ZAP70
ZAP70 (zeta chain of T cell receptor associated protein kinase 70, also written ZAP-70) is a cytoplasmic tyrosine kinase that acts in the first steps of T-cell receptor signalling. It is essential for thymocyte development and for the regulation of the adaptive immune response. Browse Assay Genie's current range of ZAP70 research reagents below, or read on for the biology behind the target.
ZAP70 is a tyrosine kinase with an essential role in regulating the adaptive immune response. When antigen presenting cells activate the T-cell receptor (TCR), a series of phosphorylations recruits ZAP70 to the phosphorylated TCR components CD3E and CD247/CD3Z through their ITAM motifs at the plasma membrane. This recruitment localises ZAP70 to the stimulated TCR and relieves its autoinhibited conformation. The active conformation is further stabilised by phosphorylation by LCK. ZAP70 then phosphorylates at least two essential adapter proteins, LAT and LCP2, so that many signalling molecules are recruited. The outcome is lymphokine production, T-cell proliferation and differentiation.
ZAP70 also controls cytoskeletal changes, adhesion and motility in T-lymphocytes, which helps deliver effectors correctly to the antigen presenting cell. It is required for internalisation and degradation of TCR-CD247/CD3Z through interaction with the E3 ubiquitin-protein ligase CBL and the adapter proteins SLA and SLA2. ZAP70 therefore regulates both the switch-on and switch-off of T-cell activation by modulating TCR levels at the cell surface. Before positive selection, while thymocytes are still CD4/CD8 double negative, it promotes their survival and cell-cycle progression. ZAP70-dependent signalling may also contribute to the formation and activation of primary B-cells through the B-cell receptor.
The ZAP70 gene encodes a protein of the Tyr protein kinase family, SYK/ZAP-70 subfamily, and HGNC places it among SH2 domain containing proteins and Syk family tyrosine kinases. It is phosphorylated on tyrosine residues after TCR stimulation and works with the Src family kinases Lck and Fyn. Mutations in the gene cause a selective T-cell defect, a severe combined immunodeficiency characterised by absence of CD8-positive T-cells. Two transcript variants encoding different isoforms have been reported. Previous symbols and aliases include SRK and STD.
ZAP70 is recruited to phosphorylated CD3E and CD247/CD3Z and phosphorylates LAT and LCP2, making it a central node in TCR signal transduction.
ZAP70 is essential for thymocyte development, supporting survival and cell-cycle progression of double negative thymocytes before positive selection.
Mutations in ZAP70 cause a severe combined immunodeficiency with selective absence of CD8-positive T-cells, linking the kinase to inherited T-cell defects.
Through CBL, SLA and SLA2, ZAP70 regulates TCR internalisation and degradation, so it shapes both activation and termination of T-cell responses.
ZAP70 is a tyrosine kinase that transmits signals from the activated T-cell receptor. After recruitment to phosphorylated CD3E and CD247/CD3Z, it phosphorylates LAT and LCP2, driving T-cell proliferation, differentiation and cytokine production. It also supports thymocyte development and contributes to B-cell activation.
The protein is also called ZAP-70 or tyrosine-protein kinase ZAP-70, and the gene has the aliases STD and SRK, the latter being a previous symbol. NCBI Gene reports two transcript variants that encode different isoforms of the ZAP70 protein.
Yes. Mutations in the ZAP70 gene cause a selective T-cell defect, a severe combined immunodeficiency with absent CD8-positive T-cells. The mouse ortholog is Zap70; check the datasheet of any product for its validated reactivity.
Syk family kinases, TCR signalling components and adapter proteins that act alongside ZAP70 in lymphocyte activation.
Gene and protein annotations from HGNC, NCBI Gene and UniProt P43403; product specifications from Assay Genie datasheets.