AMP-activated protein kinase: new regulation, new roles?

Boyer, 1977, Oxidative phosphorylation and photophosphorylation, Annu. Rev. Biochem., 46, 955, 10.1146/annurev.bi.46.070177.004515

Hardie, 2011, AMP-activated protein kinase: also regulated by ADP?, Trends Biochem. Sci., 36, 470, 10.1016/j.tibs.2011.06.004

Kahn, 2005, AMP-activated protein kinase: ancient energy gauge provides clues to modern understanding of metabolism, Cell Metab., 1, 15, 10.1016/j.cmet.2004.12.003

Lage, 2008, AMPK: a metabolic gauge regulating whole-body energy homeostasis, Trends Mol. Med., 14, 539, 10.1016/j.molmed.2008.09.007

Shackelford, 2009, The LKB1–AMPK pathway: metabolism and growth control in tumour suppression, Nat. Rev. Cancer, 9, 563, 10.1038/nrc2676

Steinberg, 2009, AMPK in health and disease, Physiol. Rev., 89, 1025, 10.1152/physrev.00011.2008

Viollet, 2010, AMPK inhibition in health and disease, Crit. Rev. Biochem. Mol. Biol., 45, 276, 10.3109/10409238.2010.488215

Zhang, 2009, AMPK: an emerging drug target for diabetes and the metabolic syndrome, Cell Metab., 9, 407, 10.1016/j.cmet.2009.03.012

Carling, 2004, The AMP-activated protein kinase cascade: a unifying system for energy control, Trends Biochem. Sci., 29, 18, 10.1016/j.tibs.2003.11.005

Hudson, 2003, A novel domain in AMP-activated protein kinase causes glycogen storage bodies similar to those seen in hereditary cardiac arrhythmias, Curr. Biol., 13, 861, 10.1016/S0960-9822(03)00249-5

Polekhina, 2003, AMPKβ subunit targets metabolic stress sensing to glycogen, Curr. Biol., 13, 867, 10.1016/S0960-9822(03)00292-6

Woods, 1996, Characterization of AMP-activated protein kinase β and γ subunits. Assembly of the heterotrimeric complex in vitro, J. Biol. Chem., 271, 10282, 10.1074/jbc.271.17.10282

Bateman, 1997, The structure of a domain common to archaebacteria and the homocystinuria disease protein, Trends Biochem. Sci., 22, 12, 10.1016/S0968-0004(96)30046-7

Kemp, 2004, Bateman domains and adenosine derivatives form a binding contract, J. Clin. Invest., 113, 182, 10.1172/JCI200420846

Carlson, 1999, Glucose repression in yeast, Curr. Opin. Microbiol., 2, 202, 10.1016/S1369-5274(99)80035-6

Gancedo, 1998, Yeast carbon catabolite repression, Microbiol. Mol. Biol. Rev., 62, 334, 10.1128/MMBR.62.2.334-361.1998

Wilson, 1996, Glucose repression/derepression in budding yeast: SNF1 protein kinase is activated by phosphorylation under derepressing conditions, and this correlates with a high AMP:ATP ratio, Curr. Biol., 6, 1426, 10.1016/S0960-9822(96)00747-6

Woods, 1994, Yeast SNF1 is functionally related to mammalian AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo, J. Biol. Chem., 269, 19509, 10.1016/S0021-9258(17)32198-1

Carling, 1989, Purification and characterisation of the AMP-activated protein kinase, Eur. J. Biochem., 186, 129, 10.1111/j.1432-1033.1989.tb15186.x

Corton, 1995, 5-Aminoimidazole-4-carboxamide ribonucleoside: a specific method for activating AMP-activated protein kinase in intact cells, Eur. J. Biochem., 229, 55800565, 10.1111/j.1432-1033.1995.tb20498.x

Sullivan, 1994, Characterization of 5′-AMP-activated protein kinase in human liver using specific peptide substrates and the effects of 5′-AMP analogs on enzyme activity, Biochem. Biophys. Res. Commun., 200, 1551, 10.1006/bbrc.1994.1627

Cheung, 2000, Characterization of AMP-activated protein kinase γ subunit isoforms and their role in AMP binding, Biochem. J., 346, 659, 10.1042/bj3460659

Hawley, 1996, Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase, J. Biol. Chem., 271, 27879, 10.1074/jbc.271.44.27879

Neumann, 2003, Mammalian AMP-activated protein kinase: functional, heterotrimeric complexes by co-expression of subunits in Escherichia coli, Protein Expr. Purif., 30, 230, 10.1016/S1046-5928(03)00126-8

