Reacts with the C-terminal part of human ZAP- 70 protein tyrosine kinase. The ZAP-70 (zeta- associated protein of 70 kDa) tyrosine kinase was identified as a tyrosine phosphoprotein that associates with TCR zeta subunit and undergoes tyrosine phosphorylation following TCR stimulation. ZAP-70 is a Syk family tyrosine kinase primarily expressed in T and NK cells that plays an essential role in signaling through the TCR. TCR-mediated activation of T cells is crucial to the immune response. In humans, ZAP-70 gene mutations resulting in lower ZAP- 70 protein expression levels or expression of catalytically inactive ZAP-70 proteins, have been identified. ZAP-70 deficiency results in the absence of mature CD8+ T cells and the prevention of TCR-mediated activation of CD4+ T cells, and it can lead to severe combined immunodeficiency. ZAP-70 is a cytosolic protein that migrates at 70 kDa in SDS-PAGE. It contains two N-terminal SH2 domains (Src homology domain 2) and a C-terminal kinase domain. The crystal structure of the ZAP-70 SH2 domains in complex with a TCR zeta subunit peptide was described. During T cell activation, the binding of ZAP-70 SH2 domains to the phosphorylated zeta subunit on the activated TCR complex causes a co-localization with the Lck tyrosine kinase that phosphorylates ZAP-70 on Tyr493 in the activation loop. ZAP-70 autophosphorylates multiple tyrosines in the region between the SH2 domains and the kinase domain, including the binding sites for additional SH2-containing signaling proteins such as SLP- 76, LAT, Lck, PLCgamma1, Vav, Shc, Ras-GAP, and Abl. ZAP-70-mediated activation of these downstream effectors leads to the release of intracellular calcium stores, and the transcription of interleukin-2 and other genes important for an immune response.
Characteristics
Positive Control: Jurkat T cell line. Gene Location: Human chromosome 2q12
Purification
Purified
Immunogen
Bacterially expressed fusion protein representing the C-terminal part (160 amino acids) of human ZAP-70.