A novel regulator of G protein signalling in yeast, Rgs2, downregulates glucose-activation of the cAMP pathway through direct inhibition of Gpa2.
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.
Versele
M
M
Laboratorium voor Moleculaire Celbiologie, Instituut voor Plantkunde en Microbiologie, Katholieke Universiteit Leuven, Kardinaal Mercierlaan 92, B-3001 Leuven-Heverlee, Flanders, Belgium.
de Winde
J H
JH
Thevelein
J M
JM
D000595:Amino Acid Sequence; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D015536:Down-Regulation; D005656:Fungal Proteins / Q000037:antagonists & inhibitors* / Q000235:genetics / Q000378:metabolism*; D044385:GTP-Binding Protein alpha Subunits; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; D019204:GTP-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D017353:Gene Deletion; D015870:Gene Expression; D005800:Genes, Fungal; D005816:Genetic Complementation Test; D005947:Glucose / Q000494:pharmacology; D006160:Guanosine Triphosphate / Q000378:metabolism; D020962:Heterotrimeric GTP-Binding Proteins / Q000037:antagonists & inhibitors* / Q000378:metabolism; D006868:Hydrolysis; D051379:Mice; D008969:Molecular Sequence Data; D010641:Phenotype; D020710:RGS Proteins / Q000235:genetics / Q000378:metabolism*; D012441:Saccharomyces cerevisiae / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D029701:Saccharomyces cerevisiae Proteins; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction
D005656:Fungal Proteins; D044385:GTP-Binding Protein alpha Subunits; D020690:GTPase-Activating Proteins; D020710:RGS Proteins; C105345:Rgs2 protein, mouse; C094301:SST2 protein, S cerevisiae; D029701:Saccharomyces cerevisiae Proteins; D006160:Guanosine Triphosphate; D000242:Cyclic AMP; D019204:GTP-Binding Proteins; C084293:GPA1 protein, S cerevisiae; D043802:GTP-Binding Protein alpha Subunits, Gq-G11; C083907:Gpa2 protein, S cerevisiae; D020962:Heterotrimeric GTP-Binding Proteins; D005947:Glucose