Carling, 2008, The regulation of AMP-activated protein kinase by upstream kinases, Int. J. Obesity, 32, S55, 10.1038/ijo.2008.124

Hawley, 2005, Calmodulin-dependent protein kinase kinase β is an alternative upstream kinase for AMP-activated protein kinase, Cell Metab., 2, 9, 10.1016/j.cmet.2005.05.009

Woods, 2005, Ca2+/calmodulin-dependent protein kinase kinase β acts upstream of AMP-activated protein kinase in mammalian cells, Cell Metab., 2, 21, 10.1016/j.cmet.2005.06.005

Hawley, 2003, Complexes between the LKB1 tumor suppressor, STRAD α/β and MO25 α/β are upstream kinases in the AMP-activated protein kinase cascade, J. Biol., 2, 28, 10.1186/1475-4924-2-28

Woods, 2003, LKB1 is the upstream kinase in the AMP-activated protein kinase cascade, Curr. Biol., 13, 2004, 10.1016/j.cub.2003.10.031

Cool, 2006, Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome, Cell Metab., 3, 403, 10.1016/j.cmet.2006.05.005

Sanders, 2007, Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family, J. Biol. Chem., 282, 32539, 10.1074/jbc.M706543200

Davies, 1995, 5′-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2Cα and native bovine protein phosphatase-2AC, FEBS Lett., 377, 421, 10.1016/0014-5793(95)01368-7

Haystead, 1989, Effects of the tumour promoter okadaic acid on intracellular protein phosphorylation and metabolism, Nature, 337, 78, 10.1038/337078a0

Moore, 1991, Evidence that AMP triggers phosphorylation as well as direct allosteric activation of rat liver AMP-activated protein kinase. A sensitive mechanism to protect the cell against ATP depletion, Eur. J. Biochem., 199, 691, 10.1111/j.1432-1033.1991.tb16172.x

Voss, 2011, Ppm1E is an in cellulo AMP-activated protein kinase phosphatase, Cell. Signalling, 23, 114, 10.1016/j.cellsig.2010.08.010

Garcia-Haro, 2010, The PP1-R6 protein phosphatase holoenzyme is involved in the glucose-induced dephosphorylation and inactivation of AMP-activated protein kinase, a key regulator of insulin secretion, in MIN6 cells, FASEB J., 24, 5080

Tokumitsu, 1996, Requirements for calcium and calmodulin in the calmodulin kinase activation cascade, J. Biol. Chem., 271, 5617, 10.1074/jbc.271.10.5617

Stahmann, 2006, Thrombin activates AMP-activated protein kinase in endothelial cells via a pathway involving Ca2+/calmodulin-dependent protein kinase kinase β, Mol. Cell. Biol., 26, 5933, 10.1128/MCB.00383-06

Tamas, 2006, Regulation of the energy sensor AMP-activated protein kinase by antigen receptor and Ca2+ in T lymphocytes, J. Exp. Med., 203, 1665, 10.1084/jem.20052469

Thornton, 2008, Muscarinic receptor activation of AMP-activated protein kinase inhibits orexigenic neuropeptide mRNA expression, J. Biol. Chem., 283, 17116, 10.1074/jbc.M708987200

Sakamoto, 2004, Activity of LKB1 and AMPK-related kinases in skeletal muscle: effects of contraction, phenformin, and AICAR, Am. J. Physiol. Endocrinol. Metab., 287, E310, 10.1152/ajpendo.00074.2004

Hawley, 1995, 5′-AMP activates the AMP-activated protein kinase cascade and Ca2+/calmodulin activates the calmodulin-dependent protein kinase-I cascade, via 3 independent mechanisms, J. Biol. Chem., 270, 27186, 10.1074/jbc.270.45.27186

Sanders, 2007, Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade, Biochem. J., 403, 139, 10.1042/BJ20061520

Oakhill, 2010, Beta subunit myristoylation is the gatekeeper for initaiting metabolic stress sensing by AMP-activated protein kinase (AMPK), Proc. Natl. Acad. Sci. U.S.A., 107, 19237, 10.1073/pnas.1009705107

Mitchelhill, 1997, Posttranslational modifications of the 5′-AMP-activated protein kinase β1 subunit, J. Biol. Chem., 272, 24475, 10.1074/jbc.272.39.24475

Suter, 2006, Dissecting the role of AMP for allosteric stimulation, activation and deactivation of AMP-activated protein kinase, J. Biol. Chem., 281, 32207, 10.1074/jbc.M606357200

Xiao, 2011, Structure of mammalian AMPK and its regulation by ADP, Nature, 472, 230, 10.1038/nature09932

