Regulation and function of yeast PAS kinase: a role in the maintenance of cellular integrity.
Regulation and function of yeast PAS kinase: a role in the maintenance of cellular integrity.
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DOI：
10.4161/cc.8.12.8799
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发表时间：
2009-06-15
期刊：
影响因子：
--
通讯作者：
Rutter J
中科院分区：
文献类型：
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作者：
Grose JH;Sundwall E;Rutter J
无法协调细胞代谢过程与细胞和有机体营养环境导致各种疾病，包括糖尿病和肥胖症。AMPK和mTOR等营养传感蛋白激酶在代谢调节中发挥着关键作用，是治疗疾病的有前途的治疗靶点。在这个额外的视图中，我们描述了另一个成员的营养敏感蛋白激酶组，PAS激酶，它在哺乳动物和酵母的葡萄糖利用的调节中发挥作用。PAS激酶缺陷小鼠对高脂饮食诱导的体重增加、胰岛素抵抗和肝脏甘油三酯过度积累具有抗性，这表明PAS激酶在哺乳动物中调节葡萄糖和脂质代谢中的作用。同样地，PAS激酶缺陷型酵母显示改变的葡萄糖分配，以细胞壁生物合成为代价有利于糖原生物合成。因此，PAS激酶缺陷型酵母对细胞壁干扰剂敏感。这种响应PAS激酶激活的葡萄糖分配是由于Ugp 1的磷酸化，该酶主要负责UDP-葡萄糖的产生。两个酵母PAS激酶同系物，Psk 1和Psk 2，被激活的两个刺激，细胞完整性应力和非发酵碳源。我们回顾什么是已知的酵母PAS激酶和描述的遗传筛选，可能有助于阐明参与PAS激酶的激活和功能的途径。
The inability to coordinate cellular metabolic processes with the cellular and organismal nutrient environment leads to a variety of disorders, including diabetes and obesity. Nutrient-sensing protein kinases, such as AMPK and mTOR, play a pivotal role in metabolic regulation and are promising therapeutic targets for the treatment of disease. In this Extra View, we describe another member of the nutrient-sensing protein kinase group, PAS kinase, which plays a role in the regulation of glucose utilization in both mammals and yeast. PAS kinase deficient mice are resistant to high fat diet-induced weight gain, insulin resistance and hepatic triglyceride hyperaccumulation, suggesting a role for PAS kinase in the regulation of glucose and lipid metabolism in mammals. Likewise, PAS kinase deficient yeast display altered glucose partitioning, favoring glycogen biosynthesis at the expense of cell wall biosynthesis. As a result, PAS kinase deficient yeast are sensitive to cell wall perturbing agents. This partitioning of glucose in response to PAS kinase activation is due to phosphorylation of Ugp1, the enzyme primarily responsible for UDP-glucose production. The two yeast PAS kinase homologs, Psk1 and Psk2, are activated by two stimuli, cell integrity stress and nonfermentative carbon sources. We review what is known about yeast PAS kinase and describe a genetic screen that may help elucidate pathways involved in PAS kinase activation and function.