Attenuation of Gi- and Gq-mediated signaling by expression of RGS4 or GAIP in mammalian cells.
Protein regulators of G protein signaling (RGS proteins) were discovered as negative regulators of heterotrimeric G protein-mediated signal transduction in yeast and worms. Experiments with purified recombinant proteins in vitro have established that RGS proteins accelerate the GTPase activity of certain G protein alpha subunits (the reaction responsible for their deactivation); they can also act as effector antagonists. We demonstrate herein that either of two such RGS proteins, RGS4 or GAIP, attenuated signal transduction mediated by endogenous receptors, G proteins, and effectors when stably expressed as tagged proteins in transfected mammalian cells. The pattern of selectivity observed in vivo was similar to that seen in vitro. RGS4 and GAIP both attenuated Gi-mediated inhibition of cAMP synthesis. RGS4 was more effective than GAIP in blocking Gq-mediated activation of phospholipase Cbeta.
Huang
C
C
Department of Pharmacology, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, TX 75235, USA.
Hepler
J R
JR
Gilman
A G
AG
Mumby
S M
SM
D000818:Animals; D001483:Base Sequence; D001920:Bradykinin / Q000494:pharmacology; D002460:Cell Line; D002999:Clone Cells; D000242:Cyclic AMP / Q000378:metabolism*; D017931:DNA Primers; D019204:GTP-Binding Proteins / Q000378:metabolism*; D006801:Humans; D015544:Inositol 1,4,5-Trisphosphate / Q000378:metabolism; D007545:Isoproterenol / Q000494:pharmacology; D007700:Kinetics; D008322:Mammals; D008969:Molecular Sequence Data; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins / Q000096:biosynthesis / Q000378:metabolism*; D016133:Polymerase Chain Reaction; D014176:Protein Biosynthesis; D011506:Proteins / Q000378:metabolism*; D020710:RGS Proteins; D011993:Recombinant Fusion Proteins / Q000096:biosynthesis / Q000378:metabolism; D016324:Sequence Tagged Sites; D015398:Signal Transduction; D014162:Transfection; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D017931:DNA Primers; D009838:Oligodeoxyribonucleotides; D010750:Phosphoproteins; D011506:Proteins; D020710:RGS Proteins; D011993:Recombinant Fusion Proteins; D010566:Virulence Factors, Bordetella; C097187:regulator of G-protein signalling 19; C098799:RGS4 protein; D015544:Inositol 1,4,5-Trisphosphate; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; D007545:Isoproterenol; D001920:Bradykinin