Characterization of rainbow trout and zebrafish eukaryotic initiation factor 2α and its response to endoplasmic reticulum stress and IPNV infection
Characterization of rainbow trout and zebrafish eukaryotic initiation factor 2α and its response to endoplasmic reticulum stress and IPNV infection
复制标题
DOI：
10.1016/s0145-305x(02)00096-4
复制
发表时间：
2003-03-01
影响因子：
2.9
通讯作者：
Jagus, R
中科院分区：
文献类型：
--
作者：
Garner, JN;Joshi, B;Jagus, R
虹鳟鱼和斑马鱼eIF 2 α的cDNA已被分离，并发现编码与人翻译起始因子eIF 2的α亚基具有相似分子量和等电点的蛋白质。虹鳟鱼（36.0 kDa）和斑马鱼（36.2 kDa）eIF 2 α分别与人类蛋白质具有93%和91%的同一性，并被针对人类形式的抗体识别。在哺乳动物中，eIF 2 α亚基的磷酸化在响应一系列细胞应激的蛋白质合成调节中发挥着关键作用。与人类磷酸化和激酶对接位点相对应的区域在两种鱼类的蛋白质中是相同的。与eIF 2再循环因子eIF 2B相互作用的残基也是如此。此外，重组虹鳟鱼、鳟鱼和斑马鱼eIF 2 α均可以在体外被哺乳动物血红素敏感性eIF 2 α-激酶HRI/HCR磷酸化。以及干扰素诱导的dsRNA敏感激酶PKR。虹鳟鱼和斑马鱼eIF 2 α的磷酸化也可以在体内发生，RTG-2和ZFL细胞通过用Ca 2 +-离子载体A23187处理而经受内质网（ER）应激，显示eIF 2 α磷酸化水平增加，表明鱼类和其他高等真核生物中的ER应激反应之间的相似性。此外，RTG-2细胞对poly（I）（.）poly（C）或感染性胰腺坏死病毒（IPNV）通过增加eIF 2 α磷酸化而感染。这些数据表明，RTG-2细胞表达干扰素诱导的eIF 2 α-激酶，PKR，并表明干扰素/eIF 2 α/PKR对病毒感染的反应可能是一个保守的脊椎动物的特征。总的来说，这些数据与鱼类能够通过eIF 2 α的磷酸化调节蛋白质合成以响应细胞应激的前提一致。(C)2002爱思唯尔科技有限公司。保留所有权利。
The cDNAs of rainbow trout and zebrafish eIF2alpha have been isolated and found to encode proteins of similar molecular weight and isoelectric point to the alpha-subunit of the human translational initiation factor, eIF2. The rainbow trout (36.0 kDa) and zebrafish (36.2 kDa) eIF2alphas share 93 and 91% identity to the human protein, respectively, and are recognized by antibodies raised to the human form. In mammals, the phosphorylation of the alpha-subunit of eIF2 plays a key role in the regulation of protein synthesis in response to a range of cellular stresses. Regions corresponding to the human phosphorylation and kinase-docking sites are identical in the proteins of both fish species. as are residues that interact with the eIF2 recycling factor, eIF2B. Moreover, both recombinant rainbow, trout and zebrafish eIF2alphas can be phosphorylated in vitro by the mammalian heme-sensitive eIF2alpha-kinase, HRI/HCR. as well as the interferon-inducible, dsRNA sensitive kinase, PKR. Phosphorylation of rainbow trout and zebrafish eIF2alpha can also occur in vivo, RTG-2 and ZFL cells subjected to endoplasmic reticulum (ER) stress by treatment with the Ca2+-ionophore A23187 showed increased levels of eIF2alpha phosphorylation, suggesting similarity between the ER stress response in fish and other higher eukaryotes. Furthermore, RTG-2 cells responded to treatment with poly(I)(.)poly(C) or to infection by infectious pancreatic necrosis virus, IPNV, by increasing eIF2alpha phosphorylation. These data imply that RTG-2 cells express the interferon-induced eIF2alpha-kinase, PKR and suggests that the interferon/eIF2alpha/PKR response to virus infection may be a conserved vertebrate characteristic. Overall these data are consistent with the premise that fish are able to regulate protein synthesis in response to cellular stresses through phosphorylation of eIF2alpha. (C) 2002 Elsevier Science Ltd. All rights reserved.