Regulation of cardiac insulin receptor function by guanosine nucleotides.
The present study examined the effect of GTP-gamma-S on the function of insulin receptors partially purified from adult rat cardiomyocytes by WGA chromatography. GTP-gamma-S increased receptor autophosphorylation about two times and fully mimicked the stimulatory action of insulin on poly(Glu:Tyr) phosphorylation with no additional effect of the hormone. The effect of GTP-gamma-S was specific, dose-dependent, and due to an increase in the Vmax of the kinase. In the presence of ATP or AMP-PNP, insulin significantly enhanced the binding of [35S]GTP-gamma-S to the partially purified insulin receptor. The findings suggest coupling of the insulin receptor to a G-protein which may be involved in the regulation of tyrosine kinase activity.
Russ
M
M
Laboratory of Molecular Cardiology, Diabetes Research Institute, Düsseldorf, Germany.
Reinauer
H
H
Eckel
J
J
D000818:Animals; D019204:GTP-Binding Proteins / Q000502:physiology*; D006150:Guanine Nucleotides / Q000502:physiology*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000494:pharmacology; D007328:Insulin / Q000494:pharmacology; D008297:Male; D009206:Myocardium / Q000378:metabolism*; D010766:Phosphorylation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D011972:Receptor, Insulin / Q000187:drug effects / Q000378:metabolism*
D006150:Guanine Nucleotides; D007328:Insulin; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D019204:GTP-Binding Proteins