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

Kirk M. Druey, Kendall J. Blumer, Veronica H. Kang, John H. Kehrl

Research output: Contribution to journalArticlepeer-review

399 Scopus citations

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 growth3. Genetic studies have demonstrated the relative importance of a desensitization mechanism that uses the SST2 gene product, Sst2p+7. 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.

Original languageEnglish
Pages (from-to)742-749
Number of pages8
JournalNature
Volume379
Issue number6567
DOIs
StatePublished - Feb 22 1996

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