title: Suppression of Gi alpha 2 enhances phospholipase C signalling.
abstract: G-proteins mediate transmembrane signalling from a populous group of cell-surface receptors to a smaller group of effectors that includes adenylate cyclase, various ion channels and phospholipase C. Stem cells (F9 teratocarcinoma) or rat osteosarcoma 17/2.8 cells in which Gi alpha 2 expression is abolished by antisense RNA display markedly elevated basal inositol 1,4,5-trisphosphate accumulation and a potentiated phospholipase C response to stimulatory hormones. Expression of the Q205L mutant of Gi alpha 2, which is constitutively active, was found to block persistently hormonally stimulated phospholipase C activity, implicating Gi alpha 2 as an inhibitory regulator of phospholipase C signalling. Analysis using Gi alpha 2-deficient adipocytes of transgenic mice provided further evidence for a role for Gi alpha 2 in phospholipase C regulation, demonstrating in vivo that loss of Gi alpha 2 elevates basal, and markedly potentiates hormonally stimulated, phospholipase C activity. This report demonstrates for the first time that a single G-protein, G12, can regulate two distinct signalling pathways, i.e. adenylate cyclase and phospholipase C.
authors.affiliation: Department of Molecular Pharmacology, School of Medicine, University of Stony Brook, NY 11794-8651.
authors.forename: D C
authors.initials: DC
authors.lastname: Watkins
authors.forename: C M
authors.initials: CM
authors.lastname: Moxham
authors.forename: A J
authors.initials: AJ
authors.lastname: Morris
authors.forename: C C
authors.initials: CC
authors.lastname: Malbon
mesh_terms: D017667:Adipocytes / Q000201:enzymology / Q000378:metabolism; D000818:Animals; D019204:GTP-Binding Proteins / Q000037:antagonists & inhibitors / Q000378:metabolism*; D007295:Inositol Phosphates / Q000378:metabolism; D051379:Mice; D008822:Mice, Transgenic; D015398:Signal Transduction; D014407:Tumor Cells, Cultured; D010738:Type C Phospholipases / Q000378:metabolism*
chemical_list: D007295:Inositol Phosphates; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins