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 tumori genic component of the polyomavirus genome. To investigate whether the serine/ threonine kinase Akt/PKB, which is the proto-oncogene transdu ced by the transforming AKT8 retrovirus, is activated by PMT, 3T3-L1 f ibroblasts 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 r ivaled that obtained following insulin treatment of both mock and PMT infected cells. Akt activations and phosphorylation were eliminated in a PMT mutant incapable of interacting with PI3-kinase, but not one wh ich does not interact with Shc, and correlated closely to the amount o f PI3-kinase activity in anti-phosphotyrosine immumnoprecipitates. The se results indicate that the PI3-kinase pathway is requisite, hut the Shc pathway is dispensable, for Akt activation. The studies further su ggest that Akt may participate in PMT and PI3-kinase's regulation of c ellular transformation and tumorigenesis. (C) 1998 Academic Press.