Polyoma middle T antigen activates the Ser/Thr kinase Akt in a PI3-kinase-dependent manner.
Polyoma middle T antigen (PMT) was originally identified as the tumorigenic component of the polyomavirus genome. To investigate whether the serine/ threonine kinase Akt/PKB, which is the proto-oncogene transduced by the transforming AKT8 retrovirus, is activated by PMT, 3T3-L1 fibroblasts were stably transfected with wild type PMT. PMT expression accelerated glucose transport and increased phosphorylation of p70 S6-kinase and MAPK. PMT expression also stimulated Akt kinase activity 7 fold as compared to untreated, mock infected cells. This stimulation rivaled that obtained following insulin treatment of both mock and PMT infected cells. Akt activation and phosphorylation were eliminated in a PMT mutant incapable of interacting with PI3-kinase, but not one which does not interact with Shc, and correlated closely to the amount of PI3-kinase activity in anti-phosphotyrosine immunoprecipitates. These results indicate that the PI3-kinase pathway is requisite, but the Shc pathway is dispensable, for Akt activation. The studies further suggest that Akt may participate in PMT and PI3-kinase's regulation of cellular transformation and tumorigenesis.
Summers
S A
SA
Howard Hughes Medical Institute, University of Pennsylvania School of Medicine, Philadelphia 19104, USA.
Lipfert
L
L
Birnbaum
M J
MJ
D016475:3T3 Cells; D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics / Q000378:metabolism*; D002471:Cell Transformation, Neoplastic; D004789:Enzyme Activation; D051379:Mice; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism*; D011120:Polyomavirus / Q000235:genetics / Q000276:immunology / Q000472:pathogenicity; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt