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Activation of ZAP‐70 kinase activity by phosphorylation of tyrosine 493 is required for lymphocyte antigen receptor function.
Author(s) -
Chan A.C.,
Dalton M.,
Johnson R.,
Kong G.H.,
Wang T.,
Thoma R.,
Kurosaki T.
Publication year - 1995
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1002/j.1460-2075.1995.tb07247.x
Subject(s) - biology , phosphorylation , lymphocyte activation , microbiology and biotechnology , tyrosine phosphorylation , function (biology) , tyrosine kinase , antigen , t cell receptor , lymphocyte , kinase , signal transduction , biochemistry , immune system , immunology , t cell
ZAP‐70 is a protein tyrosine kinase (PTK) required for T‐cell development and T‐cell antigen receptor (TCR) function. ZAP‐70 is associated with the phosphorylated antigen receptor and undergoes tyrosine phosphorylation following receptor activation. We demonstrate here that tyrosine phosphorylation of ZAP‐70 results in an increase in its catalytic activity and that this activation is mediated by the phosphorylation of tyrosine residue 493 by the src family of PTKs. The activity of baculoviral expressed ZAP‐70 was up‐regulated 10‐fold when ZAP‐70 was co‐infected and phosphorylated by the src family PTK, lck. Mutation of Y493 alone abrogated the ability of ZAP‐70 to be activated by lck. Moreover, we demonstrate that phosphorylation of Y493 and activation of ZAP‐70 is required for antigen receptor‐mediated induction of interleukin‐2 (IL‐2) secretion in lymphocytes.