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Interaction of the human insulin receptor with the ras oncogene product p21
Author(s) -
O'Brien Richard M.,
Siddle Kenneth,
Houslay Miles D.,
Hall Alan
Publication year - 1987
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/0014-5793(87)80673-7
Subject(s) - autophosphorylation , insulin receptor , insulin , insulin receptor substrate , mutant , receptor , insulin like growth factor 1 receptor , protein subunit , chemistry , biochemistry , biology , phosphorylation , microbiology and biotechnology , endocrinology , protein kinase a , growth factor , insulin resistance , gene
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‐β‐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) p21 N‐ras and normal or mutant (Val‐12) p21 Ha‐ras . Inhibition occurred at 23°C but not 4°C and was unaffected by the presence or absence of insulin although insulin stimulated the autophosphorylation rate of the receptor β‐subunit some 2‐fold. The insulin receptor did not phosphorylate native p21 Ha‐ras in the presence or absence of added guanine nucleotide. After denaturation of p21 Ha‐ras with urea it became a substrate, but then failed to inhibit receptor autophosphorylation even in the presence of added GDP.