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Nature

Title:		Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family
Author(s):		Druey KM; Blumer KJ; Kang VH; Kehrl JH;
Address:		"Laboratory of Immunoregulation, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland 20892-1876, USA"
Journal Title:		Nature
Year:		1996
Volume:		379
Issue:		6567
Page Number:		742 - 746
DOI:		10.1038/379742a0
ISSN/ISBN:		0028-0836 (Print) 0028-0836 (Linking)
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"
Keywords:		"Amino Acid Sequence Animals Antigens, CD/metabolism Base Sequence Calcium-Calmodulin-Dependent Protein Kinases/*antagonists & inhibitors/metabolism Cell Line DNA Probes Enzyme Activation Fungal Proteins/genetics GTP-Binding Proteins/antagonists & inhibito;"
Notes:		"MedlineDruey, K M Blumer, K J Kang, V H Kehrl, J H eng Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. England 1996/02/22 Nature. 1996 Feb 22; 379(6567):742-6. doi: 10.1038/379742a0"