Premium
Fyn and Lck tyrosine kinases regulate tyrosine phosphorylation of p105 CasL , a member of the p130 Cas docking protein family, in T‐cell receptor‐mediated signalling
Author(s) -
Hiroko Kanda,
Toshihide Mimura,
Ken Hamasaki,
Kimiko Yamamoto,
Yoshio Yazaki,
Hisamaru Hirai,
Yoshihisa Nojima
Publication year - 1999
Publication title -
immunology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.297
H-Index - 133
eISSN - 1365-2567
pISSN - 0019-2805
DOI - 10.1046/j.1365-2567.1999.00753.x
Subject(s) - fyn , t cell receptor , phosphorylation , tyrosine kinase , biology , microbiology and biotechnology , cd3 , proto oncogene tyrosine protein kinase src , tyrosine phosphorylation , kinase , t cell , tyrosine protein kinase csk , tyrosine , signal transduction , sh2 domain , cd8 , biochemistry , immunology , immune system
We have previously shown that engagement of the T‐cell receptor (TCR)/CD3 complex with anti‐CD3 antibody induces tyrosine phosphorylation of p105 CasL (CasL), a member of the p130 Cas docking protein family. In the present work, we attempted to determine which protein tyrosine kinases (PTKs) regulate TCR‐mediated phosphorylation of CasL. We show here that an association between CasL and two types of Src family PTKs, Fyn and Lck, is induced by anti‐CD3 cross‐linking of human H9 T cells. In contrast, ZAP‐70, another PTK that also plays a critical role in the TCR signalling, failed to bind CasL, even after anti‐CD3 stimulation. In vitro kinase assays revealed that Fyn and Lck, but not ZAP‐70, were capable of phosphorylating CasL. Moreover, we found that CasL was constitutively hyperphosphorylated in vivo in splenocytes of MRL‐MP‐ lpr / lpr mice, in which overproduction and excessive activation of Fyn and Lck have previously been shown to occur. Constitutive in vivo binding of CasL to both kinases was also demonstrated in lpr splenocytes. These results strongly suggest that CasL is a substrate for Fyn and Lck PTKs in TCR signal transduction.