Oakhill, 2011, AMPK is a direct adenylate charge-regulated protein kinase, Science, 332, 1433, 10.1126/science.1200094

Mayer, 2011, ADP regulates SNF1, the Saccharomyces cerevisiae homologue of AMP-activated protein kinase, Cell Metab., 14, 707, 10.1016/j.cmet.2011.09.009

Mitchelhill, 1994, Mammalian AMP-activated protein kinase shares structural and functional homology with the catalytic domain of yeast Snf1 protein kinase, J. Biol. Chem., 269, 2361, 10.1016/S0021-9258(17)41951-X

Xiao, 2007, Structural basis for AMP binding to mammalian AMP-activated protein kinase, Nature, 449, 496, 10.1038/nature06161

Scott, 2004, CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations, J. Clin. Invest., 113, 274, 10.1172/JCI19874

Kemp, 2007, AMPK structure and regulation from three angles, Structure, 15, 1161, 10.1016/j.str.2007.09.006

Carling, 2011, AMP-activated protein kinase: nature's energy sensor, Nat. Chem. Biol., 7, 512, 10.1038/nchembio.610

Goransson, 2007, Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase, J. Biol. Chem., 282, 32549, 10.1074/jbc.M706536200

Pang, 2007, Conserved α-helix acts as an autoinhibitory sequence in AMP-activated protein kinase a subunits, J. Biol. Chem., 282, 495, 10.1074/jbc.M605790200

Chen, 2009, Structural insight into the autoinhibition mechanism of AMP-activated protein kinase, Nature, 459, 1146, 10.1038/nature08075

Corkey, 1986, Regulation of free and bound magnesium in rat hepatocytes and isolated mitochondria, J. Biol. Chem., 261, 2567, 10.1016/S0021-9258(17)35825-8

Tsou, 2011, A fluorescent reporter of AMPK activity and cellular energy stress, Cell Metab., 13, 476, 10.1016/j.cmet.2011.03.006

Imamura, 2009, Visualization of ATP levels inside single living cells with fluorescence resonance energy transfer-based genetically encoded indicators, Proc. Natl. Acad. Sci. U.S.A., 106, 15651, 10.1073/pnas.0904764106

Bendayan, 2009, Association of AMP-activated protein kinase subunits with glycogen particles as revealed in situ by immunoelectron microscopy, J. Histochem. Cytochem., 57, 963, 10.1369/jhc.2009.954016

McBride, 2009, The glycogen-binding domain on the AMPK β subunit allows the kinase to act as a glycogen sensor, Cell Metab., 9, 23, 10.1016/j.cmet.2008.11.008

Bieri, 2012, AMP-activated protein kinase β-subunit requires internal motion for optimal carbohydrate binding, Biophys. J., 102, 305, 10.1016/j.bpj.2011.12.012

Lin, 2012, Functional dissection of lysine deacetylases reveals that HDAC1 and p300 regulate AMPK, Nature, 482, 251, 10.1038/nature10804

Salt, 1998, AMP-activated protein kinase: greater AMP dependence, and preferential nuclear localization, of complexes containing the α2 isoform, Biochem. J., 334, 177, 10.1042/bj3340177

Kroemer, 2010, Autophagy and the integrated stress response, Mol. Cell, 40, 280, 10.1016/j.molcel.2010.09.023

Hara, 2008, FIP200, a ULK-interacting protein, is required for autophagosome formation in mammalian cells, J. Cell Biol., 181, 497, 10.1083/jcb.200712064

Hosokawa, 2009, Atg101, a novel mammalian autophagy protein interacting with Atg13, Autophagy, 5, 973, 10.4161/auto.5.7.9296

Hosokawa, 2009, Nutrient-dependent mTORC1 association with the ULK1–Atg13–FIP200 complex required for autophagy, Mol. Biol. Cell, 20, 1981, 10.1091/mbc.e08-12-1248

Shang, 2011, Nutrient starvation elicits an acute autophagic response mediated by Ulk1 dephosphorylation and its subsequent dissociation from AMPK, Proc. Natl. Acad. Sci. U.S.A., 108, 4788, 10.1073/pnas.1100844108

Egan, 2011, Phosphorylation of ULK1 (hATG1) by AMP-activated protein kinase connects energy sensing to mitophagy, Science, 331, 456, 10.1126/science.1196371

Kim, 2011, AMPK and mTOR regulate autophagy through direct phosphorylation of Ulk1, Nat. Cell Biol., 13, 132, 10.1038/ncb2152

