PHOSPHATIDYLINOSITOL-4-PHOSPHATE 5-KINASE ISOZYMES CATALYZE THE SYNTHESIS OF 3-PHOSPHATE-CONTAINING PHOSPHATIDYLINOSITOL SIGNALING MOLECULES

Phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks) utilize phosphatid ylinositols containing D-3-position phosphates as substrates to form p hosphatidylinositol 3,4-bisphosphate, In addition, type I PIP5Ks phosp horylate phosphatidylinositol a,4-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate, while type IT kinases have less activity toward this substrate. Remarkably, these kinases can convert phosphatidylinos itol 3-phosphate to phosphatidylinositol 3,4,5-trisphosphate in a conc erted reaction, Kinase activities toward the 3-position phosphoinositi des are comparable with those seen with phosphatidylinositol 4-phospha te as the substrate. Therefore, the PIP5Ks can synthesize phosphatidyl -inositol 4,5-bisphosphate and two 3-phosphate-containing polyphosphoi nositides. These unexpected activities position the PIP5Ks as potentia l participants in the generation of all polyphosphoinositide signaling molecules.