Ribosomal RACK1:Protein Kinase C βII Phosphorylates Eukaryotic Initiation Factor 4G1 at S1093 To Modulate Cap-Dependent and -Independent Translation Initiation
Ribosomal RACK1:Protein Kinase C βII Phosphorylates Eukaryotic Initiation Factor 4G1 at S1093 To Modulate Cap-Dependent and -Independent Translation Initiation
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DOI：
10.1128/mcb.00304-18
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发表时间：
2018-10-01
影响因子：
5.3
通讯作者：
Gromeier, Matthias
中科院分区：
文献类型：
--
作者：
Dobrikov, Mikhail I.;Dobrikova, Elena Y.;Gromeier, Matthias
真核核糖体含有高亲和力蛋白激酶C β II（PKC β II）支架、活化C激酶受体（RACK 1），但其在蛋白质合成控制中的作用仍不清楚。我们发现RACK 1：PKC β II磷酸化真核起始因子4G 1（eIF 4G 1）的S1093位和eIF 3a的S1364位。我们发现，可逆的eIF 4 G（S1093）磷酸化参与了PKC-Raf-细胞外信号调节激酶1/2（ERK 1/2）激活后的整体蛋白质合成激增，以及诱导佛波酯反应性转录物，如环氧合酶2（考克斯-2）和细胞周期蛋白依赖性激酶抑制剂（p21（Cip 1）），或参与5' 7-甲基鸟苷（m（7）G）帽非依赖性肠道病毒翻译。mRNA和蛋白质水平的比较显示，eIF 4G 1或RACK 1耗尽阻断佛波酯诱导的考克斯-2或p21 Cip 1的表达主要在翻译水平，而PKC β抑制减少他们在翻译和转录水平。我们的研究结果揭示了核糖体RACK 1在为PKC β II提供分子支架中的生理作用，以及其在协调PKC-Raf-ERK 1/2激活的翻译反应中的作用。
Eukaryotic ribosomes contain the high-affinity protein kinase C beta II (PKC beta II) scaffold, receptor for activated C kinase (RACK1), but its role in protein synthesis control remains unclear. We found that RACK1: PKC beta II phosphorylates eukaryotic initiation factor 4G1 (eIF4G1) at S1093 and eIF3a at S1364. We showed that reversible eIF4G(S1093) phosphorylation is involved in a global protein synthesis surge upon PKC-Raf-extracellular signal-regulated kinase 1/2 (ERK1/2) activation and in induction of phorbol ester-responsive transcripts, such as cyclooxygenase 2 (Cox-2) and cyclin-dependent kinase inhibitor (p21(Cip1)), or in 5' 7-methylguanosine (m(7)G) cap-independent enterovirus translation. Comparison of mRNA and protein levels revealed that eIF4G1 or RACK1 depletion blocked phorbol ester-induced Cox-2 or p21Cip1 expression mostly at the translational level, whereas PKC beta inhibition reduced them both at the translational and transcript levels. Our findings reveal a physiological role for ribosomal RACK1 in providing the molecular scaffold for PKC beta II and its role in coordinating the translational response to PKC-Raf-ERK1/2 activation.