Cited by 362Metabolism, Diabetes, and CancerBiochemical and Molecular ResearchProtein Kinase Regulation and GTPase Signaling

The DOI matches its Crossref record; 34 of the 37 references it cites were found in a registry or an index.

AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge

Open access

HARDIE, D. Grahame, SALT, Ian P., HAWLEY, Simon A., DAVIES, Stephen P.·1999·Biochemical Journal

DOI 10.1042/bj3380717PMC PMC1220108

Open this paper in CoChat — free account Open PDF

Abstract

The AMP-activated protein kinase cascade is activated by elevation of AMP and depression of ATP when cellular energy charge is compromised, leading to inhibition of anabolic pathways and activation of catabolic pathways. Here we show that the system responds in intact cells in an ultrasensitive manner over a critical range of nucleotide concentrations, in that only a 6-fold increase in activating nucleotide is required in order for the maximal activity of the kinase to progress from 10% to 90%, equivalent to a co-operative system with a Hill coefficient (h) of 2.5. Modelling suggests that this sensitivity arises from two features of the system: (i) AMP acts at multiple steps in the cascade (multistep sensitivity); and (ii) the upstream kinase is initially saturated with the downstream kinase (zero-order ultrasensitivity).

Integrity signals

Registry

Crossref · 10.1042/bj3380717

Cites

34 of 34 references verified0 citation errors · 0 not checkable

Statistics

Recomputing p-values needs the paper’s full text.

Claims the paper makes

The text we found for this paper looks like another document, so its claims and self-check weren’t run. The registry and citation checks still apply.

Self-check

Percentages, sums and reported differences re-computed from the paper’s own numbers.

The text we found for this paper looks like another document, so the self-check wasn’t run.

THE AMP-ACTIVATED/SNF1 PROTEIN KINASE SUBFAMILY: Metabolic Sensors of the Eukaryotic Cell?
Hardie, D. G., Carling, D., & Carlson, M. (1998) · Annual Review of Biochemistry · doi:10.1146/annurev.biochem.67.1.821 · Cited by 1,440
The AMP‐Activated Protein Kinase: Fuel Gauge of the Mammalian Cell?
Hardie, D. G., & Carling, D. (1997) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1997.00259.x · Cited by 1,317
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
Hawley, S. A., Davison, M., Woods, A., Davies, S. P., Beri, R. K., Carling, D., & Hardie, D. G. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.44.27879 · Cited by 1,264
5-Aminoimidazole-4-Carboxamide Ribonucleoside. A Specific Method for Activating AMP-Activated Protein Kinase in Intact Cells?
Corton, J. M., Gillespie, J. G., Hawley, S. A., & Hardie, D. G. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.tb20498.x · Cited by 1,232
An amplified sensitivity arising from covalent modification in biological systems.
Goldbeter, A., & Koshland, D. E. (1981) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.78.11.6840 · Cited by 1,209
Ultrasensitivity in the mitogen-activated protein kinase cascade.
Huang, C. Y., & Ferrell, J. E. (1996) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.93.19.10078 · Cited by 1,186
The Biochemical Basis of an All-or-None Cell Fate Switch in Xenopus Oocytes
Ferrell, J. E., & Machleder, E. M. (1998) · Science · doi:10.1126/science.280.5365.895 · Cited by 1,052
AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle
Merrill, G. F., Kurth, E. J., Hardie, D. G., & Winder, W. W. (1997) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1997.273.6.e1107 · Cited by 1,048
Inactivation of acetyl-CoA carboxylase and activation of AMP-activated protein kinase in muscle during exercise
Winder, W. W., & Hardie, D. G. (1996) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.1996.270.2.e299 · Cited by 799
Evidence for 5' AMP-activated protein kinase mediation of the effect of muscle contraction on glucose transport
Hayashi, T., Hirshman, M. F., Kurth, E. J., Winder, W. W., & Goodyear, L. J. (1998) · Diabetes · doi:10.2337/diab.47.8.1369 · Cited by 774

