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首页> 外文期刊>Proceedings of the National Academy of Sciences of the United States of America >Glucose sensing and signaling in Saccharomyces cerevisiae through the Rgt2 glucose sensor and casein kinase I
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Glucose sensing and signaling in Saccharomyces cerevisiae through the Rgt2 glucose sensor and casein kinase I

机译：通过Rgt2葡萄糖传感器和酪蛋白激酶I在酿酒酵母中进行葡萄糖感测和信号转导

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摘要

The yeast Saccharomyces cerevisiae senses glucose through two transmembrane glucose sensors, Snf3 and Rgt2. Extracellular glucose causes these sensors to generate an intracellular signal that induces expression of HXT genes encoding glucose transporters by inhibiting the function of Rgt1, a transcriptional repressor of HXT genes. We present the following evidence that suggests that the glucose sensors are coupled to the membrane-associated protein kinase casein kinase I (Yck1). (ⅰ) Overexpression of Yck1 leads to constitutive HXT1 expression; (ⅱ) Yck1 (or its paralogue Yck2) is required for glucose induction of HXT1 expression; (ⅲ) Yck1 interacts with the Rgt2 glucose sensor; and (ⅳ) attaching the C-terminal cytoplasmic tail of Rgt2 to Yck1 results in a constitutive glucose signal. The likely targets of Yck1 in this signal transduction pathway are Mth1 and Std1, which bind to and regulate function of the Rgt1 transcription factor and bind to the C-terminal cytoplasmic domain of glucose sensors. Potential casein kinase I phosphoryla-tion sites in Mth1 and Std1 are required for normal glucose regulation of HXT1 expression, and Yck1 catalyzes phosphoryla-tion of Mth1 and Std1 in vitro. These results support a model of glucose signaling in which glucose binding to the glucose sensors causes them to activate Yck1 in the cell membrane, which then phosphorylates Mth1 and Std1 bound to the cytoplasmic face of the glucose sensors, triggering their degradation and leading to the derepression of HXT gene expression. Our results add nutrient sensing to the growing list of processes in which casein kinase I is involved.
机译：酵母酿酒酵母通过两个跨膜葡萄糖传感器Snf3和Rgt2感应葡萄糖。细胞外葡萄糖使这些传感器产生细胞内信号，该信号通过抑制HXT基因的转录阻遏物Rgt1的功能来诱导编码葡萄糖转运蛋白的HXT基因的表达。我们提供以下证据，表明葡萄糖传感器耦合到膜相关的蛋白激酶酪蛋白激酶I（Yck1）。 （ⅰ）Yck1的过表达导致HXT1组成型表达； （ⅱ）Yck1（或其旁系同源物Yck2）是葡萄糖诱导HXT1表达所必需的； （ⅲ）Yck1与Rgt2葡萄糖传感器相互作用； （ⅳ）将Rgt2的C末端胞质尾连接到Yck1，产生组成型葡萄糖信号。 Yck1在此信号转导途径中可能的靶标是Mth1和Std1，它们结合并调节Rgt1转录因子的功能并结合到葡萄糖传感器的C端胞质域。 Mth1和Std1中的潜在酪蛋白激酶I磷酸化位点是正常葡萄糖调节HXT1表达所需的，而Yck1在体外催化Mth1和Std1的磷酸化。这些结果支持了葡萄糖信号传导的模型，其中葡萄糖与葡萄糖传感器的结合使它们激活细胞膜中的Yck1，然后使结合到葡萄糖传感器细胞质面上的Mth1和Std1磷酸化，触发其降解并导致抑制作用HXT基因表达我们的结果为越来越多涉及酪蛋白激酶I的过程增加了营养感测。

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