Plc1p, Arg82p, and Kcs1p, enzymes involved in inositol pyrophosphate synthesis, are essential for phosphate regulation and polyphosphate accumulation in Saccharomyces cerevisiae
Plc1p, Arg82p, and Kcs1p, enzymes involved in inositol pyrophosphate synthesis, are essential for phosphate regulation and polyphosphate accumulation in Saccharomyces cerevisiae
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DOI：
10.1074/jbc.m414579200
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发表时间：
2005-07-01
影响因子：
4.8
通讯作者：
Harashima, S
中科院分区：
文献类型：
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作者：
Auesukaree, C;Tochio, H;Harashima, S
在酿酒酵母中，磷酸信号转导PHO途径参与调节几个磷酸响应基因，如PHO 5，其编码抑制性酸性磷酸酶。在该途径中，细胞周期蛋白依赖性激酶抑制剂（Pho 81 p）调节细胞周期蛋白-细胞周期蛋白依赖性激酶复合物Pho 80 p-Pho 85 p的激酶活性，该复合物响应于细胞内磷酸盐水平磷酸化转录因子Pho 4p。然而，细胞如何感知磷酸盐的可用性并将磷酸盐信号传递给Pho 81 p仍然未知。为了鉴定PHO途径的其他组分，我们筛选了一系列酵母缺失菌株。我们发现，PLC 1，ARG 82，KCS 1，这是参与合成肌醇多磷酸，ADK 1，它编码腺苷酸激酶，组成型表达PHO 5的破坏。这些因子中的每一个都在Pho 81 p的上游起作用，并且独立于细胞内正磷酸盐水平负调节PHO途径。KCS 1的过表达，而不是其他基因，抑制PHO 5在野生型菌株在低磷酸盐条件下的表达。这些结果提高了二磷酸肌醇四磷酸和/或bisdiphosphoinositol三磷酸可能是必不可少的PHO途径的调节的可能性。此外，Delta plc 1，Delta arg 82和Delta kcs 1缺失菌株，但不是Delta ipk 1缺失菌株，具有显著降低的细胞内多磷酸盐水平，表明参与肌醇焦磷酸合成的酶也是多磷酸盐积累所需的。
In Saccharomyces cerevisiae, the phosphate signal transduction PHO pathway is involved in regulating several phosphate-responsive genes such as PHO5, which encodes repressible acid phosphatase. In this pathway, a cyclin-dependent kinase inhibitor (Pho81p) regulates the kinase activity of the cyclin-cyclin-dependent kinase complex Pho80p-Pho85p, which phosphorylates the transcription factor Pho4p in response to intracellular phosphate levels. However, how cells sense phosphate availability and transduce the phosphate signal to Pho81p remains unknown. To identify additional components of the PHO pathway, we have screened a collection of yeast deletion strains. We found that disruptants of PLC1, ARG82, and KCS1, which are involved in the synthesis of inositol polyphosphate, and ADK1, which encodes adenylate kinase, constitutively express PHO5. Each of these factors functions upstream of Pho81p and negatively regulates the PHO pathway independently of intracellular orthophosphate levels. Overexpression of KCS1, but not of the other genes, suppressed PHO5 expression in the wild-type strain under low phosphate conditions. These results raise the possibility that diphosphoinositol tetrakisphosphate and/or bisdiphosphoinositol triphosphate may be essential for regulation of the PHO pathway. Furthermore, the Delta plc1, Delta arg82, and Delta kcs1 deletion strains, but not the Delta ipk1 deletion strain, had significantly reduced intracellular polyphosphate levels, suggesting that enzymes involved in inositol pyrophosphate synthesis are also required for polyphosphate accumulation.