GSTDTAP  > 资源环境科学
DOI10.1038/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
ISSN2041-1723
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。
个性服务
推荐该条目
保存到收藏夹
查看访问统计
导出为Endnote文件
谷歌学术
谷歌学术中相似的文章
[Dite, Toby A.]的文章
[39;Brien, Matthew T.]的文章
百度学术
百度学术中相似的文章
[Dite, Toby A.]的文章
[39;Brien, Matthew T.]的文章
必应学术
必应学术中相似的文章
[Dite, Toby A.]的文章
[39;Brien, Matthew T.]的文章
相关权益政策
暂无数据
收藏/分享
所有评论 (0)
暂无评论
 

除非特别说明,本系统中所有内容都受版权保护,并保留所有权利。