AMP as a Low-Energy Charge Signal Autonomously Initiates Assembly of AXIN-AMPK-LKB1 Complex for AMPK Activation

被引：222

作者：

Zhang, Ya-Lin ^{[1
]}

Guo, Huiling ^{[1
,2
]}

Zhang, Chen-Song ^{[1
]}

Lin, Shu-Yong ^{[1
]}

Yin, Zhenyu ^{[2
]}

Peng, Yongying ^{[1
]}

Luo, Hui ^{[1
]}

Shi, Yuzhe ^{[1
]}

Lian, Guili ^{[1
]}

Zhang, Cixiong ^{[1
]}

Li, Mengqi ^{[1
]}

Ye, Zhiyun ^{[1
]}

Ye, Jing ^{[3
]}

Han, Jiahuai ^{[1
]}

Li, Peng ^{[4
]}

Wu, Jia-Wei ^{[4
]}

Lin, Sheng-Cai ^{[1
]}

机构：

[1] Xiamen Univ, Sch Life Sci, State Key Lab Cellular Stress Biol, Xiamen 361102, Fujian, Peoples R China

[2] Xiamen Univ, Zhongshan Hosp, Dept Hepatobiliary Surg, Xiamen 361004, Fujian, Peoples R China

[3] Xijing Hosp, Dept Pathol, Xian 710032, Shaanxi, Peoples R China

[4] Tsinghua Univ, Sch Life Sci, Beijing 100101, Peoples R China

来源：

CELL METABOLISM | 2013年 / 18卷 / 04期

基金：

中国国家自然科学基金;

关键词：

DEPENDENT PROTEIN-KINASE; HEPATIC STEATOSIS; UPSTREAM KINASE; ALPHA-SUBUNITS; RAT-LIVER; LKB1; BETA; AXIN; CELL; PHOSPHORYLATION;

D O I：

10.1016/j.cmet.2013.09.005

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

The AMP-activated protein kinase (AMPK) is a master regulator of metabolic homeostasis by sensing cellular energy status. AMPK is mainly activated via phosphorylation by LKB1 when cellular AMP/ADP levels are increased. However, how AMP/ADP brings about AMPK phosphorylation remains unclear. Here, we show that it is AMP, but not ADP, that drives AXIN to directly tether LKB1 to phosphorylate AMPK. The complex formation of AXIN-AMPK-LKB1 is greatly enhanced in glucose-starved or AICAR-treated cells and in cell-free systems supplemented with exogenous AMP. Depletion of AXIN abrogated starvation-induced AMPK-LKB1 colocalization. Importantly, adenovirus-based knockdown of AXIN in the mouse liver impaired AMPK activation and caused exacerbated fatty liver after starvation, underscoring an essential role of AXIN in AMPK activation. These findings demonstrate an initiating role of AMP and demonstrate that AXIN directly transmits AMP binding of AMPK to its activation by LKB1, uncovering the mechanistic route for AMP to elicit AMPK activation by LKB1.

引用

页码：546 / 555

页数：10

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