Expression of a prenylation-deficient Rab4 inhibits the GLUT4 translocation induced by active phosphatidylinositol 3-kinase and protein kinase B

The small GTPase Rab4 has been shown to participate in the subcellular dist ribution of GLUT4 under both basal and insulin-stimulated conditions in adi pocytes. In the present work. we have characterized the effect of Rab4 Delt a CT, a prenylation-deficient and thus cytosolic form of Rab4, in this proc ess. We show that the expression of Rab4 Delta CT in freshly isolated adipo cytes inhibits insulin-induced GLUT4 translocation, but only when this prot ein is in its GTP-bound active form. Further, it not only blocks the effect of insulin, but also that of a hyperosmotic shock, but does not interfere with the effect of zinc ions on GLUT4 translocation. Rab4 Delta CT was then shown to prevent GLUT4 translocation induced by the expression of an activ e form of phosphatidylinositol 3-kinase or of protein kinase B, without alt ering the activities of the enzymes. Our results are consistent with a role of Rab4 Delta CT acting as a dominant negative protein towards Rab4, possi bly by binding to Rab4 effectors.