Inhibition of C-protein-mediated MAP kinase activation by a new mammalian gene family
Inhibition of C-protein-mediated MAP kinase activation by a new mammalian gene family
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DOI：
10.1038/379742a0
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发表时间：
1996-02-22
期刊：
影响因子：
64.8
通讯作者：
Kehrl, JH
中科院分区：
文献类型：
--
作者：
Druey, KM;Blumer, KJ;Kehrl, JH
信号转导通路的一般特性是长时间的刺激会降低反应性，这种现象称为脱敏。交配信息素刺激的酵母细胞激活异源三聚体G蛋白连接的MAP激酶依赖性信号通路，诱导G1期细胞周期停滞和形态分化（参考文献1，2）。最终，细胞对信息素脱敏并恢复生长（3）。遗传研究已经证明了使用SST 2基因产物Sst 2 p的脱敏机制的相对重要性（4-7）。在这里，我们确定了一个哺乳动物基因家族称为RGS（G蛋白信号的调节器），编码Sst 2 p的结构和功能同源物。将RGS家族成员引入酵母中通过信息素反应途径减弱信号转导。与SST 2（参考文献8-10）一样，它们在上游或G蛋白水平负调控该途径。RGS家族成员也明显损害哺乳动物G蛋白连接受体对MAP激酶的激活，表明哺乳动物细胞中存在SST 2样脱敏机制及其重要性。
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(3). Genetic studies have demonstrated the relative importance of a desensitization mechanism that uses the SST2 gene product, Sst2p(4-7). 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.