RAS MEMBRANE TARGETING IS ESSENTIAL FOR GLUCOSE SIGNALING BUT NOT FOR VIABILITY IN YEAST
RAS MEMBRANE TARGETING IS ESSENTIAL FOR GLUCOSE SIGNALING BUT NOT FOR VIABILITY IN YEAST
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DOI：
10.1073/pnas.92.7.2984
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发表时间：
1995-03-28
影响因子：
11.1
通讯作者：
POWERS, S
中科院分区：
文献类型：
--
作者：
BHATTACHARYA, S;CHEN, L;POWERS, S
Ras蛋白是一种小的GTP结合蛋白，在真核细胞的多种信号转导途径中起着重要的传递作用。像大多数后生动物Ras蛋白一样，酵母Ras蛋白通过添加一个法尼基和一个棕榈酰基片段进行翻译后修饰，这些修饰是将蛋白质靶向到质膜的细胞质表面和蛋白质的生物活性所必需的。我们已经构建了酵母（Saccharomyces cerevisiae） Ras的突变体，这些突变体在体内被法尼酰化，但不被棕榈酰化。这些突变蛋白并不局限于质膜，而是在细胞中和野生型蛋白一样起作用，这些突变体是有活力的，但不能诱导细胞内cAMP浓度在葡萄糖添加时的短暂增加，尽管这种缺乏不会产生显著的生长表型。这些结果与假设一致，即酵母Ras上的法尼基片段的基本作用是增强Ras与其主要下游靶点腺苷酸环化酶之间的生产相互作用，而不是将Ras定位到质膜上。
Ras proteins are small GTP binding proteins that serve as critical relays in a variety of signal transduction pathways in eukaryotic cells. Like most metazoan Ras proteins, yeast Ras is post-translationally modified by addition of a farnesyl and a palmitoyl moiety, and these modifications are required for targeting the protein to the cytoplasmic face of the plasma membrane and for biological activity of the protein, We have constructed mutants of the yeast (Saccharomyces cerevisiae) Ras that are farnesylated in vivo but are not palmitoylated. These mutant proteins are not localized to the plasma membrane but function in the cell as well as the wild-type protein, Such mutants are viable but fail to induce a transient increase in intracellular cAMP concentration in response to glucose addition, although this deficiency does not yield a marked growth phenotype. These results are consistent with the hypothesis that the essential role of the farnesyl moiety on yeast Ras is to enhance productive interaction between Ras and its essential downstream target, adenylyl cyclase, rather than to localize Ras to the plasma membrane.