Abstract
A general property of signal transduction pathways is that prolonged stimulation decreases responsiveness, a phenomenon termed desensitization. Yeast cells stimulated with mating pheromone activate a heterotrimeric G-protein-linked, MAP-kinase-dependent signalling pathway that induces G1-phase cell-cycle arrest and morphological differentiation (reviewed in refs 1, 2). Eventually the cells desensitize to pheromone and resume growth. Genetic studies have demonstrated the relative importance of a desensitization mechanism that uses the SST2 gene product, Sst2p. Here we identify a mammalian gene family termed RGS (for regulator of G-protein signalling) that encodes structural and functional homologues of Sst2p. Introduction of RGS family members into yeast blunts signal transduction through the pheromone-response pathway. Like SST2 (refs 8-10), they negatively regulate this pathway at a point upstream or at the level of the G protein. The RGS family members also markedly impair MAP kinase activation by mammalian G-protein-linked receptors, indicating the existence and importance of an SST2-like desensitization mechanism in mammalian cells.
Publication types
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Research Support, Non-U.S. Gov't
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Research Support, U.S. Gov't, P.H.S.
MeSH terms
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Amino Acid Sequence
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Animals
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Antigens, CD / metabolism
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Base Sequence
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Calcium-Calmodulin-Dependent Protein Kinases / antagonists & inhibitors*
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Calcium-Calmodulin-Dependent Protein Kinases / metabolism
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Cell Line
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DNA Probes
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Enzyme Activation
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Fungal Proteins / genetics
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GTP-Binding Proteins / antagonists & inhibitors
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GTP-Binding Proteins / metabolism*
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GTPase-Activating Proteins*
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Humans
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases*
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Molecular Sequence Data
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Multigene Family*
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Pheromones / metabolism
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Proteins / genetics
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Proteins / metabolism*
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RGS Proteins*
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Rats
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Receptors, Interleukin / metabolism
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Receptors, Interleukin-8A
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Recombinant Proteins / metabolism
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Repressor Proteins*
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Saccharomyces cerevisiae Proteins*
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Sequence Alignment
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Signal Transduction
Substances
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Antigens, CD
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DNA Probes
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Fungal Proteins
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GTPase-Activating Proteins
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Pheromones
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Proteins
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RGS Proteins
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RGS3 protein, human
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Receptors, Interleukin
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Receptors, Interleukin-8A
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Recombinant Proteins
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Repressor Proteins
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Rgs3 protein, mouse
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Rgs3 protein, rat
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SST2 protein, S cerevisiae
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Saccharomyces cerevisiae Proteins
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RGS4 protein
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Calcium-Calmodulin-Dependent Protein Kinases
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Mitogen-Activated Protein Kinase 3
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Mitogen-Activated Protein Kinases
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GTP-Binding Proteins
Associated data
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GENBANK/U27655
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GENBANK/U27767
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GENBANK/U27768