Regulation of cardiac insulin receptor function by guanosine nucleotides

[摘要]

The present study examined the effect of [³⁵S]GTP on the function of insulin receptors partially purified from adult rat cardiomyocytes by WGA chromatography. [³⁵S]GTP 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 [³⁵S]GTP was specific, dose-dependent, and due to an increase in the V _max of the kinase. In the presence of ATP or AMP-PNP, insulin significantly enhanced the binding of [³⁵S]GTP 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.

[学科分类] 生物化学/生物物理

[关键词] Isolated cardiac myocyte;Insulin receptor;Guanosine nucleotide binding protein;Tyrosine kinase;GTP;guanosine 5′-O-(3-thiotriphosphate);GDP;guanosine 5′-O-(2-thiodiphosphate);SDS-PAGE;sodium dodecyl sulfate-polyacrylamide gel electrophoresis;HEPES;4-(2-hydroxyethyl)-1-piperazineethanesulfonic acid;WGA;wheat germ agglutinin;AMP-PNP;adenyl-5′-yl imidodiphosphate