Skeletal muscle contraction results in the phosphorylation and activation of the AMP-activated protein kinase (AMPK) by an upstream kinase, AMPKK. The LKB1-STRAD-MO25 complex is the major AMPKK in skeletal muscle; however, LKB1-STRAD-MO25 activity is not increased by muscle contraction. This relationship suggests that phosphorylation of AMPK by LKB1-STRAD-MO25 during skeletal muscle contraction may be regulated by allosteric mechanisms. In this study we tested an array of metabolites including glucose-6-phosphate (G6P), fructose-6-phosphate (F6P), fructose 1,6-bisphosphate (F1,6-P2), 3-phosphoglycerate (3PG), glucose-1-phosphate (G1P), glucose-1,6-bisphosphate (G1,6-P2), adenosine diphosphate (ADP), carnitine (Carn), acetyl-carnitine (Acarn), inosine monophosphate (IMP), inosine, and ammonia for allosteric regulation. We found that 3PG stimulated LKB1-STRAD-MO25 activity and allowed for increased AMPK phosphorylation. 3PG did not stimulate LKB1-STRAD-MO25 activity toward the peptide substrate LKB1tide. These results have identified 3PG as an AMPK-specific regulator of AMPK phosphorylation and activation by LKB1-STRAD-MO25.
College and Department
Life Sciences; Physiology and Developmental Biology
BYU ScholarsArchive Citation
Ellingson, William John, "The Effects of 3-Phosphoglycerate and Other Metabolites on the Activation of AMP-Activated Protein Kinase by LKB1/STRAD/MO25" (2006). All Theses and Dissertations. 485.
AMPK, AMPKK, metabolism, glycolysis, STK11