Mutations that alter the third cytoplasmic loop of the a-factor receptor lead to a constitutive and hypersensitive phenotype.
Mutations that alter the third cytoplasmic loop of the a-factor receptor lead to a constitutive and hypersensitive phenotype.
复制标题
改变α因子受体第三个细胞质环的突变会导致组成型和过敏表型。
DOI：
10.1073/pnas.90.21.9921
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发表时间：
1993
影响因子：
11.1
通讯作者：
SpragueJr,GF
中科院分区：
文献类型：
--
作者：
Boone,C;Davis,NG;SpragueJr,GF
酿酒酵母的STE3基因编码一种G蛋白偶联受体，该受体对交配信息素a因子具有特异性。ste3L194Q突变导致受体第三细胞质环内的谷氨酰胺取代亮氨酸-194，导致信息素敏感性增加20倍，并引起反应途径的部分组成性激活。此外，194位的其他氨基酸替换和几个缺失突变共同去除大部分第三细胞质环，导致受体过度活跃。因此，我们认为第三个细胞质环的一个作用是作为一个负调控域参与维持受体的非信号状态。ste3L194Q细胞的组成活性和信息素超敏性是隐性的，表明野生型受体可以拮抗与激活受体相关的信号。ste3 delta 306突变导致受体大部分c端结构域的截断，导致信息素敏感性增加20倍，表明该结构域也介导受体的负调控。ste3L194Q和ste3 delta 306突变似乎独立影响受体活性，因为双突变与信息素敏感性增加400倍有关。
The STE3 gene of Saccharomyces cerevisiae encodes a G protein-coupled receptor that is specific for the mating pheromone a-factor. The ste3L194Q mutation, which leads to the substitution of glutamine for leucine-194 within the third cytoplasmic loop of the receptor, resulted in a 20-fold increase in pheromone sensitivity and also caused partial constitutive activation of the response pathway. Moreover, other amino acid substitutions at the 194 position and several deletion mutations that collectively remove most of the third cytoplasmic loop resulted in hyperactive receptors. Therefore, we suggest that one role of the third cytoplasmic loop is to function as a negative regulatory domain involved in the maintenance of a nonsignaling state of the receptor. The constitutive activity and the pheromone hypersensitivity of ste3L194Q cells were recessive, suggesting that the wild-type receptor can antagonize the signal associated with the activated receptor. The ste3 delta 306 mutation, which results in truncation of most of the C-terminal domain of the receptor, led to a 20-fold increase in pheromone sensitivity, indicating that this domain also mediates negative regulation of the receptor. The ste3L194Q and ste3 delta 306 mutations appear to affect receptor activity independently, because the double mutant was associated with a 400-fold increase in pheromone sensitivity.