title: Interaction of the human insulin receptor with the ras oncogene product p21.
abstract: Autophosphorylation of the purified human insulin receptor tyrosyl kinase was found to be inhibited by the ras oncogene product p21 in a concentration- and GDP-dependent manner. GDP-beta-S but not Gpp(NH)p could substitute for GDP in eliciting the ras-dependent inhibition. The inhibition was seen with both normal or mutant (Lys-61) p21N-ras and normal or mutant (Val-12) p21Ha-ras. Inhibition occurred at 23 degrees C but not 4 degrees C and was unaffected by the presence or absence of insulin although insulin stimulated the autophosphorylation rate of the receptor beta-subunit some 2-fold. The insulin receptor did not phosphorylate native p21Ha-ras in the presence or absence of added guanine nucleotide. After denaturation of p21Ha-ras with urea it became a substrate, but then failed to inhibit receptor autophosphorylation even in the presence of added GDP.
mesh_terms: D019204:GTP-Binding Proteins / Q000378:metabolism; D006153:Guanosine Diphosphate / Q000031:analogs & derivatives / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D016283:Proto-Oncogene Proteins p21(ras); D011972:Receptor, Insulin / Q000187:drug effects*; D011994:Recombinant Proteins
chemical_list: D007328:Insulin; D011518:Proto-Oncogene Proteins; D011994:Recombinant Proteins; D006153:Guanosine Diphosphate; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D019204:GTP-Binding Proteins; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)