Phosphatidylinositol metabolism in cells transformed by polyomavirus middle T antigen.
Associated with the middle T antigen of polyomavirus is a novel phosphatidylinositol (PtdIns) kinase activity which phosphorylates PtdIns at the D-3 position of the inositol ring. We have undertaken an analysis of myo-[3H]inositol-containing compounds in a panel of NIH 3T3 cell lines stably transfected with transforming and nontransforming middle T antigen mutants. All cell lines from which PtdIns 3-kinase activity coprecipitated with middle T antigen exhibited modestly elevated levels of PtdIns(3)P and compounds with predicted PtdIns(3,4)P2 and PtdIns(3,4,5)P3 structures. Complex formation between middle T antigen and PtdIns 3-kinase correlated not with an increase in total inositol phosphate levels but rather with elevated levels of InsP2 and InsP4. A specific increase in the level of an InsP2 species which comigrated in high-pressure liquid chromatography analysis with Ins(3,4)P2 was observed. These results suggest that association of the polyomavirus middle T antigen with PtdIns 3-kinase activates a distinct inositol metabolic pathway.
Ulug
E T
ET
Differentiation Programme, European Molecular Biology Laboratory, Heidelberg, Federal Republic of Germany.
Hawkins
P T
PT
Hanley
M R
MR
Courtneidge
S A
SA
D000818:Animals; D000952:Antigens, Polyomavirus Transforming / Q000235:genetics*; D002472:Cell Transformation, Viral; D002478:Cells, Cultured; D002851:Chromatography, High Pressure Liquid; D007294:Inositol / Q000378:metabolism; D007295:Inositol Phosphates / Q000302:isolation & purification / Q000378:metabolism*; D051379:Mice; D009154:Mutation; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols / Q000302:isolation & purification / Q000378:metabolism*; D010766:Phosphorylation; D011120:Polyomavirus / Q000235:genetics* / Q000276:immunology; D014162:Transfection
D000952:Antigens, Polyomavirus Transforming; D007295:Inositol Phosphates; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D007294:Inositol