title: Platelet-derived growth factor triggers translocation of the insulin-regulatable glucose transporter (type 4) predominantly through phosphatidylinositol 3-kinase binding sites on the receptor.
abstract: Insulin is the only known hormone which rapidly stimulates glucose uptake in target tissues, mainly by translocation to the cell surface of the intracellular insulin-regulatable glucose transporter (glucose transporter type 4, GLUT4). We have developed a cell line for direct, sensitive detection of GLUT4 on the cell surface. We have suggested that insulin-activated phosphatidylinositol (PI) 3-kinase may be involved in the signaling pathway of insulin-stimulated GLUT4 translocation. We report that platelet-derived growth factor (PDGF), which stimulates PI 3-kinase activity, triggers GLUT4 translocation in Chinese hamster ovary (CHO) cells stably overexpressing the PDGF receptor and in 3T3-L1 mouse adipocytes. Using mutant PDGF receptors that cannot bind to Ras-GTPase-activating protein, phospholipase C-gamma, and PI 3-kinase, respectively, we obtained evidence that PI 3-kinase binding sites play a key role in the signaling pathway of PDGF-stimulated GLUT4 translocation in the CHO cell system.
authors.affiliation: Department of Enzyme Genetics, University of Tokushima, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Kamohara
authors.forename: H
authors.initials: H
authors.lastname: Hayashi
authors.forename: M
authors.initials: M
authors.lastname: Todaka
authors.forename: F
authors.initials: F
authors.lastname: Kanai
authors.forename: K
authors.initials: K
authors.lastname: Ishii
authors.forename: T
authors.initials: T
authors.lastname: Imanaka
authors.forename: J A
authors.initials: JA
authors.lastname: Escobedo
authors.forename: L T
authors.initials: LT
authors.lastname: Williams
authors.forename: Y
authors.initials: Y
authors.lastname: Ebina
mesh_terms: D016475:3T3 Cells; D000818:Animals; D001665:Binding Sites; D001692:Biological Transport; D016466:CHO Cells; D006224:Cricetinae; D015536:Down-Regulation; D004789:Enzyme Activation; D051275:Glucose Transporter Type 4; D007328:Insulin / Q000378:metabolism*; D051379:Mice; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D009124:Muscle Proteins; D009154:Mutation; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D010982:Platelet-Derived Growth Factor / Q000494:pharmacology*; D011493:Protein Kinase C / Q000378:metabolism; D017479:Receptors, Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism*
chemical_list: D051275:Glucose Transporter Type 4; D007328:Insulin; D009004:Monosaccharide Transport Proteins; D009124:Muscle Proteins; D010982:Platelet-Derived Growth Factor; C495693:Slc2a4 protein, mouse; D015240:Phorbol 12,13-Dibutyrate; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D017479:Receptors, Platelet-Derived Growth Factor; D011493:Protein Kinase C