Phosphatidylinositol 3,5-bisphosphate defines a novel PI 3-kinase pathway in resting mouse fibroblasts

PtdIns(3,5)P2 is identified as the product of an agonist-independent, wortmannin-sensitive pathway in resting mouse cells. Results are presented here to indicate that PtdIns(3,5)P2 is formed by phosphorylation of PtdIns3P at the D-5 position, and they suggest that relatively constant cellular levels of PtdIns3P and PtdIns(3, 5)P2 are maintained by the concerted action of PtdIns3P 5-kinase and PtdIns(3,5)P2 5-phosphatase. These studies imply a novel mechanism for the action of PtdIns-specific phosphoinositide 3-hydroxykinases in mammalian cells.