AMPK: a cellular energy sensor primarily regulated by AMP
- 23 January 2014
- journal article
- conference paper
- Published by Portland Press Ltd. in Biochemical Society Transactions
- Vol. 42 (1), 71-75
- https://doi.org/10.1042/bst20130244
Abstract
AMPK (AMP-activated protein kinase) is a cellular energy sensor that monitors the ratio of AMP/ATP, and possibly also ADP/ATP, inside cells. Once activated by falling cellular energy levels, it acts to restore energy homoeostasis by switching on catabolic pathways that generate ATP, while switching off anabolic pathways and other processes consuming ATP. AMPK is switched on by increases in AMP via three mechanisms, all of which are antagonized by ATP: (i) promotion of phosphorylation of Thr172 by upstream activating kinases; (ii) inhibition of dephosphorylation of Thr172 by phosphatases; and (iii) allosteric activation of the phosphorylated kinase. Recently, it has been proposed that the first two mechanisms are also triggered by ADP, which might be the physiological signal rather than AMP, and that the third mechanism may not be physiologically significant. We have re-evaluated these questions, and found that only mechanism (ii) is mimicked by ADP, and that ADP is also less potent than AMP, which we still believe to be the primary signal. We have also provided evidence that mechanism (iii), i.e. allosteric activation by AMP, is a quantitatively significant mechanism in intact cells.Keywords
This publication has 46 references indexed in Scilit:
- AMP Is a True Physiological Regulator of AMP-Activated Protein Kinase by Both Allosteric Activation and Enhancing Net PhosphorylationCell Metabolism, 2013
- AMPK Is a Direct Adenylate Charge-Regulated Protein KinaseScience, 2011
- Structure of mammalian AMPK and its regulation by ADPNature, 2011
- β-Subunit myristoylation is the gatekeeper for initiating metabolic stress sensing by AMP-activated protein kinase (AMPK)Proceedings of the National Academy of Sciences of the United States of America, 2010
- Use of Cells Expressing γ Subunit Variants to Identify Diverse Mechanisms of AMPK ActivationCell Metabolism, 2010
- Calmodulin-dependent protein kinase kinase-β activates AMPK without forming a stable complex: synergistic effects of Ca2+ and AMPBiochemical Journal, 2010
- Structural basis for AMP binding to mammalian AMP-activated protein kinaseNature, 2007
- Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascadeBiochemical Journal, 2007
- 5′-AMP-Activated Protein Kinase (AMPK) Is Induced by Low-Oxygen and Glucose Deprivation Conditions Found in Solid-Tumor MicroenvironmentsMolecular and Cellular Biology, 2006
- Role of the AMP-activated protein kinase in the cellular stress responseCurrent Biology, 1994