Silljé H H, ter Schure E G, Verkleij A J, Boonstra J, Verrips C T
Department of Molecular Cell Biology, Utrecht University, The Netherlands.
Microbiology (Reading). 1996 Jul;142 ( Pt 7):1765-73. doi: 10.1099/13500872-142-7-1765.
The essential CDC25 gene product of Saccharomyces cerevisiae is the most upstream known component of the RAS/adenylate cyclase pathway. Cdc25 is a GTP-exchange protein involved in activating RAS in response to fermentable carbon sources. In this paper it is reported that the Cdc25 protein, in addition to its stimulatory role in the RAS/adenylate cyclase pathway, regulates glucose transport. Continuous culture studies and glucose uptake experiments showed that the cdc25-1 and the cdc25-5 temperature-sensitive mutants exhibit decreased glucose uptake activity at the restrictive temperature under both repressed and derepressed conditions as compared to the wild-type strain. Because the cdc25-1 mutant is not impaired in its cAMP metabolism, it is concluded that this effect on glucose transport is independent of cAMP levels. Furthermore, it is shown that the decrease in glucose uptake activity is not due to a decrease in protein synthesis or to an arrest in the G1 phase of the cell cycle. In addition to a defect in glucose uptake, the cdc25-5 mutant strain exhibited differences in glucose metabolism, probably due to the decreased cAMP level and hence decreased protein kinase A activity. Because the Cdc25 protein is localized at the membrane, these results indicate that Cdc25 is directly involved in glucose transport and may be in direct contact with the glucose transporters.
酿酒酵母的必需基因CDC25产物是RAS/腺苷酸环化酶途径中已知的最上游成分。Cdc25是一种鸟嘌呤核苷酸交换蛋白，参与响应可发酵碳源激活RAS。本文报道，Cdc25蛋白除了在RAS/腺苷酸环化酶途径中起刺激作用外，还调节葡萄糖转运。连续培养研究和葡萄糖摄取实验表明，与野生型菌株相比，cdc25 - 1和cdc25 - 5温度敏感突变体在限制温度下，在阻遏和去阻遏条件下均表现出葡萄糖摄取活性降低。由于cdc25 - 1突变体的cAMP代谢未受损，得出结论：这种对葡萄糖转运的影响与cAMP水平无关。此外，表明葡萄糖摄取活性的降低不是由于蛋白质合成减少或细胞周期G1期停滞。除了葡萄糖摄取缺陷外，cdc25 - 5突变体菌株在葡萄糖代谢方面表现出差异，可能是由于cAMP水平降低，从而蛋白激酶A活性降低。由于Cdc25蛋白定位于细胞膜，这些结果表明Cdc25直接参与葡萄糖转运，并且可能与葡萄糖转运体直接接触。