Show all 37 references

Sorted by citations

Calmodulin-dependent protein kinase kinase-β is an alternative upstream kinase for AMP-activated protein kinase
Hawley, S. A., Pan, D. A., Mustard, K. J., Ross, L., Bain, J., Edelman, A. M., Frenguelli, B. G., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2005.05.009 · Cited by 1,589
Self-citation
Metformin: An Old Drug for the Treatment of Diabetes But a New Drug for the Protection of the Endothelium
Kinaan, M., Ding, H., & Triggle, C. R. (2015) · Medical Principles and Practice · doi:10.1159/000381643 · Cited by 1,515
AMP-Activated Protein Kinase in Metabolic Control and Insulin Signaling
Towler, M. C., & Hardie, D. G. (2007) · Circulation Research · doi:10.1161/01.res.0000256090.42690.05 · Cited by 1,262
AMPK: Sensing Glucose as well as Cellular Energy Status
Lin, S., & Hardie, D. G. (2017) · Cell Metabolism · doi:10.1016/j.cmet.2017.10.009 · Cited by 1,198
The AMP-activated protein kinase pathway – new players upstream and downstream
Hardie, D. G. (2004) · Journal of Cell Science · doi:10.1242/jcs.01540 · Cited by 1,163
The Anti-diabetic Drugs Rosiglitazone and Metformin Stimulate AMP-activated Protein Kinase through Distinct Signaling Pathways
Fryer, L. G. D., Patel, A. P., & Carling, D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m202489200 · Cited by 1,035
Minireview: The AMP-Activated Protein Kinase Cascade: The Key Sensor of Cellular Energy Status
Hardie, D. G. (2003) · Endocrinology · doi:10.1210/en.2003-0982 · Cited by 994
A Role for AMP-Activated Protein Kinase in Contraction- and Hypoxia-Regulated Glucose Transport in Skeletal Muscle
Mu, J., Brozinick, J. T., Valladares, O., Bucan, M., & Birnbaum, M. J. (2001) · Molecular Cell · doi:10.1016/s1097-2765(01)00251-9 · Cited by 924
Management of cellular energy by the AMP‐activated protein kinase system
Hardie, D. G., Scott, J. W., Pan, D. A., & Hudson, E. R. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00560-x · Cited by 868
The Antianginal Drug Trimetazidine Shifts Cardiac Energy Metabolism From Fatty Acid Oxidation to Glucose Oxidation by Inhibiting Mitochondrial Long-Chain 3-Ketoacyl Coenzyme A Thiolase
Kantor, P. F., Lucien, A., Kozak, R., & Lopaschuk, G. D. (2000) · Circulation Research · doi:10.1161/01.res.86.5.580 · Cited by 817
AMP-Activated Protein Kinase – Development of the Energy Sensor Concept
Hardie, D. G., Hawley, S. A., & Scott, J. W. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.108944 · Cited by 813
AMP‐activated protein kinase: the energy charge hypothesis revisited
Hardie, D. G., & Hawley, S. A. (2001) · BioEssays · doi:10.1002/bies.10009 · Cited by 794
Use of Cells Expressing γ Subunit Variants to Identify Diverse Mechanisms of AMPK Activation
Hawley, S. A., Ross, F. A., Chevtzoff, C., Green, K. A., Evans, A., Fogarty, S., Towler, M. C., Brown, L. J., Ogunbayo, O. A., Evans, A. M., et al. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.04.001 · Cited by 773
AMP-activated protein kinase: the current landscape for drug development
Steinberg, G. R., & Carling, D. (2019) · Nature Reviews Drug Discovery · doi:10.1038/s41573-019-0019-2 · Cited by 785
Membrane Fatty Acid Transporters as Regulators of Lipid Metabolism: Implications for Metabolic Disease
Glatz, J. F. C., Luiken, J. J. F. P., & Bonen, A. (2010) · Physiological Reviews · doi:10.1152/physrev.00003.2009 · Cited by 776
Hypoxic Pulmonary Vasoconstriction
Sylvester, J. T., Shimoda, L. A., Aaronson, P. I., & Ward, J. P. T. (2012) · Physiological Reviews · doi:10.1152/physrev.00041.2010 · Cited by 743
