Glucose-6-P control of glycogen synthase phosphorylation in yeast
Glucose-6-P control of glycogen synthase phosphorylation in yeast
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DOI：
10.1074/jbc.272.36.22495
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发表时间：
1997-09-05
影响因子：
4.8
通讯作者：
Roach, PJ
中科院分区：
文献类型：
--
作者：
Huang, DQ;Wilson, WA;Roach, PJ
SNF1基因编码一种蛋白激酶，该激酶对于葡萄糖可阻遏基因的表达以及储存多糖糖原的合成是必需的。通过遗传筛选，我们发现编码6 - 磷酸果糖 - 1 - 激酶β亚基的PFK2基因发生突变后，可恢复snf1细胞中的糖原积累。PFK2的缺失导致代谢物（如葡萄糖 - 6 - 磷酸）水平升高、糖原过度积累以及糖原合酶的激活，而葡萄糖 - 6 - 磷酸在snf1细胞中是降低的。其他增加葡萄糖 - 6 - 磷酸的突变，如编码6 - 磷酸果糖 - 1 - 激酶α亚基的PFK1基因的缺失，或者磷酸葡萄糖异构酶基因PGI1的缺失，对糖原代谢的影响与pfk2突变体相似。我们提出，升高的葡萄糖 - 6 - 磷酸介导了这些突变对糖原储存的影响。从pfk2细胞中提取的糖原合酶激酶活性降低，但如果将提取物进行凝胶过滤以去除小分子，则其活性可恢复到野生型水平。此外，添加葡萄糖 - 6 - 磷酸可抑制野生型细胞提取物中的糖原合酶激酶活性，在约2 mM时达到半数抑制。我们认为葡萄糖 - 6 - 磷酸通过两种不同的机制控制糖原合酶的活性。首先，葡萄糖 - 6 - 磷酸是糖原合酶的直接激活剂；其次，它通过抑制一种糖原合酶激酶来控制糖原合酶的磷酸化状态。
The SNF1 gene encodes a protein kinase necessary for expression of glucose-repressible genes and for the synthesis of the storage polysaccharide glycogen, From a genetic screen, we have found that mutation of the PFK2 gene, which encodes the beta-subunit of 6-phosphofructo-1-kinase, restores glycogen accumulation in snf1 cells. Loss of PFK2 causes elevated levels of metabolites such as glucose-6-P, hyperaccumulation of glycogen, and activation of glycogen synthase, whereas glucose-6-P is reduced in snf1 cells, Other mutations that increase glucose-6-P, deletion of PFK1, which codes for the alpha-subunit of 6-phosphofructo-1-kinase, or of PGI1, the phosphoglucoisomerase gene, had similar effects on glycogen metabolism as did pfk2 mutants. We propose that elevated glucose-g-P mediates the effects of these mutations on glycogen storage. Glycogen synthase kinase activity was reduced in extracts from pfk2 cells but was restored to that of wild type if the extract was gel-filtered to remove small molecules, Also, added glucose-6-P inhibited the glycogen synthase kinase activity in extracts from wild-type cells, half-maximally at similar to 2 mM. We suggest that glucose-6-P controls glycogen synthase activity by two separate mechanisms. First, glucose-6-P is a direct activator of glycogen synthase, and second, it controls the phosphorylation state of glycogen synthase by inhibiting a glycogen synthase kinase.