Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family

Nature
K M DrueyJ H Kehrl

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.

References

Aug 15, 1991·Proceedings of the National Academy of Sciences of the United States of America·R J DohmenA Varshavsky
May 24, 1991·Science·A LupasJ Stock
Sep 1, 1989·Molecular and Cellular Biology·D Blinder, D D Jenness
Nov 1, 1993·Molecular and Cellular Biochemistry·J Van LintJ R Vandenheede
Sep 2, 1994·Science·K Madura, A Varshavsky
Jan 1, 1993·Annual Review of Genetics·J Kurjan
May 12, 1994·Nature·J M KyriakisJ R Woodgett
Dec 5, 1995·Proceedings of the National Academy of Sciences of the United States of America·L De VriesM G Farquhar

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Citations

Apr 23, 2002·Journal of Cellular Biochemistry·Kannan ThirunavukkarasuJude E Onyia
Apr 10, 2007·Journal of Molecular Neuroscience : MN·Avi RimlerNava Zisapel
Aug 7, 2013·Applied Microbiology and Biotechnology·Yunchuan WangJinkui Yang
May 2, 2001·Biochemical Pharmacology·J Sondek, D P Siderovski
Apr 25, 2003·Experimental and Molecular Pathology·Lisa PatroneMichael A Teitell
Aug 27, 1999·Trends in Pharmacological Sciences·J R Hepler
Dec 26, 2001·Biochimica Et Biophysica Acta·C A DoupnikJ M Shinaman
Nov 19, 1997·Progress in Neurobiology·A F Rocha
Dec 24, 1998·Molecular and Cellular Endocrinology·B NitzJ Olcese
Apr 17, 2002·Cellular Signalling·Alison W GagnonRobert J Leadley
Nov 11, 2003·Cellular Signalling·Xiao Yu LiMichael T Greenwood
Jan 5, 2000·Cellular Signalling·A Kikuchi
Apr 1, 1997·Current Opinion in Cell Biology·M R Koelle
Feb 1, 1997·Current Opinion in Genetics & Development·E LebererM Whiteway
May 4, 1999·Trends in Cell Biology·L De Vries, M Gist Farquhar
Apr 15, 2008·Trends in Endocrinology and Metabolism : TEM·G Milligan
Jan 27, 2000·Cytokine & Growth Factor Reviews·A Kikuchi
Nov 25, 2003·Nature Cell Biology·Eric N JohnsonKirk M Druey
Oct 29, 2013·Nature Immunology·Laura K MackayThomas Gebhardt
Oct 17, 1998·British Journal of Pharmacology·M SchindlerP P Humphrey
Sep 14, 2001·Genes to Cells : Devoted to Molecular & Cellular Mechanisms·P S Pereira, N C Jones
Feb 1, 2011·The Journal of Biological Chemistry·Zhao YangKirk M Druey
Dec 5, 1998·DNA and Cell Biology·T ElmoreD P Smith
Jan 27, 2005·Thyroid : Official Journal of the American Thyroid Association·Anke TönjesRalf Paschke

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