The autophagy initiating kinase ULK1 is regulated via opposing phosphorylation by AMPK and mTOR

被引：642

作者：

Egan, Daniel F. ^{[1
,2
,3
]}

Kim, Joungmok ^{[4
,5
]}

Shaw, Reuben J. ^{[1
,2
]}

Guan, Kun-Liang ^{[4
,5
]}

机构：

[1] Univ Calif San Diego, Mol & Cell Biol Lab, Dulbecco Ctr Canc Res, La Jolla, CA 92093 USA

[2] Univ Calif San Diego, Howard Hughes Med Inst, Salk Inst Biol Studies, La Jolla, CA 92093 USA

[3] Univ Calif San Diego, Div Biol Sci, La Jolla, CA 92093 USA

[4] Univ Calif San Diego, Dept Pharmacol, La Jolla, CA 92093 USA

[5] Univ Calif San Diego, Moores Canc Ctr, La Jolla, CA 92093 USA

来源：

AUTOPHAGY | 2011年 / 7卷 / 06期

关键词：

autophagy; ULK1; AMPK; mTOR; 14-3-3;

D O I：

10.4161/auto.7.6.15123

中图分类号：

Q2 [细胞生物学];

学科分类号：

071013 [干细胞生物学];

摘要：

The serine/threonine kinase ULK1 is a mammalian homolog of Atg1, part of the Atg1 kinase complex, which is the most upstream component of the core autophagy machinery conserved from yeast to mammals. In budding yeast, activity of the Atg1 kinase complex is inhibited by TORC1 (target of rapamycin complex 1), but how the counterpart ULK1 complex in mammalian cells is regulated has been unknown. Our laboratories recently discovered that AMPK associates with, and directly phosphorylates, ULK1 on several sites and this modification is required for ULK1 activation after glucose deprivation. In contrast, when nutrients are plentiful, the mTORC1 complex phosphorylates ULK1, preventing its association and activation by AMPK. These studies have revealed a molecular mechanism of ULK1 regulation by nutrient signals via the actions of AMPK and mTORC1.

引用

页码：645 / 646

页数：2