PHOSPHATIDYLINOSITOL 3,5-BISPHOSPHATE DEFINES A NOVEL PI 3-KINASE PATHWAY IN RESTING MOUSE FIBROBLASTS

PtdIns(3,5)P-2 is identified as the product of an agonist-independent, wortmannin-sensitive pathway in resting mouse cells. Results are pres ented here to indicate that PtdIns(3,5)P-2 is formed by phosphorylatio n of PtdIns3P at the D-5 position, and they suggest that relatively co nstant cellular levels of PtdIns3P and PtdIns(3,5)P-2 are maintained b y the concerted action of PtdIns3P 5-kinase and PtdIns(3,5)P-2 5-phosp hatase. These studies imply a novel mechanism for the action of PtdIns -specific phosphoinositide 3-hydroxykinases in mammalian cells.