Suppression of Gi alpha 2 enhances phospholipase C signalling.
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.
Watkins
D C
DC
Department of Molecular Pharmacology, School of Medicine, University of Stony Brook, NY 11794-8651.
Moxham
C M
CM
Morris
A J
AJ
Malbon
C C
CC
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*
D007295:Inositol Phosphates; D010738:Type C Phospholipases; D019204:GTP-Binding Proteins