Grumati, 2011, Physical exercise stimulates autophagy in normal skeletal muscles but is detrimental for collagen VI deficient muscles, Autophagy, 7, 1415, 10.4161/auto.7.12.17877

He, 2012, Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis, Nature, 481, 511, 10.1038/nature10758

Hoyer-Hansen, 2007, Control of macroautophagy by calcium, calmodulin-dependent kinase kinase-β, and Bcl-2, Mol. Cell, 25, 193, 10.1016/j.molcel.2006.12.009

Hotamisligil, 1993, Adipose expression of tumor necrosis factor α: direct role in obesity-linked insulin resistance, Science, 259, 87, 10.1126/science.7678183

Nath, 2005, 5-Aminoimidazole-4-carboxamide ribonucleoside: a novel immunomodulator with therapeutic efficacy in experimental autoimmune encephalomyelitis, J. Immunol., 175, 566, 10.4049/jimmunol.175.1.566

Bai, 2010, AMPK agonist downregulates innate and adaptive immune responses in TNBS-induced murine acute and relapsing colitis, Biochem. Pharmacol., 80, 1708, 10.1016/j.bcp.2010.08.009

Jhun, 2004, 5-Aminoimidazole-4-carboxamide riboside suppresses lipopolysaccharide-induced TNF-α production through inhibition of phosphatidylinositol 3-kinase/Akt activation in RAW 264.7 murine macrophages, Biochem. Biophys. Res. Commun., 318, 372, 10.1016/j.bbrc.2004.04.035

Kuo, 2008, Inhibition of lipopolysaccharide-induced inducible nitric oxide synthase and cyclooxygenase-2 gene expression by 5-aminoimidazole-4-carboxamide riboside is independent of AMP-activated protein kinase, J. Cell. Biochem., 103, 931, 10.1002/jcb.21466

Sag, 2008, Adenosine 5′-monophosphate-activated protein kinase promotes macrophage polarization to an anti-inflammatory functional phenotype, J. Immunol., 181, 8633, 10.4049/jimmunol.181.12.8633

Yang, 2010, Macrophage α1 AMP-activated protein kinase (α1AMPK) antagonizes fatty acid-induced inflammation through SIRT1, J. Biol. Chem., 285, 19051, 10.1074/jbc.M110.123620

Galic, 2011, Hematopoietic AMPKβ1 reduces mouse adipose tissue macrophage inflammation and insulin resistance in obesity, J. Clin. Invest., 121, 4903, 10.1172/JCI58577

Buler, 2012, Energy sensing factors coactivator PGC-1α and AMP-activated protein kinase control expression of inflammatory mediators in liver: induction of Interleukin 1 receptor antagonist, J. Biol. Chem., 287, 1847, 10.1074/jbc.M111.302356

Isoda, 2006, Metformin inhibits proinflammatory responses and nuclear factor-κB in human vascular wall cells, Arterioscler. Thromb. Vasc. Biol., 26, 611, 10.1161/01.ATV.0000201938.78044.75

Vieira, 2009, Effects of exercise and low-fat diet on adipose tissue inflammation and metabolic complications in obese mice, Am. J. Physiol. Endocrinol. Metab., 296, E1164, 10.1152/ajpendo.00054.2009

Newman, 1990, Phagocytosis of Histoplasma capsulatum yeasts and microconidia by human cultured macrophages and alveolar macrophages. Cellular cytoskeleton requirement for attachment and ingestion, J. Clin. Invest., 85, 223, 10.1172/JCI114416

Caron, 1998, Identification of two distinct mechanisms of phagocytosis controlled by different Rho GTPases, Science, 282, 1717, 10.1126/science.282.5394.1717

Bae, 2011, AMP-activated protein kinase enhances the phagocytic ability of macrophages and neutrophils, FASEB J., 25, 4358, 10.1096/fj.11-190587

Nakano, 2010, AMPK controls the speed of microtubule polymerization and directional cell migration through CLIP-170 phosphorylation, Nat. Cell Biol., 12, 583, 10.1038/ncb2060

Chopra, 2011, Cellular energy depletion resets whole-body energy by promoting coactivator-mediated dietary fuel absorption, Cell Metab., 13, 35, 10.1016/j.cmet.2010.12.001

Fu, 2010, Regulation of bile canalicular network formation and maintenance by AMP-activated protein kinase and LKB1, J. Cell Sci., 123, 3294, 10.1242/jcs.068098

Woods, 2011, LKB1 is required for hepatic bile acid transport and canalicular membrane integrity in mice, Biochem. J., 434, 49, 10.1042/BJ20101721

