Shahbazian David, Roux Philippe P, Mieulet Virginie, Cohen Michael S, Raught Brian, Taunton Jack, Hershey John W B, Blenis John, Pende Mario, Sonenberg Nahum
Department of Biochemistry, McGill Cancer Centre, McGill University, Montreal, Quebec, Canada.
EMBO J. 2006 Jun 21;25(12):2781-91. doi: 10.1038/sj.emboj.7601166. Epub 2006 Jun 8.
The eukaryotic translation initiation factor 4B (eIF4B) plays a critical role in recruiting the 40S ribosomal subunit to the mRNA. In response to insulin, eIF4B is phosphorylated on Ser422 by S6K in a rapamycin-sensitive manner. Here we demonstrate that the p90 ribosomal protein S6 kinase (RSK) phosphorylates eIF4B on the same residue. The relative contribution of the RSK and S6K modules to the phosphorylation of eIF4B is growth factor-dependent, and the two phosphorylation events exhibit very different kinetics. The S6K and RSK proteins are members of the AGC protein kinase family, and require PDK1 phosphorylation for activation. Consistent with this requirement, phosphorylation of eIF4B Ser422 is abrogated in PDK1 null embryonic stem cells. Phosphorylation of eIF4B on Ser422 by RSK and S6K is physiologically significant, as it increases the interaction of eIF4B with the eukaryotic translation initiation factor 3.
真核生物翻译起始因子4B（eIF4B）在将40S核糖体亚基募集到mRNA上起着关键作用。响应胰岛素时，eIF4B在Ser422位点被S6K以雷帕霉素敏感的方式磷酸化。在此我们证明p90核糖体蛋白S6激酶（RSK）在相同残基上磷酸化eIF4B。RSK和S6K模块对eIF4B磷酸化的相对贡献取决于生长因子，并且这两个磷酸化事件表现出非常不同的动力学。S6K和RSK蛋白是AGC蛋白激酶家族的成员，并且需要PDK1磷酸化才能激活。与此要求一致，在PDK1缺失的胚胎干细胞中，eIF4B Ser422的磷酸化被消除。RSK和S6K对eIF4B Ser422的磷酸化在生理上具有重要意义，因为它增加了eIF4B与真核生物翻译起始因子3的相互作用。
