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DOI | 10.1038/s41467-018-06233-x |
The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs | |
Dite, Toby A.1; 39;Brien, Matthew T.2 | |
2017-09-18 | |
发表期刊 | NATURE COMMUNICATIONS
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ISSN | 2041-1723 |
出版年 | 2017 |
卷号 | 8 |
文章类型 | Article |
语种 | 英语 |
国家 | Australia; USA; France; Canada; Scotland; Switzerland |
英文摘要 | AMP-activated protein kinase (AMPK) is a metabolic stress-sensing enzyme responsible for maintaining cellular energy homeostasis. Activation of AMPK by salicylate and the thienopyridone A-769662 is critically dependent on phosphorylation of Ser108 in the beta 1 regulatory subunit. Here, we show a possible role for Ser108 phosphorylation in cell cycle regulation and promotion of pro-survival pathways in response to energy stress. We identify the autophagy initiator Unc-51-like kinase 1 (ULK1) as a beta 1-Ser108 kinase in cells. Cellular beta 1-Ser108 phosphorylation by ULK1 was dependent on AMPK beta-subunit myristoylation, metabolic stress associated with elevated AMP/ATP ratio, and the intrinsic energy sensing capacity of AMPK; features consistent with an AMP-induced myristoyl switch mechanism. We further demonstrate cellular AMPK signaling independent of activation loop Thr172 phosphorylation, providing potential insight into physiological roles for Ser108 phosphorylation. These findings uncover new mechanisms by which AMPK could potentially maintain cellular energy homeostasis independently of Thr172 phosphorylation. |
领域 | 资源环境 |
收录类别 | SCI-E |
WOS记录号 | WOS:000411024900007 |
WOS关键词 | ACTIVATED PROTEIN-KINASE ; SKELETAL-MUSCLE ; STRUCTURAL BASIS ; GLUCOSE-UPTAKE ; PHOSPHORYLATION ; INHIBITION ; OXIDATION ; ENERGY ; IDENTIFICATION ; LIPOGENESIS |
WOS类目 | Multidisciplinary Sciences |
WOS研究方向 | Science & Technology - Other Topics |
URL | 查看原文 |
引用统计 | |
文献类型 | 期刊论文 |
条目标识符 | http://119.78.100.173/C666/handle/2XK7JSWQ/203998 |
专题 | 资源环境科学 |
作者单位 | 1.Univ Melbourne, St Vincents Inst Med Res, Metab Signalling Lab, Melbourne, Vic, Australia; 2.Univ Melbourne, St Vincents Inst Med Res, Prot Chem & Metab, Melbourne, Vic, Australia; 3.Australian Catholic Univ, Mary MacKillop Inst Hlth Res, Melbourne, Vic, Australia; 4.Univ Sydney, Sch Mol Biosci, Charles Perkins Ctr, Sydney, NSW, Australia; 5.St Jude Childrens Res Hosp, Dept Pathol, 332 N Lauderdale St, Memphis, TN 38105 USA; 6.INSERM, Inst Cochin, U1016, Paris, France; 7.CNRS, UMR8104, Paris, France; 8.Univ Paris 05, Sorbonne Paris Cite, Paris, France; 9.McMaster Univ, Dept Med, Div Endocrinol, Hamilton, ON, Canada; 10.McMaster Univ, Dept Med, Div Metab, Hamilton, ON, Canada; 11.McMaster Univ, Dept Biochem & Biomed Sci, Hamilton, ON, Canada; 12.Univ Dundee, Sch Life Sci, MRC, Prot Phosphorylat & Ubiquitylat Unit, Dundee, Scotland; 13.Nestle Inst Hlth Sci SA, Lausanne, Switzerland |
推荐引用方式 GB/T 7714 | Dite, Toby A.,39;Brien, Matthew T.. The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs[J]. NATURE COMMUNICATIONS,2017,8. |
APA | Dite, Toby A.,&39;Brien, Matthew T..(2017).The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs.NATURE COMMUNICATIONS,8. |
MLA | Dite, Toby A.,et al."The autophagy initiator ULK1 sensitizes AMPK to allosteric drugs".NATURE COMMUNICATIONS 8(2017). |
条目包含的文件 | 条目无相关文件。 |
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