Tyrosine-protein kinase ZAP-70 (ZAP-70)

Tyrosine-protein kinase ZAP-70 (ZAP-70) is a cytoplasmic non-receptor tyrosine kinase of the Syk family that is essential for T cell receptor (TCR) signaling in lymphocytes[1][2][3]. Upon TCR engagement by antigen, ZAP-70 is recruited to the phosphorylated ITAMs (immunoreceptor tyrosine-based activation motifs) on the CD3-zeta chain, where it becomes activated—primarily by phosphorylation mediated by the Src family kinase Lck—and subsequently phosphorylates key scaffold proteins such as LAT and SLP-76[1][2][3][5]. This triggers a cascade of downstream signaling events that orchestrate T cell activation, proliferation, differentiation, and cytokine production, which are central to the adaptive immune response. ZAP-70 also plays a role in thymocyte development and contributes, to a lesser extent, to B cell signaling[3]. Loss of ZAP-70 function causes an immunodeficiency phenotype (SCID), whereas its aberrant expression or excessive activity is involved in autoimmune diseases and serves as a prognostic biomarker in certain cancers, notably CLL[2][3]. While experimental kinase inhibitors (e.g., staurosporine) have been shown to bind ZAP-70, the target is not yet routinely drugged in the clinic, largely due to its critical role in immune function and the risk of profound immunosuppression[7].

Other names

Zeta-chain-associated protein kinase 70ZAP70Syk-related tyrosine kinaseSTDSRKSTCDTZK70 kDa zeta-chain associated protein70 kDa zeta-associated proteinzeta-chain (TCR) associated protein kinase 70kDazeta-chain associated protein kinase, 70kDzeta chain of T cell receptor associated protein kinase 70kDatyrosine-protein kinase ZAP-70ADMIO2IMD48

ATP-competitive kinase inhibition (by kinase inhibitors like staurosporine)\nInhibition of signal transduction pathways downstream of TCR