A possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway
A possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway
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DOI：
10.1046/j.1365-2443.2003.00615.x
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发表时间：
2003-01-01
期刊：
影响因子：
2.1
通讯作者：
Yonezawa, K
中科院分区：
文献类型：
--
作者：
Kimura, N;Tokunaga, C;Yonezawa, K
背景资料：哺乳动物雷帕霉素靶蛋白（mTOR）调节多种细胞功能，包括响应营养物质（特别是氨基酸）的翻译。AMP激活的蛋白激酶（AMPK）通过对AMP.Results的改变来调节能量需求的代谢。结果：5-氨基咪唑-4-甲酰胺核糖核苷（AICAR）作为AMPK激活剂广泛应用于SV 40永生化的人角膜上皮细胞（HCE-T细胞），可抑制p70 S6 k活性。调节AMPK活性的葡萄糖可用性改变也调节p70 S6 k的活性。AICAR处理还抑制p70 S6激酶（p70 S6 k）中Thr-412的磷酸化，这对于活性是必不可少的。此外，通过在兔肺成纤维细胞系（PS120细胞）中稳定表达而过度表达突变AMPK亚基也调节p70 S6 k活性。雷帕霉素抗性p70 S6 k变体对AICAR治疗的不敏感性表明，p70 S6 k的抑制是通过一个共同的效应子介导的，支持一个模型，即mTOR及其下游效应子由AMPK.Conclusion控制：这些结果表明AMPK和mTOR信号通路可能是相连的。除了mTOR信号作为调节p70 S6 k激活的启动开关外，AMPK似乎提供了将p70 S6 k调节与细胞能量代谢联系起来的压倒性开关。
Background: The mammalian target of rapamycin (mTOR) regulates multiple cellular functions including translation in response to nutrients, especially amino acids. AMP-activated protein kinase (AMPK) modulates metabolism in response to energy demand by responding to changes in AMP.Results: The treatment of SV40-immortalized human corneal epithelial cells (HCE-T cells) with 5-aminoimidazole-4-carboxamide ribonucleoside (AICAR), widely used as an AMPK activator, inhibits p70 S6k activities. Altered glucose availability, which regulates AMPK activity, also modulates the activity of p70 S6k. AICAR treatment also inhibits phosphorylation of Thr-412 in the p70 S6 kinase (p70 S6k), which is indispensable for the activity. Furthermore, over-expression of mutant AMPK subunits by stable expression in rabbit pulmonary fibroblast cell lines (PS120 cells) also modulates p70 S6k activity. The insensitivity of the rapamycin-resistant p70 S6k variant to AICAR treatment suggests that the inhibition of p70 S6k is mediated through a common effector, supporting a model whereby mTOR and its downstream effector are controlled by AMPK.Conclusion: These results indicate that the AMPK and mTOR signalling pathways are possibly linked. In addition to the mTOR signal acting as a priming switch that modulates p70 S6k activation, AMPK appears to provide an overriding switch linking p70 S6k regulation to cellular energy metabolism.