Guigas, 2006, 5-Aminoimidazole-4-carboxamide-1β-D-ribofuranoside and metformin inhibit hepatic glucose phosphorylation by an AMP-activated protein kinase-independent effect on translocation, Diabetes, 55, 865, 10.2337/diabetes.55.04.06.db05-1178

Giri, 2008, The role of AMPK in psychosine mediated effects on oligodendrocytes and astrocytes: implication for Krabbe disease, J. Neurochem., 105, 1820, 10.1111/j.1471-4159.2008.05279.x

Labuzek, 2010, AICAR (5-aminoimidazole-4-carboxamide-1-β-4-ribofuranoside) increases the production of toxic molecules and affects the profile of cytokines release in LPS-stimulated rat primary microglial cultures, Neurotoxicology, 31, 134, 10.1016/j.neuro.2009.10.006

Zang, 2009, AMP-activated protein kinase is involved in neural stem cell growth suppression and cell cycle arrest by 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside and glucose deprivation by down-regulating phospho-retinoblastoma protein and cyclin D, J. Biol. Chem., 284, 6175, 10.1074/jbc.M806887200

Andersson, 2004, AMP-activated protein kinase plays a role in the control of food intake, J. Biol. Chem., 279, 12005, 10.1074/jbc.C300557200

Minokoshi, 2004, AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus, Nature, 428, 569, 10.1038/nature02440

Culmsee, 2001, AMP-activated protein kinase is highly expressed in neurons in the developing rat brain and promotes neuronal survival following glucose deprivation, J. Mol. Neurosci., 17, 45, 10.1385/JMN:17:1:45

Weisova, 2009, Regulation of glucose transporter 3 surface expression by the AMP-activated protein kinase mediates tolerance to glutamate excitation in neurons, J. Neurosci., 29, 2997, 10.1523/JNEUROSCI.0354-09.2009

Spasic, 2008, Drosophila alicorn is a neuronal maintenance factor protecting against activity-induced retinal degeneration, J. Neurosci., 28, 6419, 10.1523/JNEUROSCI.1646-08.2008

Kuramoto, 2007, Phospho-dependent functional modulation of GABAB receptors by the metabolic sensor AMP-dependent protein kinase, Neuron, 53, 233, 10.1016/j.neuron.2006.12.015

Terunuma, 2010, Prolonged activation of NMDA receptors promotes dephosphorylation and alters postendocytic sorting of GABAB receptors, Proc. Natl. Acad. Sci. U.S.A., 107, 13918, 10.1073/pnas.1000853107

Vingtdeux, 2010, AMP-activated protein kinase signaling activation by resveratrol modulates Amyloid-β peptide metabolism, J. Biol. Chem., 285, 9100, 10.1074/jbc.M109.060061

Li, 2007, Neuroprotective effects of adenosine monophosphate-activated protein kinase inhibition and gene deletion in stroke, Stroke, 38, 2992, 10.1161/STROKEAHA.107.490904

Concannon, 2010, AMP kinase-mediated activation of the BH3-only protein Bim couples energy depletion to stress-induced apoptosis, J. Cell Biol., 189, 83, 10.1083/jcb.200909166

Chen, 2009, Antidiabetic drug metformin (GlucophageR) increases biogenesis of Alzheimer's amyloid peptides via up-regulating BACE1 transcription, Proc. Natl. Acad. Sci. U.S.A., 106, 3907, 10.1073/pnas.0807991106

Vingtdeux, 2011, AMPK is abnormally activated in tangle- and pre-tangle-bearing neurons in Alzheimer's disease and other tauopathies, Acta Neuropathol., 121, 337, 10.1007/s00401-010-0759-x

Thornton, 2011, AMP-activated protein kinase (AMPK) is a tau kinase, activated in response to amyloid β peptide exposure, Biochem. J., 434, 503, 10.1042/BJ20101485

Chou, 2005, CGS21680 attenuates symptoms of Huntington's disease in a transgenic mouse model, J. Neurochem., 93, 310, 10.1111/j.1471-4159.2005.03029.x

Ju, 2011, Nuclear translocation of AMPK-α1 potentiates striatal neurodegeneration in Huntington's disease, J. Cell Biol., 194, 209, 10.1083/jcb.201105010

Mochel, 2012, Early alterations of brain cellular energy homeostasis in Huntington disease models, J. Biol. Chem., 287, 1361, 10.1074/jbc.M111.309849

Lim, 2012, Reduced activity of AMP-activated protein kinase protects against genetic models of motor neuron disease, J. Neurosci., 32, 1123, 10.1523/JNEUROSCI.6554-10.2012

