Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0015695 (
fatty liver
)
13,941
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
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.
...
PMID:AMP as a low-energy charge signal autonomously initiates assembly of AXIN-AMPK-LKB1 complex for AMPK activation. 2409 78
