ZAP70 Mouse Monoclonal Antibody [A1B5]

Function

Tyrosine kinase that plays an essential role in regulation of the adaptive immune response. Regulates motility, adhesion and cytokine expression of mature T-cells, as well as thymocyte development. Contributes also to the development and activation of primary B-lymphocytes. When antigen presenting cells (APC) activate T-cell receptor (TCR), a serie of phosphorylations lead to the recruitment of ZAP70 to the doubly phosphorylated TCR component CD247/CD3Z through ITAM motif at the plasma membrane. This recruitment serves to localization to the stimulated TCR and to relieve its autoinhibited conformation. Release of ZAP70 active conformation is further stabilized by phosphorylation mediated by LCK. In turn, a large number of signaling molecules are recruited and ultimately lead to lymphokine production, T-cell proliferation and differentiation. Furthermore, ZAP70 controls cytoskeleton modifications, adhesion and mobility of T-lymphocytes, thus ensuring correct delivery of effectors to the APC. ZAP70 is also required for TCR-CD247/CD3Z internalization and degradation through interaction with the E3 ubiquitin-protein ligase CBL and adapter proteins SLA and SLA2. Thus, ZAP70 regulates both T-cell activation switch on and switch off by modulating TCR expression at the T-cell surface.

Background References

1. Fischer A. et. al. ZAP70: a master regulator of adaptive immunity. Semin. Immunopathol. 32:107-116(2010).

2. Hu H. et. al. Otud7b facilitates T cell activation and inflammatory responses by regulating Zap70 ubiquitination. J. Exp. Med. 213:399-414(2016)

Sequence Similarity

Belongs to the protein kinase superfamily. Tyr protein kinase family. SYK/ZAP-70 subfamily.

Tissue Specificity

Expressed in T- and natural killer cells. Also present in early thymocytes and pro/pre B-cells.

Post-translational Modification

Phosphorylated on tyrosine residues upon T-cell antigen receptor (TCR) stimulation. Phosphorylation of Tyr-315 and Tyr-319 are essential for ZAP70 positive function on T-lymphocyte activation whereas Tyr-292 has a negative regulatory role. Within the C-terminal kinase domain, Tyr-492 and Tyr-493 are phosphorylated after TCR induction, Tyr-492 playing a negative regulatory role and Tyr-493 a positive. Tyr-493 is dephosphorylated by PTN22.; Ubiquitinated in response to T cell activation. Deubiquitinated by OTUD7B.

Subcellular Location

Cell membrane, cytoplasm.

UNIPROT

SwissProt: P43403 Human

SwissProt: P43404 Mouse

Entrez Gene: 301348 Rat

Synonyms