Long-chain acyl-CoA esters inhibit phosphorylation of AMP-activated protein kinase at threonine-172 by LKB1/STRAD/MO25

E B Taylor; W J Ellingson; J D Lamb; D G Chesser; W W Winder

doi:10.1152/ajpendo.00516.2004

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Long-chain acyl-CoA esters inhibit phosphorylation of AMP-activated protein kinase at threonine-172 by LKB1/STRAD/MO25

Journal article

Peer reviewed

Long-chain acyl-CoA esters inhibit phosphorylation of AMP-activated protein kinase at threonine-172 by LKB1/STRAD/MO25

E B Taylor, W J Ellingson, J D Lamb, D G Chesser and W W Winder

American journal of physiology: endocrinology and metabolism, Vol.288(6), pp.E1055-1061

06/2005

DOI: 10.1152/ajpendo.00516.2004

PMID: 15644453

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Abstract

Activation of the AMP-activated protein kinase (AMPK) results in acute changes in cellular metabolism and transcriptional events that make the cell more robust when encountering an energy challenge. AMPK is thought to be inhibited by glycogen, the major storage form of intracellular carbohydrate. We hypothesized that long-chain acyl-CoA esters (LCACEs) might also inhibit AMPK signaling. Cytosolic LCACEs are available for immediate transport and oxidation within the mitochondria and accordingly may be representative of the lipid energy charge of the cell. We found that LCACEs inhibited phosphorylation of AMPK by the recombinant AMPK kinase (AMPKK) LKB1/STRAD/MO25 in a concentration-dependent manner. Palmitoyl-CoA (PCoA) did not affect the activity of phosphothreonine-172 AMPK. PCoA potently inhibited AMPKK purified from liver. Conversely, PCoA stimulated the kinase activity of LKB1/STRAD/MO25 toward the peptide substrate LKB1tide. Octanoyl-CoA, palmitate, and palmitoylcarnitine did not inhibit AMPKK activity. Removal of AMP from the reaction mixture resulted in reduced AMPKK activity in the presence of PCoA. In conclusion, these results demonstrate that the AMPKK activity of LKB1/STRAD/MO25 is substrate specific and distinct from the kinase activity of LKB1/STRAD/MO25 toward the peptide substrate LKB1tide. They also demonstrate that LCACEs inhibit the AMPKK activity of LKB1/STRAD/MO25 in a specific manner with a dependence on both a long fatty chain and a CoA moiety. These results suggest that the AMPK signaling cascade may directly sense and respond to the lipid energy charge of the cell.

Protein Kinases - metabolism

Recombinant Proteins - metabolism

Malonyl Coenzyme A - pharmacology

Liver - metabolism

Multienzyme Complexes - metabolism

Rats

Male

Coenzyme A - pharmacology

Acyl Coenzyme A - pharmacology

Multienzyme Complexes - antagonists & inhibitors

Threonine - metabolism

Rats, Sprague-Dawley

AMP-Activated Protein Kinases

Blotting, Western

Phosphothreonine - metabolism

Animals

Protein-Serine-Threonine Kinases - antagonists & inhibitors

Phosphorylation - drug effects

Adaptor Proteins, Signal Transducing - metabolism

Protein-Serine-Threonine Kinases - metabolism

Details

Title: Subtitle: Long-chain acyl-CoA esters inhibit phosphorylation of AMP-activated protein kinase at threonine-172 by LKB1/STRAD/MO25
Creators: E B Taylor - Department of Physiology and Developmental Biology, Brigham Young Univ., Provo, Utah 84602, USA
W J Ellingson
J D Lamb
D G Chesser
W W Winder
Resource Type: Journal article
Publication Details: American journal of physiology: endocrinology and metabolism, Vol.288(6), pp.E1055-1061
Publisher: United States
DOI: 10.1152/ajpendo.00516.2004
PMID: 15644453
ISSN: 0193-1849
eISSN: 1522-1555
Language: English
Date published: 06/2005
Academic Unit: Molecular Physiology and Biophysics; Fraternal Order of Eagles Diabetes Research Center
Record Identifier: 9984025429402771

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