ZAP70

ZAP-70 (Zeta-chain-associated protein kinase 70) is a protein normally expressed near the surface membrane of is_associated_with::T cells and is_associated_with::natural killer cells. It is part of the is_associated_with::T cell receptor, and plays a critical role in T-cell signaling. Its molecular weight is 70 is_associated_with::kDa, and it is a member of the protein-is_associated_with::tyrosine kinase family.

Clinical significance
ZAP-70 in is_associated_with::B cells is used as a prognostic marker in identifying different forms of is_associated_with::chronic lymphocytic leukemia (CLL). DNA analysis has distinguished two major types of CLL, with different survival times. CLL that is positive for the marker ZAP-70 has an average survival of 8 years. CLL that is negative for ZAP-70 has an average survival of more than 25 years. Many patients, especially older ones, with slowly progressing disease can be reassured and may not need any treatment in their lifetimes.

In is_associated_with::systemic lupus erythematosus, the Zap-70 receptor pathway is missing and is_associated_with::Syk takes its place.

is_associated_with::ZAP70 deficiency results in a form of is_associated_with::immune deficiency.

Function
T lymphocytes are activated by engagement of the T cell receptor with processed antigen fragments presented by professional antigen presenting cells (i.e. macrophages, dendritic cells and B cells) via the MHC complex. Upon this activation, the TCR co-receptor CD4 or CD8 binds to the MHC complex, activating the co-receptor associated tyrosine kinase is_associated_with::Lck. Lck phosphorylates the intracellular portions of the CD3 complex (called ITAMs), creating a docking site for ZAP-70. The most important member of the CD3 family is is_associated_with::CD3-zeta, to which ZAP-70 binds (hence the abbreviation). The tandem is_associated_with::SH2-domains of ZAP-70 are engaged by the doubly phosphorylated ITAMs of CD3-zeta, which positions ZAP-70 to phosphorylate the transmembrane protein is_associated_with::linker of activated T cells (LAT). Phosphorylated LAT, in turn, serves as a docking site to which a number of signaling proteins bind including SLP-76. The final outcome of T cell activation is the transcription of several gene products which allow the T cells to differentiate, proliferate and secrete a number of is_associated_with::cytokines.

Interactions
ZAP-70 has been shown to interact with is_associated_with::Lck, is_associated_with::FYN, SHB, LAT,  is_associated_with::Cbl gene,  is_associated_with::Drebrin-like and is_associated_with::SHC1.