title: AMP-activated protein kinase in metabolic control and insulin signaling.
abstract: The AMP-activated protein kinase (AMPK) system acts as a sensor of cellular energy status that is conserved in all eukaryotic cells. It is activated by increases in the cellular AMP:ATP ratio caused by metabolic stresses that either interfere with ATP production (eg, deprivation for glucose or oxygen) or that accelerate ATP consumption (eg, muscle contraction). Activation in response to increases in AMP involves phosphorylation by an upstream kinase, the tumor suppressor LKB1. In certain cells (eg, neurones, endothelial cells, and lymphocytes), AMPK can also be activated by a Ca(2+)-dependent and AMP-independent process involving phosphorylation by an alternate upstream kinase, CaMKKbeta. Once activated, AMPK switches on catabolic pathways that generate ATP, while switching off ATP-consuming processes such as biosynthesis and cell growth and proliferation. The AMPK complex contains 3 subunits, with the alpha subunit being catalytic, the beta subunit containing a glycogen-sensing domain, and the gamma subunits containing 2 regulatory sites that bind the activating and inhibitory nucleotides AMP and ATP. Although it may have evolved to respond to metabolic stress at the cellular level, hormones and cytokines such as insulin, leptin, and adiponectin can interact with the system, and it now appears to play a key role in maintaining energy balance at the whole body level. The AMPK system may be partly responsible for the health benefits of exercise and is the target for the antidiabetic drug metformin. It is a key player in the development of new treatments for obesity, type 2 diabetes, and the metabolic syndrome.
authors.affiliation: Division of Molecular Physiology, College of Life Sciences, University of Dundee, Dundee, Scotland, UK.
authors.forename: Mhairi C
authors.initials: MC
authors.lastname: Towler
authors.forename: D Grahame
authors.initials: DG
authors.lastname: Hardie
mesh_terms: D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; D000249:Adenosine Monophosphate / Q000378:metabolism*; D000255:Adenosine Triphosphate / Q000378:metabolism*; D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism; D000595:Amino Acid Sequence; D000620:Aminoimidazole Carboxamide / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D001665:Binding Sites; D002118:Calcium / Q000502:physiology; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D050260:Carbohydrate Metabolism / Q000187:drug effects / Q000502:physiology; D002453:Cell Cycle / Q000187:drug effects / Q000502:physiology; D016384:Consensus Sequence; D003920:Diabetes Mellitus / Q000188:drug therapy / Q000378:metabolism / Q000628:therapy; D004734:Energy Metabolism / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D022781:Hepatocytes / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D007004:Hypoglycemic Agents / Q000494:pharmacology / Q000627:therapeutic use; D007328:Insulin / Q000502:physiology*; D050356:Lipid Metabolism / Q000187:drug effects / Q000502:physiology; D008687:Metformin / Q000494:pharmacology / Q000627:therapeutic use; D051379:Mice; D018345:Mice, Knockout; D008958:Models, Molecular; D008969:Molecular Sequence Data; D009097:Multienzyme Complexes / Q000737:chemistry / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D032342:Muscle Cells / Q000187:drug effects / Q000378:metabolism; D009369:Neoplasms / Q000201:enzymology / Q000473:pathology; D009765:Obesity / Q000188:drug therapy / Q000378:metabolism; D010101:Oxygen Consumption / Q000187:drug effects; D036361:Peptide Hormones / Q000502:physiology; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational / Q000502:physiology; D017346:Protein Serine-Threonine Kinases / Q000737:chemistry / Q000172:deficiency / Q000187:drug effects / Q000235:genetics / Q000502:physiology*; D021122:Protein Subunits; D051381:Rats; D012265:Ribonucleotides / Q000494:pharmacology; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid
chemical_list: D007004:Hypoglycemic Agents; D007328:Insulin; D009097:Multienzyme Complexes; D036361:Peptide Hormones; D021122:Protein Subunits; D012265:Ribonucleotides; D000620:Aminoimidazole Carboxamide; D000249:Adenosine Monophosphate; D000255:Adenosine Triphosphate; D008687:Metformin; D017346:Protein Serine-Threonine Kinases; C109790:STK11 protein, human; D054737:Calcium-Calmodulin-Dependent Protein Kinase Kinase; D000091162:AMP-Activated Protein Kinase Kinases; D055372:AMP-Activated Protein Kinases; C031143:AICA ribonucleotide; D002118:Calcium