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An absolute requirement for Fyn in T cell receptor‐induced caspase activation and apoptosis
Author(s) -
Ricci Jean-Ehrland,
Lang Valerie,
Luciano Fréderic,
Belhacene Nathalie,
Giordanengo Valerie,
Michel Frédérique,
Bismuth Georges,
Auberger Patrick
Publication year - 2001
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.00-0665fje
Subject(s) - fyn , apoptosis , microbiology and biotechnology , chemistry , receptor , cancer research , biology , biochemistry , proto oncogene tyrosine protein kinase src
The mechanisms by which caspases are stimulated following T cell receptor engagement are presently unknown. We show here that TCR cross‐linking induces caspase activation, annexin V binding, loss of cell viability, Fyn cleavage, and apoptosis in a T cell hybridoma. All these events are increased in T cells overexpressing wild‐type Fyn and are inhibited in cells expressing a kinase dead mutant or a soluble form of Fyn. Moreover, DNA fragmentation mediated by various proapoptotic stimuli and anti‐CD3‐induced caspase activation and DNA fragmentation are reduced significantly in mouse embryo fibroblasts and thymocytes from Fyn knockout mice respectively. These results indicate that an active and membrane‐anchored Fyn is required for T cell receptor‐induced caspase activation and apoptosis in T lymphocytes and point out a specific role of Fyn in caspase activation and apoptosis in T cells.