title: GTP loading of farnesylated p21Ras by insulin at the plasma membrane.
abstract: Insulin promotes the phosphorylation and activation of farnesyltransferase (FTase) in a time- and a dose-dependent manner. Increased FTase activity results in a larger pool of farnesylated p21Ras and allows for enhanced GTP loading. Insulin significantly increases the pool of farnesylated p21Ras from 20-25% in quiescent 3T3-L1 fibroblasts to approximately 70%, most of which is targeted to the plasma membrane. Furthermore, insulin promotes GTP loading of plasma membrane and not cytosolic p21Ras. The half-life of plasma membrane-associated farnesylated p21Ras is approximately 6 hours, and is identical in control and insulin-treated cells. We have also observed a direct correlation between the amounts of farnesylated p21Ras at the plasma membrane and the magnitude of insulin-induced GTP loading of p21Ras.
authors.affiliation: Medical Research Service, Veterans Affairs Medical Center, Denver, Colorado, USA.
authors.forename: M
authors.initials: M
authors.lastname: Goalstone
authors.forename: J W
authors.initials: JW
authors.lastname: Leitner
authors.forename: B
authors.initials: B
authors.lastname: Draznin
mesh_terms: D016475:3T3 Cells; D019883:Alkyl and Aryl Transferases / Q000378:metabolism; D000818:Animals; D002462:Cell Membrane / Q000187:drug effects / Q000378:metabolism; D051231:Farnesyltranstransferase; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism*; D006207:Half-Life; D007328:Insulin / Q000494:pharmacology*; D051379:Mice; D017368:Protein Prenylation; D016283:Proto-Oncogene Proteins p21(ras) / Q000378:metabolism*; D051381:Rats
chemical_list: D007328:Insulin; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D019883:Alkyl and Aryl Transferases; D051231:Farnesyltranstransferase; D016283:Proto-Oncogene Proteins p21(ras)