| First Author | Druey KM | Year | 1996 |
| Journal | Nature | Volume | 379 |
| Issue | 6567 | Pages | 742-6 |
| PubMed ID | 8602223 | Mgi Jnum | J:31469 |
| Mgi Id | MGI:78977 | Doi | 10.1038/379742a0 |
| Citation | Druey KM, et al. (1996) Inhibition of G-protein-mediated MAP kinase activation by a new mammalian gene family. Nature 379(6567):742-6 |
| abstractText | 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. |
