title: Phosphatidylinositol-4-phosphate 5-kinase isozymes catalyze the synthesis of 3-phosphate-containing phosphatidylinositol signaling molecules.
abstract: Phosphatidylinositol-4-phosphate 5-kinases (PIP5Ks) utilize phosphatidylinositols containing D-3-position phosphates as substrates to form phosphatidylinositol 3,4-bisphosphate. In addition, type I PIP5Ks phosphorylate phosphatidylinositol 3, 4-bisphosphate to phosphatidylinositol 3,4,5-trisphosphate, while type II kinases have less activity toward this substrate. Remarkably, these kinases can convert phosphatidylinositol 3-phosphate to phosphatidylinositol 3,4,5-trisphosphate in a concerted reaction. Kinase activities toward the 3-position phosphoinositides are comparable with those seen with phosphatidylinositol 4-phosphate as the substrate. Therefore, the PIP5Ks can synthesize phosphatidylinositol 4,5-bisphosphate and two 3-phosphate-containing polyphosphoinositides. These unexpected activities position the PIP5Ks as potential participants in the generation of all polyphosphoinositide signaling molecules.
authors.affiliation: Department of Internal Medicine, Washington University School of Medicine, St. Louis, Missouri 63100, USA.
authors.forename: X
authors.initials: X
authors.lastname: Zhang
authors.forename: J C
authors.initials: JC
authors.lastname: Loijens
authors.forename: I V
authors.initials: IV
authors.lastname: Boronenkov
authors.forename: G J
authors.initials: GJ
authors.lastname: Parker
authors.forename: F A
authors.initials: FA
authors.lastname: Norris
authors.forename: J
authors.initials: J
authors.lastname: Chen
authors.forename: O
authors.initials: O
authors.lastname: Thum
authors.forename: G D
authors.initials: GD
authors.lastname: Prestwich
authors.forename: P W
authors.initials: PW
authors.lastname: Majerus
authors.forename: R A
authors.initials: RA
authors.lastname: Anderson
mesh_terms: D000818:Animals; D019556:COS Cells; D002384:Catalysis; D002851:Chromatography, High Pressure Liquid; D004591:Electrophoresis, Polyacrylamide Gel; D007527:Isoenzymes / Q000378:metabolism*; D007700:Kinetics; D018129:Phosphatidylinositol Phosphates / Q000378:metabolism; D010716:Phosphatidylinositols / Q000096:biosynthesis*; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000378:metabolism*; D021382:Protein Sorting Signals / Q000096:biosynthesis*
chemical_list: D007527:Isoenzymes; D018129:Phosphatidylinositol Phosphates; D010716:Phosphatidylinositols; D021382:Protein Sorting Signals; C060974:phosphatidylinositol 3,4,5-triphosphate; C060980:phosphatidylinositol 3,4-diphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase