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Publication : Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn).

First Author  Cooke MP Year  1991
Journal  Cell Volume  65
Issue  2 Pages  281-91
PubMed ID  2015626 Mgi Jnum  J:30985
Mgi Id  MGI:78266 Doi  10.1016/0092-8674(91)90162-r
Citation  Cooke MP, et al. (1991) Regulation of T cell receptor signaling by a src family protein-tyrosine kinase (p59fyn). Cell 65(2):281-91
abstractText  Engagement of the clonotypic antigen receptor (TCR) on T lymphocytes provokes an activation response leading to cell proliferation and lymphokine secretion. To examine the molecular basis of T cell signaling, we generated transgenic animals in which a lymphocyte-specific nonreceptor protein-tyrosine kinase p59fyn(T) is 20-fold overexpressed in developing T lineage cells. Thymocytes from these mice, analyzed using both cellular and biochemical assays, were remarkably hyperstimulable. Moreover, the responsiveness of normal thymocytes to TCR-derived signals correlated well with the extent to which p59fyn was expressed in these cells. Overexpression of a catalytically inactive form of p59fyn substantially inhibited TCR-mediated activation in otherwise normal thymocytes. These effects are unique to p59fyn; overexpression of a closely related T cell-specific tyrosine kinase, p56lck, elicits dramatically different phenotypes. Our results suggest that p59fyn is a critically important component of the TCR signal transduction apparatus.
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