Phosphorylation of eucaryotic translation initiation factor 4B Ser422 is modulated by S6 kinases
Phosphorylation of eucaryotic translation initiation factor 4B Ser422 is modulated by S6 kinases
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DOI：
10.1038/sj.emboj.7600193
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发表时间：
2004-04-21
期刊：
影响因子：
11.4
通讯作者：
Hershey, JWB
中科院分区：
文献类型：
--
作者：
Raught, B;Peiretti, F;Hershey, JWB
真核翻译起始因子4 B（eIF 4 B）刺激DEAD盒蛋白eIF 4A的解旋酶活性以解旋真核mRNA的50个非翻译区中的抑制性二级结构。在这里，使用磷酸肽映射和磷酸特异性抗血清，我们确定了血清响应eIF 4 B磷酸化位点，Ser 422，位于RNA结合区所需的eIF 4A解旋酶促进活性。Ser 422磷酸化似乎受S6 Ks调节：（a）Ser 422磷酸化对磷酸肌醇-3激酶的药理学抑制剂和雷帕霉素的哺乳动物靶标敏感;（B）S6 K1/S6 K2在体外特异性磷酸化Ser 422;和（c）雷帕霉素抗性S6 Ks在体内Ser 422磷酸化后赋予雷帕霉素抗性。用Ala取代Ser 422导致体内翻译测定中活性的丧失，表明该位点的磷酸化在eIF 4 B功能中起重要作用。因此，我们认为eIF 4 B可能介导了S6 Ks对翻译的一些影响。
The eucaryotic translation initiation factor 4B (eIF4B) stimulates the helicase activity of the DEAD box protein eIF4A to unwind inhibitory secondary structure in the 50 untranslated region of eucaryotic mRNAs. Here, using phosphopeptide mapping and a phosphospecific antiserum, we identify a serum-responsive eIF4B phosphorylation site, Ser422, located in an RNA-binding region required for eIF4A helicase-promoting activity. Ser422 phosphorylation appears to be regulated by the S6Ks: (a) Ser422 phosphorylation is sensitive to pharmacological inhibitors of phosphoinositide-3 kinase and the mammalian target of rapamycin; (b) S6K1/S6K2 specifically phosphorylate Ser422 in vitro; and (c) rapamycin-resistant S6Ks confer rapamycin resistance upon Ser422 phosphorylation in vivo. Substitution of Ser422 with Ala results in a loss of activity in an in vivo translation assay, indicating that phosphorylation of this site plays an important role in eIF4B function. We therefore propose that eIF4B may mediate some of the effects of the S6Ks on translation.