Genome-scale analysis reveals Sst2 as the principal regulator of mating pheromone signaling in the yeast Saccharomyces cerevisiae

Scott A. Chasse, Paul Flanary, Stephen C. Parnell, Nan Hao, Jiyoung Cha, David P. Siderovski, Henrik G. Dohlman

Research output: Contribution to journalArticle

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 α subunit. In the yeast Saccharomyces cerevisiae there are four RGS-homologous proteins (Sst2, Rgs2, Rax1, and Mdm1) and two Gα 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.

Original languageEnglish (US)
Pages (from-to)330-346
Number of pages17
JournalEukaryotic Cell
Volume5
Issue number2
DOIs
StatePublished - Feb 2006
Externally publishedYes

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Pheromones
GTP-Binding Protein Regulators
G-proteins
pheromones
Saccharomyces cerevisiae
Yeasts
GTP-Binding Proteins
Genome
yeasts
genome
RGS Proteins
GTP Phosphohydrolases
Gene Deletion
Protein Subunits
G-Protein-Coupled Receptors
mutants
gene deletion
guanosinetriphosphatase
protein subunits
proteins

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Microbiology

Cite this

Genome-scale analysis reveals Sst2 as the principal regulator of mating pheromone signaling in the yeast Saccharomyces cerevisiae. / Chasse, Scott A.; Flanary, Paul; Parnell, Stephen C.; Hao, Nan; Cha, Jiyoung; Siderovski, David P.; Dohlman, Henrik G.

In: Eukaryotic Cell, Vol. 5, No. 2, 02.2006, p. 330-346.

Research output: Contribution to journalArticle

Chasse, Scott A. ; Flanary, Paul ; Parnell, Stephen C. ; Hao, Nan ; Cha, Jiyoung ; Siderovski, David P. ; Dohlman, Henrik G. / Genome-scale analysis reveals Sst2 as the principal regulator of mating pheromone signaling in the yeast Saccharomyces cerevisiae. In: Eukaryotic Cell. 2006 ; Vol. 5, No. 2. pp. 330-346.
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