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Eukaryot Cell

Title:		Genome-scale analysis reveals Sst2 as the principal regulator of mating pheromone signaling in the yeast Saccharomyces cerevisiae
Author(s):		Chasse SA; Flanary P; Parnell SC; Hao N; Cha JY; Siderovski DP; Dohlman HG;
Address:		"Department of Biochemistry and Biophysics, University of North Carolina, Chapel Hill, NC 27599-7260, USA"
Journal Title:		Eukaryot Cell
Year:		2006
Volume:		5
Issue:		2
Page Number:		330 - 346
DOI:		10.1128/EC.5.2.330-346.2006
ISSN/ISBN:		1535-9778 (Print) 1535-9786 (Electronic) 1535-9786 (Linking)
Abstract:		"A common property of G protein-coupled receptors is that they become less responsive with prolonged stimulation. Regulators of G protein signaling (RGS proteins) are well known to accelerate G protein GTPase activity and do so by stabilizing the transition state conformation of the G protein alpha subunit. In the yeast Saccharomyces cerevisiae there are four RGS-homologous proteins (Sst2, Rgs2, Rax1, and Mdm1) and two Galpha proteins (Gpa1 and Gpa2). We show that Sst2 is the only RGS protein that binds selectively to the transition state conformation of Gpa1. The other RGS proteins also bind Gpa1 and modulate pheromone signaling, but to a lesser extent and in a manner clearly distinct from Sst2. To identify other candidate pathway regulators, we compared pheromone responses in 4,349 gene deletion mutants representing nearly all nonessential genes in yeast. A number of mutants produced an increase (sst2, bar1, asc1, and ygl024w) or decrease (cla4) in pheromone sensitivity or resulted in pheromone-independent signaling (sst2, pbs2, gas1, and ygl024w). These findings suggest that Sst2 is the principal regulator of Gpa1-mediated signaling in vivo but that other proteins also contribute in distinct ways to pathway regulation"
Keywords:		"Amino Acid Sequence GTP-Binding Protein alpha Subunits/metabolism GTP-Binding Protein alpha Subunits, Gq-G11 GTPase-Activating Proteins/chemistry/*genetics/*metabolism Gene Deletion Gene Expression Regulation, Fungal Genome, Fungal/*genetics Genomics Mati;"
Notes:		"MedlineChasse, Scott A Flanary, Paul Parnell, Stephen C Hao, Nan Cha, Jiyoung Y Siderovski, David P Dohlman, Henrik G eng P01 GM065533/GM/NIGMS NIH HHS/ P01-GM65533/GM/NIGMS NIH HHS/ Research Support, N.I.H., Extramural Research Support, Non-U.S. Gov't 2006/02/10 Eukaryot Cell. 2006 Feb; 5(2):330-46. doi: 10.1128/EC.5.2.330-346.2006"