title: Insulin receptor substrate 1 is phosphorylated by the serine kinase activity of phosphatidylinositol 3-kinase.
abstract: Insulin receptor substrate (IRS) 1, which is tyrosine phosphorylated in response to insulin, presents multiple serine/threonine phosphorylation sites. To search for a serine kinase activity towards IRS 1, immunoprecipitates from basal or stimulated 3T3-L1 adipocytes were used in an in vitro kinase assay. When IRS 1 was isolated from insulin-treated cells, serine phosphorylation of IRS 1 occurred, which we attribute to the kinase activity of the phosphatidylinositol 3-kinase (PI3-kinase). Importantly, in an in vitro reconstitution assay, an excess of the PI3-kinase subunit prevents this phosphorylation. Together, our results suggest that following insulin stimulation, PI3-kinase associates with IRS 1, allowing for its serine phosphorylation. This phosphorylation event could play a role in the modulation of insulin signalling.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale, INSERM U 145, Faculté de Médecine, Nice, France.
authors.forename: J F
authors.initials: JF
authors.lastname: Tanti
authors.forename: T
authors.initials: T
authors.lastname: Grémeaux
authors.forename: E
authors.initials: E
authors.lastname: Van Obberghen
authors.forename: Y
authors.initials: Y
authors.lastname: Le Marchand-Brustel
mesh_terms: D016475:3T3 Cells; D000818:Animals; D004789:Enzyme Activation; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000378:metabolism*; D013379:Substrate Specificity
chemical_list: D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017346:Protein Serine-Threonine Kinases; D011972:Receptor, Insulin