HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) All Versions of this Article: 288/6/E1055    most recent 00516.2004v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (23) Citing Articles via Google Scholar Google Scholar Articles by Taylor, E. B. Articles by Winder, W. W. Search for Related Content PubMed PubMed Citation Articles by Taylor, E. B. Articles by Winder, W. W.

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

Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah

Submitted 28 October 2004 ; accepted in final form 4 January 2005

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.

adenosine 5'-monophosphate-activated protein kinase; adenosine 5'-monophosphate-activated protein kinase kinase; diabetes; fatty acid oxidation; STK 11

This article has been cited by other articles:

				K. Shimamura, H. Kitazawa, Y. Miyamoto, M. Kanesaka, A. Nagumo, R. Yoshimoto, K. Aragane, N. Morita, T. Ohe, T. Takahashi, et al. 5,5-Dimethyl-3-(5-methyl-3-oxo-2-phenyl-2,3-dihydro-1H-pyrazol-4-yl)-1-phenyl-3-(trifluoromethyl)-3,5,6,7-tetrahydro-1H-indole-2,4-dione, a Potent Inhibitor for Mammalian Elongase of Long-Chain Fatty Acids Family 6: Examination of Its Potential Utility as a Pharmacological Tool J. Pharmacol. Exp. Ther., July 1, 2009; 330(1): 249 - 256. [Abstract] [Full Text] [PDF]

				D. M. Thomson, S. T. Herway, N. Fillmore, H. Kim, J. D. Brown, J. R. Barrow, and W. W. Winder AMP-activated protein kinase phosphorylates transcription factors of the CREB family J Appl Physiol, February 1, 2008; 104(2): 429 - 438. [Abstract] [Full Text] [PDF]

				D. M. Thomson, J. D. Brown, N. Fillmore, B. M. Condon, H-J. Kim, J. R. Barrow, and W. W. Winder LKB1 and the regulation of malonyl-CoA and fatty acid oxidation in muscle Am J Physiol Endocrinol Metab, December 1, 2007; 293(6): E1572 - E1579. [Abstract] [Full Text] [PDF]

				C.-L. Lin, H.-C. Huang, and J.-K. Lin Theaflavins attenuate hepatic lipid accumulation through activating AMPK in human HepG2 cells J. Lipid Res., November 1, 2007; 48(11): 2334 - 2343. [Abstract] [Full Text] [PDF]

				Q. W. Shen, M. J. Zhu, J. Tong, J. Ren, and M. Du Ca2+/calmodulin-dependent protein kinase kinase is involved in AMP-activated protein kinase activation by {alpha}-lipoic acid in C2C12 myotubes Am J Physiol Cell Physiol, October 1, 2007; 293(4): C1395 - C1403. [Abstract] [Full Text] [PDF]

				T. E. Jensen, A. J. Rose, S. B. Jorgensen, N. Brandt, P. Schjerling, J. F. P. Wojtaszewski, and E. A. Richter Possible CaMKK-dependent regulation of AMPK phosphorylation and glucose uptake at the onset of mild tetanic skeletal muscle contraction Am J Physiol Endocrinol Metab, May 1, 2007; 292(5): E1308 - E1317. [Abstract] [Full Text] [PDF]

				W. J. Ellingson, D. G. Chesser, and W. W. Winder Effects of 3-phosphoglycerate and other metabolites on the activation of AMP-activated protein kinase by LKB1-STRAD-MO25 Am J Physiol Endocrinol Metab, February 1, 2007; 292(2): E400 - E407. [Abstract] [Full Text] [PDF]

				M. F. Allard, H. L. Parsons, R. Saeedi, R. B. Wambolt, and R. Brownsey AMPK and metabolic adaptation by the heart to pressure overload Am J Physiol Heart Circ Physiol, January 1, 2007; 292(1): H140 - H148. [Abstract] [Full Text] [PDF]

				M. A. Raney and L. P. Turcotte Regulation of contraction-induced FA uptake and oxidation by AMPK and ERK1/2 is intensity dependent in rodent muscle Am J Physiol Endocrinol Metab, December 1, 2006; 291(6): E1220 - E1227. [Abstract] [Full Text] [PDF]

				G. Rizki, L. Arnaboldi, B. Gabrielli, J. Yan, G. S. Lee, R. K. Ng, S. M. Turner, T. M. Badger, R. E. Pitas, and J. J. Maher Mice fed a lipogenic methionine-choline-deficient diet develop hypermetabolism coincident with hepatic suppression of SCD-1 J. Lipid Res., October 1, 2006; 47(10): 2280 - 2290. [Abstract] [Full Text] [PDF]

				M. Zang, S. Xu, K. A. Maitland-Toolan, A. Zuccollo, X. Hou, B. Jiang, M. Wierzbicki, T. J. Verbeuren, and R. A. Cohen Polyphenols Stimulate AMP-Activated Protein Kinase, Lower Lipids, and Inhibit Accelerated Atherosclerosis in Diabetic LDL Receptor-Deficient Mice. Diabetes, August 1, 2006; 55(8): 2180 - 2191. [Abstract] [Full Text] [PDF]

				S. B. Jorgensen, E. A. Richter, and J. F. P. Wojtaszewski Role of AMPK in skeletal muscle metabolic regulation and adaptation in relation to exercise J. Physiol., July 1, 2006; 574(1): 17 - 31. [Abstract] [Full Text] [PDF]

				M. J. Watt, G. R. Steinberg, Z.-P. Chen, B. E. Kemp, and M. A. Febbraio Fatty acids stimulate AMP-activated protein kinase and enhance fatty acid oxidation in L6 myotubes J. Physiol., July 1, 2006; 574(1): 139 - 147. [Abstract] [Full Text] [PDF]

				E. B. Taylor, W. J. Ellingson, J. D. Lamb, D. G. Chesser, C. L. Compton, and W. W. Winder Evidence against regulation of AMP-activated protein kinase and LKB1/STRAD/MO25 activity by creatine phosphate Am J Physiol Endocrinol Metab, April 1, 2006; 290(4): E661 - E669. [Abstract] [Full Text] [PDF]

				S. Fediuc, M. P. Gaidhu, and R. B. Ceddia Regulation of AMP-activated protein kinase and acetyl-CoA carboxylase phosphorylation by palmitate in skeletal muscle cells J. Lipid Res., February 1, 2006; 47(2): 412 - 420. [Abstract] [Full Text] [PDF]

				E. B. Taylor, J. D. Lamb, R. W. Hurst, D. G. Chesser, W. J. Ellingson, L. J. Greenwood, B. B. Porter, S. T. Herway, and W. W. Winder Endurance training increases skeletal muscle LKB1 and PGC-1{alpha} protein abundance: effects of time and intensity Am J Physiol Endocrinol Metab, December 1, 2005; 289(6): E960 - E968. [Abstract] [Full Text] [PDF]

				D. Hurst, E. B. Taylor, T. D. Cline, L. J. Greenwood, C. L. Compton, J. D. Lamb, and W. W. Winder AMP-activated protein kinase kinase activity and phosphorylation of AMP-activated protein kinase in contracting muscle of sedentary and endurance-trained rats Am J Physiol Endocrinol Metab, October 1, 2005; 289(4): E710 - E715. [Abstract] [Full Text] [PDF]