A novel regulator of G protein signalling in yeast, Rgs2, downregulates glucose-activation of the cAMP pathway through direct inhibition of Gpa2

EMBO J. 1999 Oct 15;18(20):5577-91. doi: 10.1093/emboj/18.20.5577.

Abstract

We have characterized a novel member of the recently identified family of regulators of heterotrimeric G protein signalling (RGS) in the yeast Saccharomyces cerevisiae. The YOR107w/RGS2 gene was isolated as a multi-copy suppressor of glucose-induced loss of heat resistance in stationary phase cells. The N-terminal half of the Rgs2 protein consists of a typical RGS domain. Deletion and overexpression of Rgs2, respectively, enhances and reduces glucose-induced accumulation of cAMP. Overexpression of RGS2 generates phenotypes consistent with low activity of cAMP-dependent protein kinase A (PKA), such as enhanced accumulation of trehalose and glycogen, enhanced heat resistance and elevated expression of STRE-controlled genes. Deletion of RGS2 causes opposite phenotypes. We demonstrate that Rgs2 functions as a negative regulator of glucose-induced cAMP signalling through direct GTPase activation of the Gs-alpha protein Gpa2. Rgs2 and Gpa2 constitute the second cognate RGS-G-alpha protein pair identified in yeast, in addition to the mating pheromone pathway regulators Sst2 and Gpa1. Moreover, Rgs2 and Sst2 exert specific, non-overlapping functions, and deletion mutants in Rgs2 and Sst2 are complemented to some extent by different mammalian RGS proteins.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cyclic AMP / metabolism
  • Down-Regulation
  • Fungal Proteins / antagonists & inhibitors*
  • Fungal Proteins / genetics
  • Fungal Proteins / metabolism*
  • GTP-Binding Protein alpha Subunits*
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • GTP-Binding Proteins / metabolism*
  • GTPase-Activating Proteins*
  • Gene Deletion
  • Gene Expression
  • Genes, Fungal
  • Genetic Complementation Test
  • Glucose / pharmacology
  • Guanosine Triphosphate / metabolism
  • Heterotrimeric GTP-Binding Proteins / antagonists & inhibitors*
  • Heterotrimeric GTP-Binding Proteins / metabolism
  • Hydrolysis
  • Mice
  • Molecular Sequence Data
  • Phenotype
  • RGS Proteins / genetics
  • RGS Proteins / metabolism*
  • Saccharomyces cerevisiae / drug effects
  • Saccharomyces cerevisiae / genetics
  • Saccharomyces cerevisiae / metabolism
  • Saccharomyces cerevisiae Proteins*
  • Sequence Homology, Amino Acid
  • Signal Transduction

Substances

  • Fungal Proteins
  • GTP-Binding Protein alpha Subunits
  • GTPase-Activating Proteins
  • RGS Proteins
  • Rgs2 protein, mouse
  • SST2 protein, S cerevisiae
  • Saccharomyces cerevisiae Proteins
  • Guanosine Triphosphate
  • Cyclic AMP
  • GTP-Binding Proteins
  • GPA1 protein, S cerevisiae
  • GTP-Binding Protein alpha Subunits, Gq-G11
  • Gpa2 protein, S cerevisiae
  • Heterotrimeric GTP-Binding Proteins
  • Glucose