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 pp60c-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 pp60c-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 pp60c-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 (< or = 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.
Department of Pathology, Harvard Medical School, Boston, MA 02115, USA.
A T
AT
Young
J
J
Dahl
S F
SF
Hausdorff
P H
PH
Bauer
M J
MJ
Birnbaum
T L
TL
Benjamin
D000595:Amino Acid Sequence; D000818:Animals; D000957:Antigens, Viral, Tumor / Q000378:metabolism*; D001692:Biological Transport; D015152:Blotting, Northern; D002451:Cell Compartmentation; D002462:Cell Membrane / Q000378:metabolism; D002478:Cells, Cultured; D003847:Deoxyglucose / Q000378:metabolism; D005455:Fluorescent Antibody Technique; D005947:Glucose / Q000378:metabolism*; D051272:Glucose Transporter Type 1; D051379:Mice; D008969:Molecular Sequence Data; D009004:Monosaccharide Transport Proteins / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011120:Polyomavirus; D011485:Protein Binding; D011499:Protein Processing, Post-Translational; D016392:Proto-Oncogene Proteins pp60(c-src) / Q000378:metabolism
D000957:Antigens, Viral, Tumor; D051272:Glucose Transporter Type 1; D009004:Monosaccharide Transport Proteins; C495678:Slc2a1 protein, mouse; D003847:Deoxyglucose; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor); D016392:Proto-Oncogene Proteins pp60(c-src); D005947:Glucose