| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
|
|
|
|||||||
|
|||||||||
| ||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||||
Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah
Submitted 21 August 2007 ; accepted in final form 27 November 2007
AMP-activated protein kinase (AMPK) has been identified as a regulator of gene transcription, increasing mitochondrial proteins of oxidative metabolism as well as hexokinase expression in skeletal muscle. In mice, muscle-specific knockout of LKB1, a component of the upstream kinase of AMPK, prevents contraction- and 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside (AICAR)-induced activation of AMPK in skeletal muscle, and the increase in hexokinase II protein that is normally observed with chronic AICAR activation of AMPK. Since previous reports show a cAMP response element in the promoter region of the hexokinase II gene, we hypothesized that the cAMP-response element (CRE) binding protein (CREB) family of transcription factors could be targets of AMPK. Using radioisotopic kinase assays, we found that recombinant and rat liver and muscle AMPK phosphorylated CREB1 at the same site as cAMP-dependent protein kinase (PKA). AMPK was also found to phosphorylate activating transcription factor 1 (ATF1), CRE modulator (CREM), and CREB-like 2 (CREBL2), but not ATF2. Treatment of HEK-293 cells stably transfected with a CREB-driven luciferase reporter with AICAR increased luciferase activity approximately threefold over a 24-h time course. This increase was blocked with compound C, an AMPK inhibitor. In addition, AICAR-induced activation of AMPK in incubated rat epitrochlearis muscles resulted in an increase in both phospho-acetyl-CoA carboxylase and phospho-CREB. We conclude that CREB and related proteins are direct downstream targets for AMPK and are therefore likely involved in mediating some effects of AMPK on expression of genes having a CRE in their promoters.
activating transcription factor 1; adenosine 5'-cyclic monophosphate-responsive element modulator; LKB1; transcription control
This article has been cited by other articles:
|
|
 |
|
  M. R. Hayes, K. P. Skibicka, K. K. Bence, and H. J. Grill Dorsal Hindbrain 5'-Adenosine Monophosphate-Activated Protein Kinase as an Intracellular Mediator of Energy Balance Endocrinology, May 1, 2009; 150(5): 2175 - 2182. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D.M. Thomson, J.D. Brown, N. Fillmore, S.K. Ellsworth, D. L. Jacobs, W.W. Winder, C.A. Fick, and S.E. Gordon AMP-activated protein kinase response to contractions and treatment with the AMPK activator AICAR in young adult and old skeletal muscle J. Physiol., May 1, 2009; 587(9): 2077 - 2086. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. R Almon, D. C DuBois, W. Lai, B. Xue, J. Nie, and W. J Jusko Gene expression analysis of hepatic roles in cause and development of diabetes in Goto-Kakizaki rats J. Endocrinol., March 1, 2009; 200(3): 331 - 346. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Sag, D. Carling, R. D. Stout, and J. Suttles Adenosine 5'-Monophosphate-Activated Protein Kinase Promotes Macrophage Polarization to an Anti-Inflammatory Functional Phenotype J. Immunol., December 15, 2008; 181(12): 8633 - 8641. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. J. Branvold, D. R. Allred, D. J. Beckstead, H. J. Kim, N. Fillmore, B. M. Condon, J. D. Brown, S. N. Sudweeks, D. M. Thomson, and W. W. Winder Thyroid hormone effects on LKB1, MO25, phospho-AMPK, phospho-CREB, and PGC-1{alpha} in rat muscle J Appl Physiol, October 1, 2008; 105(4): 1218 - 1227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Y. C. Long and J. R. Zierath Influence of AMP-activated protein kinase and calcineurin on metabolic networks in skeletal muscle Am J Physiol Endocrinol Metab, September 1, 2008; 295(3): E545 - E552. [Abstract] [Full Text] [PDF]
|
|
| HOME | HELP | FEEDBACK | SUBSCRIPTIONS | ARCHIVE | SEARCH | TABLE OF CONTENTS |
| Visit Other APS Journals Online |
