Platelet-derived growth factor triggers translocation of the insulin-regulatable glucose transporter (type 4) predominantly through phosphatidylinositol 3-kinase binding sites on the receptor.
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.
Kamohara
S
S
Department of Enzyme Genetics, University of Tokushima, Japan.
Hayashi
H
H
Todaka
M
M
Kanai
F
F
Ishii
K
K
Imanaka
T
T
Escobedo
J A
JA
Williams
L T
LT
Ebina
Y
Y
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*
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