PHOSPHATIDYLINOSITOL 3-KINASE BINDING TO POLYOMA-VIRUS MIDDLE TUMOR-ANTIGEN MEDIATES ELEVATION OF GLUCOSE-TRANSPORT BY INCREASING TRANSLOCATION OF THE GLUT1 TRANSPORTER

Elevation in the rate of glucose transport in polyoma virus-infected mouse fibroblasts was dependent upon phosphatidylinositol 3-kinase (PI 3-kinase; EC 2.7.1.137) binding to complexes of middle tumor antigen (middle T) and pp60(c-src). Wild-type polyoma virus infection led to a 3-fold increase in the rate of 2-deoxyglucose (2DG) uptake, whereas a weakly transforming polyoma virus mutant that encodes a middle T capable of activating pp60(c-src) but unable to promote binding of PI 3-kinase induced little or no change in the rate of 2DG transport, Another transformation-defective mutant encoding a middle T that retains functional binding of both pp60(c-src) and PI 3-kinase but is incapable of binding Shc (a protein involved in activation of Ras) induced 2DG transport to wild-type levels, Wortmannin (less than or equal to 100 nM), a known inhibitor of PI 3-kinase, blocked elevation of glucose transport in wild-type virus-infected cells, In contrast to serum stimulation, which led to increased levels of glucose transporter 1 (GLUT1) RNA and protein, wild-type virus infection induced no significant change in levels of either GLUT1 RNA or protein. Nevertheless, virus-infected cells did show increases in GLUT1 protein in plasma membranes, These results point to a posttranslational mechanism in the elevation of glucose transport by polyoma virus middle T involving activation of PI 3-kinase and translocation of GLUT1.