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Activation of Src‐family tyrosine kinases during Fas‐induced apoptosis
Author(s) -
Schlottmann Klaus E.,
Gulbins Erich,
Lau Sey M.,
Coggeshall K. Mark
Publication year - 1996
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1002/jlb.60.4.546
Subject(s) - jurkat cells , fyn , tyrosine kinase , biology , tyrosine phosphorylation , tyrosine protein kinase csk , microbiology and biotechnology , proto oncogene tyrosine protein kinase src , apoptosis , fas receptor , receptor tyrosine kinase , fas ligand , kinase , signal transduction , tyrosine , programmed cell death , t cell , cancer research , sh3 domain , biochemistry , immunology , immune system
Abstract Stimulation of several human and murine hematopoietically derived cell lines with anti‐Fas antibodies induced increased tyrosine phosphorylation of a panel of proteins observed in whole‐cell lysates. In the human T cell line Jurkat, the activity of a 56‐kDa tyrosine kinase was likewise activated by anti‐Fas antibodies. Immunoprecipitation studies of anti‐Fas‐stimulated human Jurkat and murine 2B4.11 T cells revealed activation of the Src‐family tyrosine kinases Lck and Fyn. Fas receptor‐induced tyrosine phosphorylation of p120 c‐cbl proto‐oncogene product was observed in Jurkat T cells. Pharmacological experiments demonstrated that pretreatment of Jurkat cells with tyrphostins inhibited Fas‐induced apoptosis; likewise, Lck activity was inhibited by tyrphostins in a dose‐dependent fashion. Finally, Lck derived from unstimulated Jurkat T cells formed stable complexes with the intracellular domain of the Fas receptor. These data are consistent with the notion that expression and activation of members of the Src‐family kinases is required for Fas‐induced cell death in T lymphocytes and consistent with recent findings demonstrating decreased Fas‐mediated thymocytic death in Fyn‐knockout mice. J. Leukoc. Biol . 60: 546–554; 1996.