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J Biol Chem

Title:		Receptor-independent activators of heterotrimeric G-protein signaling pathways
Author(s):		Takesono A; Cismowski MJ; Ribas C; Bernard M; Chung P; Hazard S; Duzic E; Lanier SM;
Address:		"Department of Pharmacology, Medical University of South Carolina, Charleston, South Carolina 29425, USA"
Journal Title:		J Biol Chem
Year:		1999
Volume:		274
Issue:		47
Page Number:		33202 - 33205
DOI:		10.1074/jbc.274.47.33202
ISSN/ISBN:		0021-9258 (Print) 0021-9258 (Linking)
Abstract:		"Heterotrimeric G-protein signaling systems are activated via cell surface receptors possessing the seven-membrane span motif. Several observations suggest the existence of other modes of stimulus input to heterotrimeric G-proteins. As part of an overall effort to identify such proteins we developed a functional screen based upon the pheromone response pathway in Saccharomyces cerevisiae. We identified two mammalian proteins, AGS2 and AGS3 (activators of G-protein signaling), that activated the pheromone response pathway at the level of heterotrimeric G-proteins in the absence of a typical receptor. beta-galactosidase reporter assays in yeast strains expressing different Galpha subunits (Gpa1, G(s)alpha, G(i)alpha(2(Gpa1(1-41))), G(i)alpha(3(Gpa1(1-41))), Galpha(16(Gpa1(1-41)))) indicated that AGS proteins selectively activated G-protein heterotrimers. AGS3 was only active in the G(i)alpha(2) and G(i)alpha(3) genetic backgrounds, whereas AGS2 was active in each of the genetic backgrounds except Gpa1. In protein interaction studies, AGS2 selectively associated with Gbetagamma, whereas AGS3 bound Galpha and exhibited a preference for GalphaGDP versus GalphaGTPgammaS. Subsequent studies indicated that the mechanisms of G-protein activation by AGS2 and AGS3 were distinct from that of a typical G-protein-coupled receptor. AGS proteins provide unexpected mechanisms for input to heterotrimeric G-protein signaling pathways. AGS2 and AGS3 may also serve as novel binding partners for Galpha and Gbetagamma that allow the subunits to subserve functions that do not require initial heterotrimer formation"
Keywords:		"Amino Acid Sequence Animals Base Sequence DNA Primers Heterotrimeric GTP-Binding Proteins/*metabolism Molecular Sequence Data Rats Saccharomyces cerevisiae/genetics Sequence Homology, Amino Acid *Signal Transduction;"
Notes:		"MedlineTakesono, A Cismowski, M J Ribas, C Bernard, M Chung, P Hazard, S 3rd Duzic, E Lanier, S M eng R01-NS24821/NS/NINDS NIH HHS/ Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. 1999/11/24 J Biol Chem. 1999 Nov 19; 274(47):33202-5. doi: 10.1074/jbc.274.47.33202"