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
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Research Support, Non-U.S. Gov't
MeSH terms
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Amino Acid Sequence
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Animals
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Cyclic AMP / metabolism
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Down-Regulation
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Fungal Proteins / antagonists & inhibitors*
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Fungal Proteins / genetics
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Fungal Proteins / metabolism*
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GTP-Binding Protein alpha Subunits*
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GTP-Binding Protein alpha Subunits, Gq-G11
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GTP-Binding Proteins / metabolism*
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GTPase-Activating Proteins*
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Gene Deletion
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Gene Expression
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Genes, Fungal
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Genetic Complementation Test
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Glucose / pharmacology
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Guanosine Triphosphate / metabolism
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Heterotrimeric GTP-Binding Proteins / antagonists & inhibitors*
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Heterotrimeric GTP-Binding Proteins / metabolism
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Hydrolysis
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Mice
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Molecular Sequence Data
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Phenotype
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RGS Proteins / genetics
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RGS Proteins / metabolism*
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Saccharomyces cerevisiae / drug effects
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Saccharomyces cerevisiae / genetics
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Saccharomyces cerevisiae / metabolism
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Saccharomyces cerevisiae Proteins*
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Sequence Homology, Amino Acid
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Signal Transduction
Substances
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Fungal Proteins
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GTP-Binding Protein alpha Subunits
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GTPase-Activating Proteins
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RGS Proteins
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Rgs2 protein, mouse
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SST2 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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Guanosine Triphosphate
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Cyclic AMP
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GTP-Binding Proteins
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GPA1 protein, S cerevisiae
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GTP-Binding Protein alpha Subunits, Gq-G11
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Gpa2 protein, S cerevisiae
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Heterotrimeric GTP-Binding Proteins
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Glucose