Ellingson W J, Chesser D G, Winder W W
Department of Physiology and Developmental Biology, Brigham Young University, Provo, Utah 84602, USA.
Am J Physiol Endocrinol Metab. 2007 Feb;292(2):E400-7. doi: 10.1152/ajpendo.00322.2006. Epub 2006 Sep 19.
Skeletal muscle contraction results in the phosphorylation and activation of the AMP-activated protein kinase (AMPK) by an upstream kinase (AMPKK). The LKB1-STE-related adaptor (STRAD)-mouse protein 25 (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, fructose 6-phosphate, fructose 1,6-bisphosphate, 3-phosphoglycerate (3-PG), glucose 1-phosphate, glucose 1,6-bisphosphate, ADP, carnitine, acetylcarnitine, IMP, inosine, and ammonia for allosteric regulation. ADP inhibited both AMPK and LKB1-STRAD-MO25 actions, but probably is not important physiologically because of the low free ADP inside the muscle fiber. We found that 3-PG stimulated LKB1-STRAD-MO25 activity and allowed for increased AMPK phosphorylation. 3-PG did not stimulate LKB1-STRAD-MO25 activity toward the peptide substrate LKB1tide. These results have identified 3-PG as an AMPK-specific regulator of AMPK phosphorylation and activation by LKB1-STRAD-MO25.
骨骼肌收缩导致上游激酶（AMPKK）对AMP激活的蛋白激酶（AMPK）进行磷酸化并激活。LKB1-STE相关衔接蛋白（STRAD）-小鼠蛋白25（MO25）复合物是骨骼肌中的主要AMPKK；然而，肌肉收缩并不会增加LKB1-STRAD-MO25的活性。这种关系表明，在骨骼肌收缩过程中，LKB1-STRAD-MO25对AMPK的磷酸化可能受变构机制调控。在本研究中，我们测试了一系列代谢物，包括6-磷酸葡萄糖、6-磷酸果糖、1,6-二磷酸果糖、3-磷酸甘油酸（3-PG）、1-磷酸葡萄糖、1,6-二磷酸葡萄糖、ADP、肉碱、乙酰肉碱、肌苷酸、肌苷和氨，以研究其变构调节作用。ADP抑制AMPK和LKB1-STRAD-MO25的活性，但由于肌纤维内游离ADP含量较低，其在生理上可能并不重要。我们发现3-PG刺激LKB1-STRAD-MO25的活性，并使AMPK磷酸化增加。3-PG不会刺激LKB1-STRAD-MO25对肽底物LKB1tide的活性。这些结果已确定3-PG是LKB1-STRAD-MO25对AMPK进行磷酸化和激活的特异性调节因子。