Thornton, 2008, Muscarinic receptor activation of AMP-activated protein kinase inhibits orexigenic neuropeptide mRNA expression, J. Biol. Chem., 283, 17116, 10.1074/jbc.M708987200

Hemminki, 1998, A serine/threonine kinase gene defective in Peutz–Jeghers syndrome, Nature, 391, 184, 10.1038/34432

Sanchez-Cespedes, 2002, Inactivation of LKB1/STK11 is a common event in adenocarcinomas of the lung, Cancer Res., 62, 3659

Bright, 2009, The regulation and function of mammalian AMPK-related kinases, Acta Physiol., 196, 15, 10.1111/j.1748-1716.2009.01971.x

Lizcano, 2004, LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1, EMBO J., 23, 833, 10.1038/sj.emboj.7600110

Dazert, 2011, mTOR signaling in disease, Curr. Opin. Cell Biol., 23, 744, 10.1016/j.ceb.2011.09.003

Zoncu, 2011, mTOR: from growth signal integration to cancer, diabetes and ageing, Nat. Rev. Mol. Cell Biol., 12, 21, 10.1038/nrm3025

Manning, 2003, Rheb fills a GAP between TSC and TOR, Trends Biochem. Sci., 28, 573, 10.1016/j.tibs.2003.09.003

Kwiatkowski, 2005, Tuberous sclerosis: a GAP at the crossroads of multiple signaling pathways, Hum. Mol. Genet., 14, 251, 10.1093/hmg/ddi260

Cheng, 2004, Thr2446 is a novel mammalian target of rapamycin (mTOR) phosphorylation site regulated by nutrient status, J. Biol. Chem., 279, 15719, 10.1074/jbc.C300534200

Gwinn, 2008, AMPK phosphorylation of raptor mediates a metabolic checkpoint, Mol. Cell, 30, 214, 10.1016/j.molcel.2008.03.003

Inoki, 2003, TSC2 mediates cellular energy response to control cell growth and survival, Cell, 115, 577, 10.1016/S0092-8674(03)00929-2

Imamura, 2001, Cell cycle regulation via p53 phosphorylation by a 5′-AMP activated protein kinase activator, 5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside, in a human hepatocellular carcinoma cell line, Biochem. Biophys. Res. Commun., 287, 562, 10.1006/bbrc.2001.5627

Jones, 2005, AMP-activated protein kinase induces a p53-dependent metabolic checkpoint, Mol. Cell, 18, 283, 10.1016/j.molcel.2005.03.027

Liang, 2007, The energy sensing LKB1–AMPK pathway regulates p27kip1 phosphorylation mediating the decision to enter autophagy or apoptosis, Nat. Cell Biol., 9, 218, 10.1038/ncb1537

Dasgupta, 2009, AMP-activated protein kinase phosphorylates retinoblastoma protein to control mammalian brain development, Dev. Cell, 16, 256, 10.1016/j.devcel.2009.01.005

Bettencourt-Dias, 2004, Genome-wide survey of protein kinases required for cell cycle progression, Nature, 432, 980, 10.1038/nature03160

Alò, 1999, Fatty acid synthase (FAS) predictive strength in poorly differentiated early breast carcinomas, Tumori, 85, 35, 10.1177/030089169908500108

Milgraum, 1997, Enzymes of the fatty acid synthesis pathway are highlyexpressed in in situ breast carcinoma, Clin. Cancer Res., 3, 2115

Swinnen, 2000, Selective activation of the fatty acid synthesis pathway in human prostate cancer, Int. J. Cancer, 88, 176, 10.1002/1097-0215(20001015)88:2<176::AID-IJC5>3.0.CO;2-3

Kuhajda, 2000, Fatty-acid synthase and human cancer: new perspectives on its role in tumor biology, Nutrition, 16, 202, 10.1016/S0899-9007(99)00266-X

Kuhajda, 2000, Synthesis and antitumor activity of an inhibitor of fatty acid synthase, Proc. Natl. Acad. Sci. U.S.A., 97, 3450, 10.1073/pnas.97.7.3450

Pizer, 1998, Pharmacological inhibitors of mammalian fatty acid synthase suppress DNA replication and induce apoptosis in tumor cell lines, Cancer Res., 58, 4611

Pizer, 2000, Malonyl-coenzyme-A is a potential mediator of cytotoxicity induced by fatty-acid synthase inhibition in human breast cancer cells and xenografts, Cancer Res., 60, 213

Foretz, 1998, AMP-activated protein kinase inhibits the glucose-activated expression of fatty acid synthase gene in rat hepatocytes, J. Biol. Chem., 272, 14767, 10.1074/jbc.273.24.14767

