title: Insulin stimulation of gene expression mediated by p21ras activation.
abstract: In fibroblasts, insulin is a weak mitogen and does not induce expression of c-fos, c-jun or p33. However, increasing the expression levels of either normal p21Hras or the insulin receptor, but not mutant p21Hras, enables insulin to induce the expression of these genes. In cells expressing elevated levels of insulin receptor, this process involves a rapid increase in p21rasGTP levels (from 20% to 70% GTP as a percentage of total guanine nucleotides). No increase in p21rasGTP levels was observed after PDGF and EGF stimulation of cells expressing high levels of the cognate receptor, stressing the specificity of the insulin-induced increase. We conclude that in fibroblasts, p21ras is an intermediate of the insulin signal transduction pathway involved in the regulation of gene expression and mitogenicity.
authors.affiliation: Laboratory for Molecular Carcinogenesis, Sylvius Laboratory, Leiden, The Netherlands.
authors.forename: B M
authors.initials: BM
authors.lastname: Burgering
authors.forename: R H
authors.initials: RH
authors.lastname: Medema
authors.forename: J A
authors.initials: JA
authors.lastname: Maassen
authors.forename: M L
authors.initials: ML
authors.lastname: van de Wetering
authors.forename: A J
authors.initials: AJ
authors.lastname: van der Eb
authors.forename: F
authors.initials: F
authors.lastname: McCormick
authors.forename: J L
authors.initials: JL
authors.lastname: Bos
mesh_terms: D005347:Fibroblasts / Q000378:metabolism*; D005786:Gene Expression Regulation / Q000187:drug effects*; D006153:Guanosine Diphosphate / Q000378:metabolism; D006160:Guanosine Triphosphate / Q000378:metabolism; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D009154:Mutation; D016283:Proto-Oncogene Proteins p21(ras) / Q000235:genetics* / Q000378:metabolism; D011972:Receptor, Insulin / Q000187:drug effects / Q000235:genetics; D015398:Signal Transduction / Q000235:genetics
chemical_list: D007328:Insulin; D006153:Guanosine Diphosphate; D006160:Guanosine Triphosphate; D011972:Receptor, Insulin; C501009:HRAS protein, human; D016283:Proto-Oncogene Proteins p21(ras)