Biolegend, 683711, Alexa Fluor® 488 anti-ZAP70 Phospho (Tyr319)/Syk Phospho (Tyr352) Antibody

ZAP70 was identified in TCR-stimulated Jurkat cells. It is an inactive cytosolic tyrosine kinase that is recruited to a transmembrane receptor lacking intrinsic catalytic activity. ZAP70 and the related spleen tyrosine kinase (Syk) play a critical role in T-cell development and activation. This enzyme, which is phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation, functions in the initial step of TCR-mediated signal transduction in combination with the Src family kinases, Lck and Fyn. ZAP70 activation can be regulated by binding to phosphorylated ITAMs of the TCR and by phosphorylation of multiple tyrosine residues on ZAP70. Phosphorylation of Tyr-315 and Tyr-319 are essential for ZAP70 positive regulation of T-lymphocyte activation whereas Tyr-292 has a negative regulatory role. Phosphorylated Y319 is a positive regulator of ZAP70, which triggers the binding of Lck and activation of NFAT and IL-2 induction. The binding of Lck to phosphorylated Y319 promotes Lck mediated phosphorylation of Y493, and facilitates activation of downstream signaling. The importance of Y319 phosphorylation in positive regulation of ZAP70 was confirmed in a mouse model with Y319F ZAP70 mutant expression, which resulted in severe defects in calcium mobilization and thymocyte selection.