title: Phospholipase C-gamma is required for agonist-induced Ca2+ entry.
abstract: We report here that PLC-gamma isoforms are required for agonist-induced Ca2+ entry (ACE). Overexpressed wild-type PLC-gamma1 or a lipase-inactive mutant PLC-gamma1 each augmented ACE in PC12 cells, while a deletion mutant lacking the region containing the SH3 domain of PLC-gamma1 was ineffective. RNA interference to deplete either PLC-gamma1 or PLC-gamma2 in PC12 and A7r5 cells inhibited ACE. In DT40 B lymphocytes expressing only PLC-gamma2, overexpressed muscarinic M5 receptors (M5R) activated ACE. Using DT40 PLC-gamma2 knockout cells, M5R stimulation of ER Ca2+ store release was unaffected, but ACE was abolished. Normal ACE was restored by transient expression of PLC-gamma2 or a lipase-inactive PLC-gamma2 mutant. The results indicate a lipase-independent role of PLC-gamma in the physiological agonist-induced activation of Ca2+ entry.
authors.affiliation: Department of Neuroscience, Department of Pharmacology and Molecular Sciences, Department of Psychiatry, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
authors.forename: Randen L
authors.initials: RL
authors.lastname: Patterson
authors.forename: Damian B
authors.initials: DB
authors.lastname: van Rossum
authors.forename: Diana L
authors.initials: DL
authors.lastname: Ford
authors.forename: Kenneth J
authors.initials: KJ
authors.lastname: Hurt
authors.forename: Sun Sik
authors.initials: SS
authors.lastname: Bae
authors.forename: Pann Ghill
authors.initials: PG
authors.lastname: Suh
authors.forename: Tomohiro
authors.initials: T
authors.lastname: Kurosaki
authors.forename: Solomon H
authors.initials: SH
authors.lastname: Snyder
authors.forename: Donald L
authors.initials: DL
authors.lastname: Gill
mesh_terms: D000818:Animals; D002118:Calcium; D002384:Catalysis; D002461:Cell Line, Transformed; D006801:Humans; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism*; D016716:PC12 Cells; D051966:Phospholipase C gamma; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D051381:Rats; D010738:Type C Phospholipases / Q000235:genetics / Q000378:metabolism*
chemical_list: D007527:Isoenzymes; D012330:RNA, Double-Stranded; D034741:RNA, Small Interfering; D010738:Type C Phospholipases; D051966:Phospholipase C gamma; D002118:Calcium