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 upt ake in target tissues, mainly by translocation to the cell surface of the intracellular insulin-regulatable glucose transporter (glucose tra nsporter type 4, GLUT4), We have developed a cell line for direct, sen sitive detection of GLUT4 on the cell surface, We have suggested that insulin-activated phosphatidylinositol (PI) 3-kinase may be involved i n 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 ov ary (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, res pectively, we obtained evidence that PI 3-kinase binding sites play a key role in the signaling pathway of PDGF-stimulated GLUT4 translocati on in the CHO cell system.