DIRECT ASSOCIATION BETWEEN THE RET RECEPTOR TYROSINE KINASE AND THE SRC-HOMOLOGY-2-CONTAINING ADAPTER PROTEIN GRB7

Adapter proteins containing Src homology 2 (SH2) domains link transmem brane receptor protein-tyrosine kinases to downstream signal transduci ng molecules, A family of SH2 containing adapter proteins including Gr b7 and Grb10 has been recently identified, We had previously shown tha t Grb10 associates with Ret via its SH2 domain in an activation-depend ent manner (Pandey, A., Duan, H., Di Fiore, P.P., and Dixit, V.M, (199 5) J. Biol, Chem, 270, 21461-21463), We now demonstrate that the relat ed adapter molecule Grb7 also associates with Ret in vitro and in vivo , and that the binding of the SH2 domain of Grb7 to Ret is direct, Thi s binding is depend ent upon Ret autophosphorylation since Grb7 is inc apable of binding a kinase-defective mutant of Ret, Thus two members o f the Grb family, Grb7 and Grb10, likely relay signals emanating from Ret to other, as yet, unidentified targets within the cell.