Zeta-associated protein (ZAP-70[pY315⁄pY319]) is a monoclonal antibody specific to human, orangutan, chimpanzee, Rhesus monkey, bovine, Xenopus ZAP-70 [pY315⁄pY319]. This antibody is validated for use in Western Blot, Immunofluorescence, and Flow Cytometry. ZAP-70 [pY315⁄pY319] is encoded by the 7535 gene, also known as zeta-chain (TCR) associated protein kinase 70kDa, SRK, STD, TZK, ZAP-70, FLJ17670, FLJ17679.
Zeta-associated protein (ZAP-70), a 70 kDa member of the Syk tyrosine kinase family, plays a central role in lymphocyte activation and development, and is implicated in several immune disorders (1-3). Upon T-cell antigen receptor (TCR) engagement, ZAP-70 is phosphorylated on tyrosines 292, 315 and 319 in the interdomain B, located between the SH2 and kinase domains (4,5). Phosphorylation of both tyrosines 315 (a Vav-binding site) and 319 (a Lck binding site) enhances ZAP-70 function in mediating lymphocyte signaling, while tyrosine 292 terminates the transient activation of ZAP-70 and attentuates lymphocyte signaling (6,7). Phosphorylation of tyrosines 315 and 319 plays an important role in mediating the positive and negative selection of T cells in thymus (8). TLR9-activated B-cells display elevated ZAP-70 expression levels which correlate with sustained PKB induction (9). Additionally, (–)-epigallocatechin gallate (EGCG), a major catechin found in green tea, binds directly to ZAP-70 resulting in caspase-mediated apoptosis in Jurkat cells (10).
Orchard, J.A., et al. (2004) ZAP-70 expression and prognosis in chronic lymphocytic leukaemia. Lancet 363: 105-111.
Sakaguchi, N., et al. (2003) Altered thymic T-cell selection due to a mutation of the ZAP-70 gene causes autoimmune arthritis in mice Nature 426: 454-460.
Bottini, N., et al. (2002) Activation of ZAP-70 through specific dephosphorylation at the inhibitory Tyr-292 by the low molecular weight phosphotyrosine phosphatase (LMPTP). J. Biol. Chem. 277: 24220-24224.
Di Bartolo, V., et al. (2002) Tyrosine 315 determines optimal recruitment of ZAP-70 to the T cell antigen receptor. Eur. J. Immunol. 32: 568-575.
Magnan, A., et al. (2001) T cell development and T cell responses in mice with mutations affecting tyrosines 292 or 315 of the ZAP-70 protein tyrosine kinase. J. Exp. Med. 194: 491-505.
Gong, Q., et al. (2001) Requirement for tyrosine residues 315 and 319 within zeta chain-associated protein 70 for T cell development. J. Exp. Med. 194: 507-518.
Wu, J., et al. (1997) The Vav binding site (Y315) in ZAP-70 is critical for antigen receptor-mediated signal transduction. J. Exp. Med. 185: 1877-1882.
Kong, G., et al. (1996) Distinct tyrosine phosphorylation sites in ZAP-70 mediate activation and negative regulation of antigen receptor function. Mol. Cell. Biol. 16: 5026-5035.
Bekeredjian-Ding, I. et al. (2008) TLR9-activating DNA up-regulates ZAP70 via sustained PKB induction in IgM+ B cells. J. Immunol. 181: 8267-8277.
Shim, J-H. et al. (2008) (–)-Epigallocatechin gallate regulates CD3-mediated T cell receptor signaling in Leukemia through the inhibition of ZAP-70 kinase. J. Biol. Chem. 283: 28370-28379.