Glucose sensing and signaling in Saccharomyces cerevisiae through the Rgt2 glucose sensor and casein kinase I
Glucose sensing and signaling in Saccharomyces cerevisiae through the Rgt2 glucose sensor and casein kinase I
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DOI：
10.1073/pnas.0305901101
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发表时间：
2004-02-10
影响因子：
11.1
通讯作者：
Johnston, M
中科院分区：
文献类型：
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作者：
Moriya, H;Johnston, M
酿酒酵母通过两个跨膜葡萄糖传感器Snf3和Rgt2来感知葡萄糖。胞外葡萄糖使这些传感器产生胞内信号，通过抑制HXT基因的转录抑制因子Rgt1的功能，诱导编码葡萄糖转运体的HXTgenes的表达。我们提出了以下证据，表明葡萄糖传感器与膜相关蛋白激酶酪蛋白激酶I （Yck1）偶联。(i) Yck1过表达导致构成型HXT1表达；（ii）葡萄糖诱导HXT1表达需要Yck1（或其同源物Yck2）；（iii） Yck1与Rgt2葡萄糖传感器相互作用；（iv）将Rgt2的c端细胞质尾部连接到Yck1上，产生葡萄糖组成信号。Yck1在该信号转导通路中的可能靶点是Mth1和Std1，它们结合并调节Rgt1转录因子的功能，并结合葡萄糖传感器的c端胞质结构域。HXT1表达的正常葡萄糖调节需要Mth1和Std1中潜在的酪蛋白激酶I磷酸化位点，Yck1在体外催化Mth1和Std1的磷酸化。这些结果支持葡萄糖信号模型，其中葡萄糖结合到葡萄糖传感器导致它们激活细胞膜上的Yckl，然后磷酸化结合到葡萄糖传感器细胞质表面的Mthl和Stdl，触发它们的降解并导致HXT基因表达的降低。我们的研究结果为酪蛋白激酶I参与的一系列过程增加了营养感知。
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 HXTgenes 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 phosphorylation sites in Mth1 and Std1 are required for normal glucose regulation of HXT1 expression, and Yck1 catalyzes phosphorylation 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 Yckl in the cell membrane, which then phosphorylates Mthl and Stdl 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.