Woods, 2000, Characterization of the role of AMP-activated protein kinase in the regulation of glucose-activated gene expression using constitutively active and dominant negative forms of the kinase, Mol. Cell. Biol., 20, 6704, 10.1128/MCB.20.18.6704-6711.2000

Zhou, 2001, Role of AMP-activated protein kinase in mechanism of metformin action, J. Clin. Invest., 108, 1167, 10.1172/JCI13505

Xiang, 2004, AMP-activated protein kinase activators can inhibit the growth of prostate cancer cells by multiple mechanisms, Biochem. Biophys. Res. Commun., 321, 161, 10.1016/j.bbrc.2004.06.133

Chajes, 2006, Acetyl-CoA carboxylase α is essential to breast cancer cell survival, Cancer Res., 66, 5287, 10.1158/0008-5472.CAN-05-1489

Hardie, 1997, The AMP-activated protein kinase: fuel gauge of the mammalian cell, Eur. J. Biochem., 246, 259, 10.1111/j.1432-1033.1997.00259.x

Foretz, 2010, Metformin inhibits hepatic gluconeogenesis in mice independently of the LKB1/AMPK pathway via a decrease in hepatic energy state, J. Clin. Invest., 120, 2355, 10.1172/JCI40671

Evans, 2005, Metformin and reduced risk of cancer in diabetic patients, Br. Med. J., 330, 1304, 10.1136/bmj.38415.708634.F7

Libby, 2009, New users of metformin are at low risk of incident cancer: a cohort study among people with type 2 diabetes, Diabetes Care, 32, 1620, 10.2337/dc08-2175

Goodwin, 2011, Obesity and insulin resistance in breast cancer: chemoprevention strategies with a focus on metformin, Breast, 20, S31, 10.1016/S0960-9776(11)70291-0

Kalender, 2010, Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner, Cell Metab., 11, 390, 10.1016/j.cmet.2010.03.014

Park, 2009, AMP-activated protein kinase promotes human prostate cancer cell growth and survival, Mol. Cancer Ther., 8, 733, 10.1158/1535-7163.MCT-08-0631

Jung, 2009, Down-regulation of AMP-activated protein kinase sensitizes DU145 carcinoma to Fas-induced apoptosis via c-FLIP degradation, Exp. Cell Res., 315, 2433, 10.1016/j.yexcr.2009.05.018

Frigo, 2011, CaM kinase kinase β-mediated activation of the growth regulatory kinase AMPK is required for androgen-dependent migration of prostate cancer cells, Cancer Res., 71, 528, 10.1158/0008-5472.CAN-10-2581

Massie, 2011, The androgen receptor fuels prostate cancer by regulating central metabolism and biosynthesis, EMBO J., 30, 2719, 10.1038/emboj.2011.158

Banko, 2011, Chemical genetic screen for AMPKα2 substrates uncovers a network of proteins involved in mitosis, Mol. Cell, 44, 878, 10.1016/j.molcel.2011.11.005

Zeng, 2000, Endothelial cell retraction is induced by PAK2 monophosphorylation of myosin II, J. Cell Sci., 113, 471, 10.1242/jcs.113.3.471

Grassie, 2011, The myosin phosphatase targeting protein (MYPT) family: a regulated mechanism for achieving substrate specificity of the catalytic subunit of protein phosphatase type 1δ, Arch. Biochem. Biophys., 510, 147, 10.1016/j.abb.2011.01.018

Ito, 2004, Myosin phosphatase: structure, regulation and function, Mol. Cell. Biochem., 259, 197, 10.1023/B:MCBI.0000021373.14288.00

Zagórska, 2010, New roles for the LKB1–NUAK pathway in controlling myosin phosphatase complexes and cell adhesion, Sci. Signaling, 3, 1, 10.1126/scisignal.2000616

Matsumura, 2005, Regulation of myosin II during cytokinesis in higher eukaryotes, Trends Cell Biol., 15, 371, 10.1016/j.tcb.2005.05.004

Lee, 2007, Energy-dependent regulation of cell structure by AMP-activated protein kinase, Nature, 447, 1017, 10.1038/nature05828

Vazquez-Martin, 2009, The active form of the metabolic sensor: AMP-activated protein kinase (AMPK) directly binds the mitotic apparatus and travels from centrosomes to the spindle midzone during mitosis and cytokinesis, Cell Cycle, 8, 2385, 10.4161/cc.8.15.9082

Horman, 2008, AMP-activated protein kinase phosphorylates and desensitizes smooth muscle myosin light chain kinase, J. Biol. Chem., 283, 18505, 10.1074/jbc.M802053200

