Long-chain acyl-CoA esters inhibit phosphorylation of AMP-activated protein kinase at threonine-172 by LKB1/STRAD/MO25
| Autor: | William J Ellingson, Jeremy D Lamb, Eric B. Taylor, David G Chesser, William W. Winder |
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| Rok vydání: | 2005 |
| Předmět: |
Male
Threonine medicine.medical_specialty Physiology Endocrinology Diabetes and Metabolism Blotting Western AMP-Activated Protein Kinases Protein Serine-Threonine Kinases Rats Sprague-Dawley AMP-activated protein kinase AMP-Activated Protein Kinase Kinases Multienzyme Complexes Physiology (medical) Internal medicine medicine Animals Coenzyme A Phosphorylation Protein kinase A Beta oxidation Adaptor Proteins Signal Transducing chemistry.chemical_classification biology Chemistry Kinase AMPK Recombinant Proteins Rats Malonyl Coenzyme A Endocrinology Enzyme Phosphothreonine Biochemistry Liver biology.protein Acyl Coenzyme A Protein Kinases |
| Zdroj: | American journal of physiology. Endocrinology and metabolism. 288(6) |
| ISSN: | 0193-1849 |
| Popis: | 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. |
| Databáze: | OpenAIRE |
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