title: Critical role of PIP5KI{gamma}87 in InsP3-mediated Ca(2+) signaling.
abstract: Phosphatidylinositol 4,5-bisphosphate (PIP(2)) is the obligatory precursor of inositol 1,4,5-trisphosphate (InsP(3) or IP(3)) and is therefore critical to intracellular Ca(2+) signaling. Using RNA interference (RNAi), we identified the short splice variant of type I phosphatidylinositol 4-phosphate 5-kinase gamma (PIP5KIgamma87) as the major contributor of the PIP(2) pool that supports G protein-coupled receptor (GPCR)-mediated IP(3) generation. PIP5KIgamma87 RNAi decreases the histamine-induced IP(3) response and Ca(2+) flux by 70%. Strikingly, RNAi of other PIP5KI isoforms has minimal effect, even though some of these isoforms account for a larger percent of total PIP(2) mass and have previously been implicated in receptor mediated endocytosis or focal adhesion formation. Therefore, PIP5KIgamma87's PIP(2) pool that supports GPCR-mediated Ca(2+) signaling is functionally compartmentalized from those generated by the other PIP5KIs.
authors.affiliation: Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
authors.forename: Ying Jie
authors.initials: YJ
authors.lastname: Wang
authors.forename: Wen Hong
authors.initials: WH
authors.lastname: Li
authors.forename: Jing
authors.initials: J
authors.lastname: Wang
authors.forename: Ke
authors.initials: K
authors.lastname: Xu
authors.forename: Ping
authors.initials: P
authors.lastname: Dong
authors.forename: Xiang
authors.initials: X
authors.lastname: Luo
authors.forename: Helen L
authors.initials: HL
authors.lastname: Yin
mesh_terms: D020013:Calcium Signaling / Q000502:physiology*; D006367:HeLa Cells; D006632:Histamine / Q000502:physiology; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000502:physiology*; D007527:Isoenzymes / Q000235:genetics / Q000502:physiology*; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000378:metabolism / Q000502:physiology; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000235:genetics / Q000502:physiology*; D034622:RNA Interference / Q000502:physiology; D034741:RNA, Small Interfering / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology
chemical_list: D007527:Isoenzymes; D019269:Phosphatidylinositol 4,5-Diphosphate; D034741:RNA, Small Interfering; D043562:Receptors, G-Protein-Coupled; D006632:Histamine; D015544:Inositol 1,4,5-Trisphosphate; D017853:Phosphotransferases (Alcohol Group Acceptor); C020077:1-phosphatidylinositol-4-phosphate 5-kinase