Transformation-defective mutants of polyomavirus middle T antigen associate with phosphatidylinositol 3-kinase (PI 3-kinase) but are unable to maintain wild-type levels of PI 3-kinase products in intact cells.

摘要: Abstract Middle T antigen (MT) of polyomavirus causes transformation by associating with a number cellular proteins. The association and activation two such proteins, phosphatidylinositol 3-kinase (PI 3-kinase) pp60c-src, appears to be necessary for MT. tyrosine kinase activity MT-associated pp60c-src is significantly increased when assayed in vitro, levels phosphotyrosine-containing proteins are elevated vivo. Similarly, the PI products phosphatidylinositol-3,4-bisphosphate [PI(3,4)P2] phosphatiylinositol-3,4,5-trisphosphate [PI(3,4,5)P3] constitutively MT-transformed cells. However, formation complete MT/cellular protein complex not sufficient cause transformation, since transformation-defective mutants 248m dl1015 associate all wild-type including neither mutant defective activity. Studies presented here compared (i) amount associated MT (ii) [3H]inositol incorporation into cells expressing or results show that both assays, whereas only PI(3,4,5)P2 PI(3,4)P3. These findings identify biochemical defect corroborate previous correlating In addition, they indicate product affected factors other than simply complex.