Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine
Signaling pathways involved in translational control of protein synthesis in skeletal muscle by leucine
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DOI：
10.1093/jn/131.3.856s
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发表时间：
2001-03-01
影响因子：
4.2
通讯作者：
Jefferson, LS
中科院分区：
文献类型：
--
作者：
Anthony, JC;Anthony, TG;Jefferson, LS
许多报道证实，在骨骼肌中不可或缺的支链氨基酸亮氨酸在其启动调节翻译起始的信号转导途径的能力方面是独特的。亮氨酸的口服给药刺激与翻译阻遏物、真核起始因子（eIF）4 E结合蛋白1（4 E-BP 1）的过度磷酸化相关的蛋白质合成，导致mRNA帽结合蛋白eIF 4 E的可用性增强，用于结合eIF 4G并形成活性eIF 4F复合物。此外，亮氨酸增强70 kDa核糖体蛋白S6激酶（S6 K1）的磷酸化。这些结果表明，亮氨酸通过增强参与mRNA翻译的蛋白质的活性和合成来上调骨骼肌中的蛋白质合成。亮氨酸对翻译起始的刺激作用部分通过蛋白激酶哺乳动物雷帕霉素靶蛋白（mTOR）介导，其中胰岛素信号传导和亮氨酸信号传导会聚以促进最大反应。
Numerous reports established that in skeletal muscle the indispensable branched-chain amino acid leucine is unique in its ability to initiate signal transduction pathways that modulate translation initiation. Oral administration of leucine stimulates protein synthesis in association with hyperphosphorylation of the translational repressor, eukaryotic initiation factor (eIF) 4E binding protein 1 (4E-BP1), resulting in enhanced availability of the mRNA cap-binding protein eIF4E, for binding eIF4G and forming the active eIF4F complex. In addition, leucine enhances phosphorylation of the 70-kDa ribosomal protein S6 kinase (S6K1). These results suggest that leucine upregulates protein synthesis in skeletal muscle by enhancing both the activity and synthesis of proteins involved in mRNA translation. The stimulatory effects of leucine on translation initiation are mediated in part through the protein kinase mammalian target of rapamycin (mTOR), where both insulin signaling and leucine signaling converge to promote a maximal response.