CATALYTIC ACTIVITY OF THE MOUSE GUANINE-NUCLEOTIDE EXCHANGER MSOS IS ACTIVATED BY FYN TYROSINE PROTEIN-KINASE AND THE T-CELL ANTIGEN RECEPTOR IN T-CELLS

mSOS, a guanine nucleotide exchange factor, is a positive regulator of Ras, Fyn tyrosine protein kinase is a potential mediator in T-cell an tigen receptor signal transduction in subsets of T cells, We investiga ted the functional and physical interaction between mSOS and Fyn in T- cell hybridoma cells, Stimulation of the T-cell antigen receptor induc ed the activation of guanine nucleotide exchange activity in mSOS immu noprecipitates. Overexpression of Fyn mutants with an activated kinase mutation and with a Src homology 2 deletion mutation resulted in a st imulation and suppression of the mSOS activity, respectively, The comp lex formations of Fyn-Shc, Shc-Grb2, and Grb2-mSOS were detected in th e activated Fyn-transformed cells, whereas the SH2 deletion mutant of Fyn failed to form a complex with mSOS. Moreover, tyrosine phosphoryla tion of She was induced by the overexpression of the activated Fyn. Th ese findings support the idea that Fyn activates the activity of mSOS bound to Grb2 through tyrosine phosphorylation of She. Unlike the curr ent prevailing model, Fyn-induced activation of Ras might involve the stimulation of the catalytic guanine nucleotide exchange activity of m SOS.