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AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1

hxt_hz 添加于 2013-8-29 09:30 | 1085 次阅读 | 0 个评论

作者
Kim J, Kundu M, Viollet B, Guan K-L
摘要
Autophagy is a process by which components of the cell are degraded to maintain essential activity and viability in response to nutrient limitation. Extensive genetic studies have shown that the yeast ATG1 kinase has an essential role in autophagy induction. Furthermore, autophagy is promoted by AMP activated protein kinase (AMPK), which is a key energy sensor and regulates cellular metabolism to maintain energy homeostasis. Conversely, autophagy is inhibited by the mammalian target of rapamycin (mTOR), a central cell-growth regulator that integrates growth factor and nutrient signals. Here we demonstrate a molecular mechanism for regulation of the mammalian autophagy-initiating kinase Ulk1, a homologue of yeast ATG1. Under glucose starvation, AMPK promotes autophagy by directly activating Ulk1 through phosphorylation of Ser 317 and Ser 777. Under nutrient sufficiency, high mTOR activity prevents Ulk1 activation by phosphorylating Ulk1 Ser 757 and disrupting the interaction between Ulk1 and AMPK. This coordinated phosphorylation is important for Ulk1 in autophagy induction. Our study has revealed a signalling mechanism for Ulk1 regulation and autophagy induction in response to nutrient signalling.
详细资料
- 关键词: AMP-Activated Protein Kinases/*metabolism; Animals; Autophagy/*physiology; Glucose/metabolism; HEK293 Cells; Humans; Intracellular Signaling Peptides and Proteins/*metabolism; Mice; Phosphorylation; Protein-Serine-Threonine Kinases/genetics/*metabolism; Serine/metabolism; TOR Serine-Threonine Kinases/*metabolism
- 文献种类: Journal Article
- 期刊名称: Nature Cell Biology
- 期刊缩写: Nat Cell Biol
- 期卷页: 2011年第13卷第2期 132-141页
- 地址: Department of Pharmacology and Moores Cancer Center, University of California at San Diego, La Jolla, CA 92130, USA
- ISBN: 1465-7392
学科领域生物医药 » 基础医学
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