Identification of a cellular 110 000-Da protein substrate for the insulin-receptor kinase.
Addition of insulin to wheat-germ-lectin-purified glycoproteins derived from rat hepatocytes or rabbit brown adipose tissue results in the increased phosphorylation of a Mr-110 000 protein. This naturally occurring glycoprotein appears as a monomeric structure and is not part of the insulin receptor itself, since it is not immunoprecipitated by highly specific antibodies to insulin receptor. Phosphorylation of the Mr-110 000 protein and autophosphorylation of the receptor beta-subunit (Mr 95 000) are stimulated by insulin in a remarkably similar dose-dependent fasion, with half-maximal stimulation at 1 nM-insulin. Further, kinetic studies suggest that the phosphorylation of the Mr-110 000 protein occurs after autophosphorylation of the insulin-receptor kinase. In conclusion, the present identification of an endogenous substrate for the insulin-receptor kinase could suggest that some, if not all, effects of insulin may be mediated through activation of this kinase.
Sadoul
J L
JL
Peyron
J F
JF
Ballotti
R
R
Debant
A
A
Fehlmann
M
M
Van Obberghen
E
E
D000273:Adipose Tissue / Q000378:metabolism; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004591:Electrophoresis, Polyacrylamide Gel; D006023:Glycoproteins / Q000378:metabolism*; D007328:Insulin / Q000494:pharmacology; D008099:Liver / Q000166:cytology / Q000378:metabolism; D008297:Male; D008970:Molecular Weight; D010750:Phosphoproteins / Q000276:immunology / Q000302:isolation & purification; D010766:Phosphorylation; D011494:Protein Kinases / Q000378:metabolism*; D011817:Rabbits; D051381:Rats; D011919:Rats, Inbred Strains; D011972:Receptor, Insulin
D006023:Glycoproteins; D007328:Insulin; D010750:Phosphoproteins; D011494:Protein Kinases; D011972:Receptor, Insulin