Evidence against regulation of AMP-activated protein kinase and LKB1/STRAD/MO25 activity by creatine phosphate

Eric B Taylor; William J Ellingson; Jeremy D Lamb; David G Chesser; Cori L Compton; William W Winder

doi:10.1152/ajpendo.00313.2005

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Evidence against regulation of AMP-activated protein kinase and LKB1/STRAD/MO25 activity by creatine phosphate

Journal article

Open access

Peer reviewed

Evidence against regulation of AMP-activated protein kinase and LKB1/STRAD/MO25 activity by creatine phosphate

Eric B Taylor, William J Ellingson, Jeremy D Lamb, David G Chesser, Cori L Compton and William W Winder

American journal of physiology: endocrinology and metabolism, Vol.290(4), pp.E661-669

04/2006

DOI: 10.1152/ajpendo.00313.2005

PMID: 16278246

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Abstract

Muscle contraction results in phosphorylation and activation of the AMP-activated protein kinase (AMPK) by an AMPK kinase (AMPKK). LKB1/STRAD/MO25 (LKB1) is the major AMPKK in skeletal muscle; however, the activity of LKB1 is not increased by muscle contraction. This finding suggests that phosphorylation of AMPK by LKB1 is regulated by allosteric mechanisms. Creatine phosphate is depleted during skeletal muscle contraction to replenish ATP. Thus the concentration of creatine phosphate is an indicator of cellular energy status. A previous report found that creatine phosphate inhibits AMPK activity. The purpose of this study was to determine whether creatine phosphate would inhibit 1) phosphorylation of AMPK by LKB1 and 2) AMPK activity after phosphorylation by LKB1. We found that creatine phosphate did not inhibit phosphorylation of either recombinant or purified rat liver AMPK by LKB1. We also found that creatine phosphate did not inhibit 1) active recombinant alpha1beta1gamma1 or alpha2beta2gamma2 AMPK, 2) AMPK immunoprecipitated from rat liver extracts by either the alpha1 or alpha2 subunit, or 3) AMPK chromatographically purified from rat liver. Inhibition of skeletal muscle AMPK by creatine phosphate was greatly reduced or eliminated with increased AMPK purity. In conclusion, these results suggest that creatine phosphate is not a direct regulator of LKB1 or AMPK activity. Creatine phosphate may indirectly modulate AMPK activity by replenishing ATP at the onset of muscle contraction.

Recombinant Proteins - metabolism

Muscle, Skeletal - enzymology

Phosphorylation

Recombinant Proteins - antagonists & inhibitors

Sodium Chloride - pharmacology

Glucose-6-Phosphate - pharmacology

Sodium Acetate - pharmacology

Multienzyme Complexes - metabolism

Rats

Male

Muscle, Skeletal - metabolism

Multienzyme Complexes - antagonists & inhibitors

Rats, Sprague-Dawley

AMP-Activated Protein Kinases

Animals

Muscle Contraction - drug effects

Muscle Contraction - physiology

Muscle, Skeletal - drug effects

Protein-Serine-Threonine Kinases - antagonists & inhibitors

Phosphocreatine - pharmacology

Enzyme Activation

In Vitro Techniques

Protein-Serine-Threonine Kinases - metabolism

Details

Title: Subtitle: Evidence against regulation of AMP-activated protein kinase and LKB1/STRAD/MO25 activity by creatine phosphate
Creators: Eric B Taylor - Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah 84602, USA
William J Ellingson
Jeremy D Lamb
David G Chesser
Cori L Compton
William W Winder
Resource Type: Journal article
Publication Details: American journal of physiology: endocrinology and metabolism, Vol.290(4), pp.E661-669
DOI: 10.1152/ajpendo.00313.2005
PMID: 16278246
NLM abbreviation: Am J Physiol Endocrinol Metab
ISSN: 0193-1849
eISSN: 1522-1555
Publisher: United States
Grant note: AR-41438 / NIAMS NIH HHS
Language: English
Date published: 04/2006
Academic Unit: Molecular Physiology and Biophysics
Record Identifier: 9984025677502771

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