ZAP70

ZAP70 Full Name

zeta-chain (TCR) associated protein kinase 70kDa

ZAP70 Introduction

ZAP70 (Zeta-chain-associated protein kinase 70) is a crucial 70 kDa non-receptor protein tyrosine kinase belonging to the Syk kinase family. It is predominantly expressed in T lymphocytes and Natural Killer (NK) cells, where it serves as an indispensable linchpin in the T cell receptor (TCR) signaling cascade. Upon antigen recognition and binding by the TCR, the Src-family kinase Lck phosphorylates the immunoreceptor tyrosine-based activation motifs (ITAMs) located on the intracellular TCR zeta chains. This phosphorylation creates specific docking sites that recruit ZAP70 to the plasma membrane. Once bound, ZAP70 is itself phosphorylated and fully activated by Lck. The activated ZAP70 then phosphorylates essential downstream adaptor proteins, most notably LAT (Linker for Activation of T cells) and SLP-76. This critical catalytic step effectively translates the extracellular antigen-binding event into a robust intracellular signaling network that ultimately drives T cell activation, proliferation, and differentiation.

Figure 1. Phosphorylation of ZAP-70 is required to initiate T cell receptor signaling. (Source: Yan Q, et al. 2013)

Given its paramount role in adaptive immunity, abnormal ZAP70 function is deeply linked to significant immunological and hematological pathologies. Inherited loss-of-function mutations in the ZAP70 gene result in a rare but severe form of severe combined immunodeficiency (SCID). This specific immunodeficiency is characterized by a complete absence of peripheral CD8+ T cells and the presence of abundant but functionally paralyzed CD4+ T cells, leaving patients highly vulnerable to life-threatening opportunistic infections from infancy. Conversely, the aberrant expression of ZAP70 is a well-established hallmark in certain B-cell malignancies, most notably Chronic Lymphocytic Leukemia (CLL). In the clinical management of CLL, ZAP70 serves as a critical prognostic biomarker. High intracellular expression of ZAP70 in malignant B cells strongly correlates with an unmutated IGHV gene status, enhanced signaling through the B-cell receptor, a more aggressive disease trajectory, and a generally poorer clinical outcome for patients.

Alternate Names for ZAP70

ZAP70; zeta-chain (TCR) associated protein kinase 70kDa; SRK, zeta chain (TCR) associated protein kinase (70 kD); tyrosine-protein kinase ZAP-70; STD; ZAP 70; syk-related tyrosine kinase; 70 kDa zeta-associated protein; 70 kDa zeta-chain associated protein; zeta-chain associated protein kinase, 70kD

• Immunohistochemistry Antibodies for Pathology
• Immunohistochemistry Antibodies for Pathology

• 1. Yan Q, et al. Structural basis for activation of ZAP-70 by phosphorylation of the SH2-kinase linker. Mol Cell Biol. 2013 Jun;33(11):2188-201.
  2. Au-Yeung BB, et al. The structure, regulation, and function of ZAP-70. Immunol Rev. 2009 Mar;228(1):41-57.