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The structure, regulation, and function of ZAP‐70
Author(s) -
AuYeung Byron B.,
Deindl Sebastian,
Hsu LihYun,
Palacios Emil H.,
Levin Susan E.,
Kuriyan John,
Weiss Arthur
Publication year - 2009
Publication title -
immunological reviews
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.839
H-Index - 223
eISSN - 1600-065X
pISSN - 0105-2896
DOI - 10.1111/j.1600-065x.2008.00753.x
Subject(s) - syk , t cell receptor , biology , signal transduction , tyrosine kinase , t cell , microbiology and biotechnology , autoimmunity , immunology , cancer research , immune system
Summary: The tyrosine ZAP‐70 (ζ‐associated protein of 70 kDa) kinase plays a critical role in activating many downstream signal transduction pathways in T cells following T‐cell receptor (TCR) engagement. The importance of ZAP‐70 is evidenced by the severe combined immunodeficiency that occurs in ZAP‐70‐deficient mice and humans. In this review, we describe recent analyses of the ZAP‐70 crystal structure, revealing a complex regulatory mechanism of ZAP‐70 activity, the differential requirements for ZAP‐70 and spleen tyrosine kinase (SyK) in early T‐cell development, as well as the role of ZAP‐70 in chronic lymphocytic leukemia and autoimmunity. Thus, the critical importance of ZAP‐70 in TCR signaling and its predominantly T‐cell‐restricted expression pattern make ZAP‐70 an attractive drug target for the inhibition of pathological T‐cell responses in disease.