Peptides representing two putative G-protein-binding motifs (GPBPl and GPBP2) derived from insulin-receptor sequences were tested for their ability to stimulate guanosine 5'-[γ-thio]triphosphate (GTP[S]; 'GTPγS') binding to a preparation containing the 41 and 67 kDa G-proteins that are associated with the insulin receptor specifically stimulated GTP[S] binding, whereas GPBPl (1319-1333) did not. Substitution of Arg-1152 with Gln in GPBP2 corresponding to a mutation site in insulin-resistant patients attenuated the stimulatory potency of GPBP2. Size-exclusion chromatography and studies with purified 67 kDa G-protein revealed that GPBP2 stimulated GTP[S] binding only to the 67 kDa G-protein. These studies provide evidence for a potential regulatory site for G-protein interaction with the insulin receptor in the tyrosine kinase domain.
