Phosphorylation of the S. cerevisiae Cdc25 in response to glucose results in its dissociation from Ras
Phosphorylation of the S. cerevisiae Cdc25 in response to glucose results in its dissociation from Ras
复制标题
酿酒酵母 Cdc25 响应葡萄糖的磷酸化导致其与 Ras 解离
作者：
E. Gross;D. Goldberg;A. Levitzki
在酿酒酵母中，向饥饿的细胞中添加葡萄糖会触发细胞内环 AMP 水平的短暂升高，从而诱导蛋白质磷酸化级联反应1。葡萄糖信号由 Cdc25/Ras/腺苷酸环化酶途径 2 处理，其中 Cdc25 的作用是催化 Ras3 上的 GDP-GTP 交换。调节 Cdc25 活性的分子机制尚不清楚。我们在这里报告使用高选择性抗 Cdc25 抗体4来证明 Cdc25 是一种磷酸蛋白，并且响应葡萄糖，它在几秒钟内被环 AMP 依赖性蛋白激酶过度磷酸化。还证明，伴随着过度磷酸化，Cdc25 部分重新定位到细胞质，降低了其对膜结合 Ras 的可及性。这些结果具有普遍意义，因为从酵母到哺乳动物，Ras-鸟苷酸交换因子的序列高度保守。
IN the yeast Sacchromyces cerevisiae, addition of glucose to starved cells triggers a transient rise in the intracellular level of cyclic AMP that induces a protein phosphorylation cascade1. The glucose signal is processed by the Cdc25/Ras/adenylyl cyclase pathway2, where the role of Cdc25 is to catalyse the GDP–GTP exchange on Ras3. The molecular mechanisms involved in the regulation of the activity of Cdc25 are unknown. We report here the use of highly selective anti-Cdc25 antibodies4 to demonstrate that Cdc25 is a phospho protein and that in response to glucose it is hyper-phosphorylated, within seconds, by the cyclic AMP-dependent protein kinase. It is also demonstrated that, concomitantly with hyperphosphorylation, Cdc25 partially relocalizes to the cytoplasm, reducing its accessibility to membrane-bound Ras. These results are of general significance because of the highly conserved sequence of Ras–guanyl nucleotide exchange factors from yeasts to mammals.