Yun, 2011, AMP-activated protein kinase modulators: a patent review (2006–2010), Expert Opin. Ther. Pat., 21, 983, 10.1517/13543776.2011.577069

Hawley, 2010, Use of cells expressing γ subunit variants to identify diverse mechanisms of AMPK activation, Cell Metab., 11, 554, 10.1016/j.cmet.2010.04.001

Harada, 2012, Honokiol suppresses the development of post-ischemic glucose intolerance and neuronal damage in mice, J. Nat. Med., 10.1007/s11418-011-0623-x

Park, 2012, Resveratrol ameliorates aging-related metabolic phenotypes by inhibiting cAMP phosphodiesterases, Cell, 148, 421, 10.1016/j.cell.2012.01.017

de Rooij, 1998, Epac is a Rap1 guanine-nucleotide-exchange factor directly activated by cyclic AMP, Nature, 396, 474, 10.1038/24884

Kawasaki, 1998, A family of cAMP-binding proteins that directly activate Rap1, Science, 282, 2275, 10.1126/science.282.5397.2275

Oestreich, 2007, Epac-mediated activation of phospholipase Cϵ plays a critical role in β-adrenergic receptordependent enhancement of Ca2+ mobilization in cardiac myocytes, J. Biol. Chem., 282, 5488, 10.1074/jbc.M608495200

Schmidt, 2001, A new phospholipase-C–calcium signalling pathway mediated by cyclic AMP and a Rap GTPase, Nat. Cell Biol., 3, 1020, 10.1038/ncb1101-1020

Campos-Toimil, 2007, Effects of trans- and cis-resveratrol on Ca2+ handling in A7r5 vascular myocytes, Eur. J. Pharmacol., 577, 91, 10.1016/j.ejphar.2007.08.003

Sareen, 2007, Mitochondria, calcium, and calpain are key mediators of resveratrol-induced apoptosis in breast cancer, Mol. Pharmacol., 72, 1466, 10.1124/mol.107.039040

Zhou, 2011, Common variants near ATM are associated with glycemic response to metformin in type 2 diabetes, Nat. Genet., 43, 117, 10.1038/ng.735

Savitsky, 1995, A single ataxia telangiectasia gene with a product similar to PI-3 kinase, Science, 268, 1749, 10.1126/science.7792600

Woods, 2012, Activation of AMPK by metformin in hepatocytes does not require ATM, Nat. Genet., 44, 360, 10.1038/ng.2235

Yee, 2012, The role of ATM in response to metformin treatment and activation of AMPK, Nat. Genet., 44, 359, 10.1038/ng.2236

Dolinsky, 2011, Calorie restriction and resveratrol in cardiovascular health and disease, Biochim. Biophys. Acta., 1812, 1477, 10.1016/j.bbadis.2011.06.010

Hardie, 2011, Sensing of energy and nutrients by AMP-activated protein kinase, Am. J. Clin. Nutr., 93, S891, 10.3945/ajcn.110.001925

Pold, 2005, Long-term AICAR administration and exercise prevents diabetes in ZDF rats, Diabetes, 54, 928, 10.2337/diabetes.54.4.928

Guo, 2009, The AMPK agonist AICAR inhibits the growth of EGFRvIII-expressing glioblastomas by inhibiting lipogenesis, Proc. Natl. Acad. Sci. U.S.A., 106, 12932, 10.1073/pnas.0906606106

Huang, 2008, Important role of the LKB1–AMPK pathway in suppressing tumorigenesis in PTEN-deficient mice, Biochem. J., 412, 211, 10.1042/BJ20080557

Guh, 2010, Development of novel adenosine monophosphate-activated protein kinase activators, J. Med. Chem., 53, 2552, 10.1021/jm901773d

Lee, 2011, Targeting energy metabolic and oncogenic signaling pathways in triple-negative breast cancer by a novel adenosine monophosphate-activated protein kinase (AMPK) activator, J. Biol. Chem., 286, 39247, 10.1074/jbc.M111.264598

Melemedjian, 2011, Targeting adenosine monophosphate-activated protein kinase (AMPK) in preclinical models reveals a potential mechanism for the treatment of neuropathic pain, Mol. Pain, 7, 70, 10.1186/1744-8069-7-70

Kim, 2011, A small molecule AMPK activator protects the heart against ischemia-reperfusion injury, J. Mol. Cell Cardiol., 51, 24, 10.1016/j.yjmcc.2011.03.003

Viscomi, 2011, In vivo correction of COX deficiency by activation of the AMPK/PGC-1α axis, Cell Metab., 14, 80, 10.1016/j.cmet.2011.04.011