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Zap-70

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Zap-70

Zeta-chain (TCR) associated protein kinase 70kDa
PDB rendering based on 1m61.
Available structures
PDB Ortholog search: RCSB
Identifiers
2.7.10.2
RNA expression pattern

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

Clinical significance

ZAP-70 in B cells is used as a prognostic marker in identifying different forms of 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.[1]

In systemic lupus erythematosis, the Zap-70 receptor pathway is missing and Syk takes its place.[2]

ZAP70 deficiency results in a form of immune deficiency.

Function

T lymphocytes are activated by engagement of the T cell receptor with processed antigen fragments presented by professional antigen presenting cells (e.g. macrophages, dendritic cells and B cells). Upon this activation, the tyrosine kinase Lck becomes activated and phosphorylates the intracellular portions of the CD3 complex (called ITAMs). The most important member of the CD3 family is CD3-zeta, to which ZAP-70 binds (hence the abbreviation). The tandem SH2-domains of ZAP-70 are engaged by the doubly phosphorylated ITAMs of CD3-zeta, which positions ZAP-70 to phosphorylate the transmembrane protein linker of activated T cells (LAT). Phosphorylated LAT, in turn, serves as a docking site to which a number of signaling proteins bind. 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 cytokines.

Interactions

ZAP-70 has been shown to interact with Lck,[3][4] FYN,[5] SHB,[6] LAT,[7][8] Cbl gene,[9][10] Drebrin-like[11] and SHC1.[12]

See also

Further reading

References

External links

  • GeneReviews/NIH/NCBI/UW entry on ZAP70-Related Severe Combined Immunodeficiency
  • Medical Subject Headings (MeSH)

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