Biolegend, 693805, Alexa Fluor® 488 anti-ZAP70 Phospho (Tyr292) 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 Tyr315 and Tyr319 are essential for ZAP70 positive regulation of T-lymphocyte activation whereas Tyr292 has a negative regulatory role. Mutation of Tyr292 to phenylalanine enhanced NFAT induction in response to BCR stimulation, indicating phosphorylation of Tyr292 may promote association of ZAP-70 with a negative regulatory protein. ZAP-70 has been reported to bind Cbl following TCR stimulation and phosphorylation of Tyr292 was required for this interaction, as well as for the negative effect of Cbl on signaling.