SPECIFIC ASSOCIATION OF TYROSINE-PHOSPHORYLATED C-CBL WITH FYN TYROSINE KINASE IN T-CELLS

Fyn is a Src family protein tyrosine kinase functionally associated wi th the T-cell antigen receptor (TcR)/CD3 receptor complex. We have dem onstrated earlier that the TcR/CD3-induced activation of Fyn results i n tyrosine phosphorylation of several Fyn-associated proteins, includi ng a protein of 116 kDa. In this resort, we identify the Fyn-associate d 116-kDa phosphoprotein (p116) as c-Cbl. The identity of p116 has bee n demonstrated by its specific reactivity with anti-Cbl and similarity of phosphopeptides generated by V8 proteolysis of phospho-Cbl and p11 6. We demonstrate here that the association of Fyn and c-Cbl is direct and does not require the presence of other proteins. We also demonstr ate that Fyn is the Src family kinase that preferentially inter acts w ith c-Cbl in T cells. The fraction of c-Cbl capable of coprecipitating with Fyn is increased by TcR/CD3 ligation. This increase is likely du e to the involvement of Fyn SH2 in the interactions between Fyn and ty rosine-phosphorylated c-Cbl.