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J Biol Chem, Vol. 273, Issue 25, 15445-15452, June 19, 1998
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From the The Syk family tyrosine kinases play a crucial
role in antigen receptor-mediated signal transduction, but their
regulation and cellular targets remain incompletely defined. Following
receptor engagement, phosphorylation of tyrosine residues within ZAP-70 and Syk is thought to control both kinase activity and recruitment of
modulatory factors. We report here the characterization of novel
mutants of ZAP-70 and Syk, in which conserved C-terminal tyrosine
residues have been replaced by phenylalanines (ZAP YF-C, Syk YF-C).
Both mutant kinases display a prominent gain-of-function phenotype in
Jurkat T cells, as demonstrated by lymphokine promoter activation,
tyrosine phosphorylation of potential targets in vivo, and
elevated intracellular calcium mobilization. While the presence of
p56-Lck was required for ZAP YF-C-induced signaling, Syk YF-C showed
enhanced functional activity in Lck-deficient JCaM1 Jurkat cells. Our
results implicate the C terminus of Syk family kinases as an important
regulatory region modulating T cell activation.
Laboratorium für Molekulare Biologie,
Genzentrum der Universität München, Feodor Lynen Strasse
25, D-81377 München, Germany and the § NIEHS, National
Institutes of Health, Research Triangle Park,
North Carolina 27709
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