| Autor: |
Taylor, E. B., Ellingson, W. J., Lamb, J. D., Chesser, D. G., Winder, W. W. |
| Předmět: |
|
| Zdroj: |
American Journal of Physiology: Endocrinology & Metabolism; Jun2005, Vol. 288, pE1055-E1061, 7p, 9 Graphs |
| Abstrakt: |
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/STRADIMO25 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/M025 toward the peptide substrate LKB itide. 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/M025 is substrate specific and distinct from the kinase activity of LKB1/STRADIMO25 toward the peptide substrate LKB1 tide. They also demonstrate that LCACEs inhibit the AMPKK activity of LKB1/STRADIMO25 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. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
|
