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AMP as a low-energy charge signal autonomously initiates assembly of AXIN-AMPK-LKB1 complex for AMPK activation.
- Source :
-
Cell metabolism [Cell Metab] 2013 Oct 01; Vol. 18 (4), pp. 546-55. - Publication Year :
- 2013
-
Abstract
- 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.<br /> (Copyright © 2013 Elsevier Inc. All rights reserved.)
- Subjects :
- AMP-Activated Protein Kinases deficiency
AMP-Activated Protein Kinases genetics
Acetyl-CoA Carboxylase metabolism
Adenosine Monophosphate metabolism
Animals
Axin Protein antagonists & inhibitors
Axin Protein genetics
Cell Line
Cell-Free System
Enzyme Activation
HEK293 Cells
Humans
Lipid Metabolism physiology
Liver cytology
Liver metabolism
Mice
Mice, Inbred BALB C
Phosphorylation drug effects
Protein Binding
RNA Interference
RNA, Small Interfering metabolism
Recombinant Proteins biosynthesis
Recombinant Proteins genetics
AMP-Activated Protein Kinases metabolism
Adenosine Monophosphate pharmacology
Axin Protein metabolism
Protein Serine-Threonine Kinases metabolism
Signal Transduction drug effects
Subjects
Details
- Language :
- English
- ISSN :
- 1932-7420
- Volume :
- 18
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Cell metabolism
- Publication Type :
- Academic Journal
- Accession number :
- 24093678
- Full Text :
- https://doi.org/10.1016/j.cmet.2013.09.005