Phosphorylation of eukaryotic initiation factor 2 by heme-regulated inhibitor kinase-related protein kinases in Schizosaccharomyces pombe is important for fesistance to environmental stresses.
Phosphorylation of eukaryotic initiation factor 2 by heme-regulated inhibitor kinase-related protein kinases in Schizosaccharomyces pombe is important for fesistance to environmental stresses.
复制标题
粟酒裂殖酵母中血红素调节抑制剂激酶相关蛋白激酶对真核起始因子 2 的磷酸化对于抵抗环境胁迫非常重要。
DOI：
10.1128/mcb.22.20.7134-7146.2002
复制
发表时间：
2002
影响因子：
5.3
通讯作者：
Wek,RonaldC
中科院分区：
文献类型：
--
作者：
Zhan,Ke;Vattem,KrishnaM;Bauer,BettinaN;Dever,ThomasE;Chen,Jane-Jane;Wek,RonaldC
蛋白质合成受真核起始因子 2 (eIF2α) α 亚基的磷酸化调节，以响应不同的环境胁迫。 eIF2α 激酶家族的成员之一，血红素调节抑制剂激酶 (HRI)，在血红素缺乏的条件下被激活，并阻断哺乳动物红系细胞中的蛋白质合成，主要是球蛋白。我们从粟酒裂殖酵母中鉴定出两种与 HRI 相关的激酶，它们与哺乳动物 HRI 具有全长同源性。这两种 HRI 相关激酶（名为 Hri1p 和 Hri2p）表现出对 eIF2α Ser-51 特异的自激酶和激酶活性，并且这两种活性在体外均被氯高铁血红素抑制，如之前针对哺乳动物 HRI 的描述。 Hri1p、Hri2p 或人 eIF2α 激酶、双链 RNA 依赖性蛋白激酶 (PKR) 的过度表达会阻碍 S 的生长。 pombede 是由于 eIF2α 磷酸化升高所致。来自具有单独或组合的thehri1+和hri2+基因缺失的菌株的细胞在暴露于热休克或砷化合物时表现出生长速率降低。 eIF2α 体内磷酸化的测量表明，Hri1p 和 Hri2p 响应这些应激条件而差异磷酸化 eIF2α。这些结果表明，HRI 相关酶并非脊椎动物所独有，并表明这些 eIF2α 激酶是一些低等真核生物中多种应激反应途径的重要参与者。
Protein synthesis is regulated by the phosphorylation of the α subunit of eukaryotic initiation factor 2 (eIF2α) in response to different environmental stresses. One member of the eIF2α kinase family, heme-regulated inhibitor kinase (HRI), is activated under heme-deficient conditions and blocks protein synthesis, principally globin, in mammalian erythroid cells. We identified two HRI-related kinases fromSchizosaccharomyces pombewhich have full-length homology with mammalian HRI. The two HRI-related kinases, named Hri1p and Hri2p, exhibit autokinase and kinase activity specific for Ser-51 of eIF2α, and both activities were inhibited in vitro by hemin, as previously described for mammalian HRI. Overexpression of Hri1p, Hri2p, or the human eIF2α kinase, double-stranded-RNA-dependent protein kinase (PKR), impeded growth ofS. pombedue to elevated phosphorylation of eIF2α. Cells from strains with deletions of thehri1+andhri2+genes, individually or in combination, exhibited a reduced growth rate when exposed to heat shock or to arsenic compounds. Measurements of in vivo phosphorylation of eIF2α suggest that Hri1p and Hri2p differentially phosphorylate eIF2α in response to these stress conditions. These results demonstrate that HRI-related enzymes are not unique to vertebrates and suggest that these eIF2α kinases are important participants in diverse stress response pathways in some lower eukaryotes.