A novel regulator of G protein signalling in yeast, Rgs2, downregulates glucose‐activation of the cAMP pathway through direct inhibition of Gpa2
A novel regulator of G protein signalling in yeast, Rgs2, downregulates glucose‐activation of the cAMP pathway through direct inhibition of Gpa2
复制标题
DOI：
10.1093/emboj/18.20.5577
复制
发表时间：
1999-10
期刊：
影响因子：
--
通讯作者：
M. Versele;J. D. de Winde;J. Thevelein
中科院分区：
文献类型：
--
作者：
M. Versele;J. D. de Winde;J. Thevelein
我们已经鉴定了最近在酿酒酵母中发现的异源三聚体G蛋白信号（RGS）调节家族的新成员。YOR107w/RGS2基因作为葡萄糖诱导的固定相细胞耐热性丧失的多拷贝抑制基因被分离出来。Rgs2蛋白的n端一半由一个典型的RGS结构域组成。Rgs2的缺失和过表达分别增强和减少葡萄糖诱导的cAMP积累。RGS2过表达会产生与cAMP依赖性蛋白激酶A （PKA）活性低一致的表型，如海藻糖和糖原积累增强、耐热性增强和STRE控制基因表达升高。RGS2的缺失导致相反的表型。我们证明Rgs2作为葡萄糖诱导的cAMP信号的负调节因子，通过GTPase直接激活Gs - α蛋白Gpa2。Rgs2和Gpa2是酵母中发现的第二个同源的RGS-G - α蛋白对，除了交配信息素途径调节因子Sst2和Gpa1。此外，Rgs2和Sst2具有特异性、非重叠的功能，Rgs2和Sst2的缺失突变体在一定程度上被不同的哺乳动物RGS蛋白补充。
We have characterized a novel member of the recently identified family of regulators of heterotrimeric G protein signalling (RGS) in the yeast Saccharomyces cerevisiae. The YOR107w/RGS2 gene was isolated as a multi‐copy suppressor of glucose‐induced loss of heat resistance in stationary phase cells. The N–terminal half of the Rgs2 protein consists of a typical RGS domain. Deletion and overexpression of Rgs2, respectively, enhances and reduces glucose‐induced accumulation of cAMP. Overexpression of RGS2 generates phenotypes consistent with low activity of cAMP‐dependent protein kinase A (PKA), such as enhanced accumulation of trehalose and glycogen, enhanced heat resistance and elevated expression of STRE‐controlled genes. Deletion of RGS2 causes opposite phenotypes. We demonstrate that Rgs2 functions as a negative regulator of glucose‐induced cAMP signalling through direct GTPase activation of the Gs‐α protein Gpa2. Rgs2 and Gpa2 constitute the second cognate RGS–G‐α protein pair identified in yeast, in addition to the mating pheromone pathway regulators Sst2 and Gpa1. Moreover, Rgs2 and Sst2 exert specific, non‐overlapping functions, and deletion mutants in Rgs2 and Sst2 are complemented to some extent by different mammalian RGS proteins.