role in disease pathogenesis. ITK is therefore a target of interest for the development of novel immunomodulatory therapies.

Structure:

ITK is composed of several domains, including an N-terminal pleckstrin homology (PH) domain, a Tec homology (TH) domain, an SH3 domain, an SH2 domain, and a catalytic kinase domain. These domains mediate interactions with other signaling proteins and regulate ITK activity.