Mitochondrial phosphoglycerate mutase 5 uses alternate catalytic activity as a protein serine/threonine phosphatase to activate ASK1
Mitochondrial phosphoglycerate mutase 5 uses alternate catalytic activity as a protein serine/threonine phosphatase to activate ASK1
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DOI：
10.1073/pnas.0901823106
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发表时间：
2009-07-28
影响因子：
11.1
通讯作者：
Ichijo, Hidenori
中科院分区：
文献类型：
--
作者：
Takeda, Kohsuke;Komuro, Yoshiko;Ichijo, Hidenori
磷酸甘油酸酯酶（PGAM）是一种在糖酵解中将3-磷酸甘油酸转化为2-磷酸甘油酸的中间代谢酶。在这里，我们发现锚定在线粒体膜上的PGAM 5缺乏PGAM活性，而是与MAP激酶激酶激酶ASK 1结合，并作为一种特异性蛋白质Ser/Thr磷酸酶，通过抑制位点的去磷酸化激活ASK 1。PGAM 5中活性位点His-105的突变消除了以ASK 1和磷酸化Thr肽为底物的磷酸酶活性。果蝇和秀丽隐杆线虫的PGAM 5同源物也表现出特异性的Ser/Thr磷酸酶活性，并激活相应的果蝇和秀丽隐杆线虫。线虫ASK 1激酶。PGAM 5与PPP、MPP和FCP家族的其他已知Ser/Thr磷酸酶无关，我们的研究结果表明，PGAM家族的这一成员已从小分子跨越到蛋白质底物，并已适应作为ASK 1的专门激活剂。
Phosphoglycerate mutase (PGAM) is an enzyme of intermediary metabolism that converts 3-phosphoglycerate to 2-phosphoglycerate in glycolysis. Here, we discovered PGAM5 that is anchored in the mitochondrial membrane lacks PGAM activity and instead associates with the MAP kinase kinase kinase ASK1 and acts as a specific protein Ser/Thr phosphatase that activates ASK1 by dephosphorylation of inhibitory sites. Mutation of an active site His-105 in PGAM5 abolished phosphatase activity with ASK1 and phospho-Thr peptides as substrates. The Drosophila and Caenorhabditis elegans orthologs of PGAM5 also exhibit specific Ser/Thr phosphatase activity and activate the corresponding Drosophila and C. elegans ASK1 kinases. PGAM5 is unrelated to the other known Ser/Thr phosphatases of the PPP, MPP, and FCP families, and our results suggest that this member of the PGAM family has crossed over from small molecules to protein substrates and been adapted to serve as a specialized activator of ASK1.