PMID:8602223

Citation	Druey, KM, Blumer, KJ, Kang, VH and Kehrl, JH (1996) Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family. Nature 379:742-6
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.
Links	PubMed Online version:10.1038/379742a0
Keywords	Amino Acid Sequence; Animals; Antigens, CD/metabolism; Base Sequence; Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors; Calcium-Calmodulin-Dependent Protein Kinases/metabolism; Cell Line; DNA Probes; Enzyme Activation; Fungal Proteins/genetics; GTP-Binding Proteins/antagonists & inhibitors; GTP-Binding Proteins/metabolism; GTPase-Activating Proteins; Humans; Mitogen-Activated Protein Kinase 3; Mitogen-Activated Protein Kinases; Molecular Sequence Data; Multigene Family; Pheromones/metabolism; Proteins/genetics; Proteins/metabolism; RGS Proteins; Rats; Receptors, Interleukin/metabolism; Receptors, Interleukin-8A; Recombinant Proteins/metabolism; Repressor Proteins; Saccharomyces cerevisiae Proteins; Sequence Alignment; Signal Transduction
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Annotations

Gene product	Qualifier	GO Term	Evidence Code	with/from	Aspect	Extension	Notes	Status
HUMAN:RGS4	involved_in	GO:0000188: inactivation of MAPK activity	ECO:0000304: author statement supported by traceable reference used in manual assertion		P		Seeded From UniProt	complete

References

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