Phosphoinositide 3-Kinase as an Upstream Regulator of the Small GTP-Binding Protein Rac in the Insulin Signaling of Membrane Ruffling

• Published in: Biochemical and biophysical research communications 1995-03, Vol.208 (3), p.985-990
• Main Authors: Kotani, K., Hara, K., Yonezawa, K., Kasuga, M.
• Format: Article
• Language: English
• Subjects: Animals; Cell Membrane - physiology; Cell Membrane - ultrastructure; CHO Cells; Cricetinae; GTP-Binding Proteins - biosynthesis; GTP-Binding Proteins - isolation & purification; GTP-Binding Proteins - metabolism; Homeostasis; Humans; KB Cells; Macromolecular Substances; Mutagenesis; Phosphatidylinositol 3-Kinases; Phosphotransferases (Alcohol Group Acceptor) - biosynthesis; Phosphotransferases (Alcohol Group Acceptor) - metabolism; Pinocytosis; rac GTP-Binding Proteins; Receptor, Insulin - biosynthesis; Receptor, Insulin - metabolism; Recombinant Proteins - biosynthesis; Recombinant Proteins - metabolism; Signal Transduction; Transfection
• ISSN: 0006-291X; 1090-2104
• DOI: 10.1006/bbrc.1995.1431

Membrane ruffling and the closely linked response of fluid-phase pinocytosis were investigated in Chinese hamster ovary cells that stably overexpress the human insulin receptor and a mutant 85-kDa subunit of phosphoinositide (PI) 3-kinase (Δp85) that lacks a binding site for the catalytic 110-kDa subunit of this enzyme. Both membrane ruffling and pinocytosis induced by insulin were markedly impaired in these cells. Microinjection of Rac, a Ras-related small GTP-binding protein, induced membrane ruffling in human epidermoid carcinoma KB cells, and this effect of Rac was not blocked by coinjection of Δp85 or by exposure of cells to wortmannin, a specific Pl 3-kinase inhibitor. These results suggest that PI 3-kinase is essential not only for insulin-stimulated membrane ruffling but also for pinocytosis, and that PI 3-kinase possibly functions upstream of Rac in the signal transduction pathway.