Critical role of PIP5KI{gamma}87 in InsP3-mediated Ca(2+) signaling.
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.
Wang
Ying Jie
YJ
Department of Physiology, University of Texas Southwestern Medical Center at Dallas, Dallas, TX 75390, USA.
Li
Wen Hong
WH
Wang
Jing
J
Xu
Ke
K
Dong
Ping
P
Luo
Xiang
X
Yin
Helen L
HL
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
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