Interaction between the AMP-activated protein kinase and mTOR signaling pathways

Department of Cellular and Molecular Physiology, The Pennsylvania State University College of Medicine, Hershey, PA 17033, USA.
Medicine &amp Science in Sports &amp Exercise (Impact Factor: 4.46). 12/2006; 38(11):1958-64. DOI: 10.1249/01.mss.0000233796.16411.13
Source: PubMed

ABSTRACT The AMP-activated protein kinase (AMPK) has been referred to as an "energy sensor" because it binds to and is regulated by both AMP and ATP. The binding of AMP to AMPK allows it to be phosphorylated by upstream kinases, resulting in its activation. In contrast, the binding of ATP prevents its activation. AMPK regulates a multitude of metabolic processes that cumulatively function to maintain cellular energy homeostasis through repression of a number of energy-consuming processes with simultaneous enhancement of energy-producing processes. One downstream AMPK target that has been recently identified is the mammalian target of rapamycin (mTOR), a positive effector of cell growth and division. The focus of the present review is to briefly summarize current knowledge concerning the regulation of mTOR signaling by AMPK.

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    • "Previous studies suggest that metformin suppresses mTOR, a central regulator of protein synthesis and cell growth [30]. We found an increase in gene expression of mTOR in PBMCs of metformin-treated participants, which was not parallelled by an increase in mTOR protein. "
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    • "Endurance training adaptations which signal through the adenosine monophosphate-activated kinase (AMPK)/peroxisome-proliferator-activated receptor c coactivator 1a (PGC-1a) pathway (Kimball 2006) inhibit the mTOR pathway and decrease protein synthesis (Coffey et al. 2006). Cortisol and other glucocorticoids inhibit p70 S6k phosphorylation, a downstream event in mTOR signaling (Shah et al. 2000a, b, 2002). "
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    • "In contrast, AMP-dependent protein kinase (AMPK) deficient mice results in muscle hypertrophy due to enhanced mTORC1 activity (Lantier et al., 2010; Mounier et al., 2009). Since Fyn null mice have increased skeletal muscle AMPK activity, and AMPK is an established inhibitor of mTORC1-dependent signaling (Kimball, 2006; Shackelford and Shaw, 2009), we anticipated that increased Fyn expression would inhibit AMPK and thereby result in mTORC1 activation. In turn, increased Fyn expression would be expected to drive muscle hypertrophy, opposite to the observed muscle atrophy phenotype. "
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