Resveratrol stimulates AMP kinase activity in neurons
Dasgupta, B., & Milbrandt, J. (2007) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0610068104 · Cited by 723
AMPK: a key regulator of energy balance in the single cell and the whole organism
Hardie, D. G. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.116 · Cited by 727
The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism
Hawley, S. A., Gadalla, A. E., Olsen, G. S., & Hardie, D. G. (2002) · Diabetes · doi:10.2337/diabetes.51.8.2420 · Cited by 696
Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade
Sanders, M. J., Grondin, P., Hegarty, B. D., Snowden, M. A., & Carling, D. (2007) · Biochemical Journal · doi:10.1042/bj20061520 · Cited by 677
Characterization of AMP-activated protein kinase γ-subunit isoforms and their role in AMP binding
CHEUNG, P. C. F., SALT, I. P., DAVIES, S. P., HARDIE, D. G., & CARLING, D. (2000) · Biochemical Journal · doi:10.1042/bj3460659 · Cited by 637
Self-citation
The regulation of AMP-activated protein kinase by phosphorylation
STEIN, S. C., Woods, A., Jones, N. A., DAVISON, M. D., & Carling, D. (2000) · Biochemical Journal · doi:10.1042/bj3450437 · Cited by 605
Knockout of the α2 but Not α1 5′-AMP-activated Protein Kinase Isoform Abolishes 5-Aminoimidazole-4-carboxamide-1-β-4-ribofuranosidebut Not Contraction-induced Glucose Uptake in Skeletal Muscle
Jørgensen, S. B., Viollet, B., Andreelli, F., Frøsig, C., Birk, J. B., Schjerling, P., Vaulont, S., Richter, E. A., & Wojtaszewski, J. F. P. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m306205200 · Cited by 553
AMPK: A Key Sensor of Fuel and Energy Status in Skeletal Muscle
Hardie, D. G., & Sakamoto, K. (2006) · Physiology · doi:10.1152/physiol.00044.2005 · Cited by 536
A genetically encoded fluorescent reporter of ATP:ADP ratio
Berg, J., Hung, Y. P., & Yellen, G. (2009) · Nature Methods · doi:10.1038/nmeth.1288 · Cited by 493
Effects of resveratrol on lifespan in Drosophila melanogaster and Caenorhabditis elegans
Bass, T. M., Weinkove, D., Houthoofd, K., Gems, D., & Partridge, L. (2007) · Mechanisms of Ageing and Development · doi:10.1016/j.mad.2007.07.007 · Cited by 447
AMP-Activated Protein Kinase as a Drug Target
Hardie, D. G. (2006) · The Annual Review of Pharmacology and Toxicology · doi:10.1146/annurev.pharmtox.47.120505.105304 · Cited by 411
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
Woods, A., Azzout‐Marniche, D., Foretz, M., STEIN, S. C., Lemarchand, P., Ferré, P., Foufelle, F., & Carling, D. (2000) · Molecular and Cellular Biology · doi:10.1128/mcb.20.18.6704-6711.2000 · Cited by 417
5-aminoimidazole-4-carboxamide riboside mimics the effects of insulin on the expression of the 2 key gluconeogenic genes PEPCK and glucose-6-phosphatase.
Lochhead, P. A., Salt, I. P., Walker, K. S., Hardie, D. G., & Sutherland, C. D. (2000) · Diabetes · doi:10.2337/diabetes.49.6.896 · Cited by 391
AMPK inhibition in health and disease
Viollet, B., Horman, S., Leclerc, J., Lantier, L., Foretz, M., Billaud, M., Giri, S., & Andreelli, F. (2010) · Critical Reviews in Biochemistry and Molecular Biology · doi:10.3109/10409238.2010.488215 · Cited by 383
Energy-sensing and signaling by AMP-activated protein kinase in skeletal muscle
Winder, W. W. (2001) · Journal of Applied Physiology · doi:10.1152/jappl.2001.91.3.1017 · Cited by 375
Roles of 5′-AMP-activated protein kinase (AMPK) in mammalian glucose homoeostasis
Rutter, G. A., Xavier, G. D. S., & Leclerc, I. (2003) · Biochemical Journal · doi:10.1042/bj20030048 · Cited by 335
C75, a Fatty Acid Synthase Inhibitor, Reduces Food Intake via Hypothalamic AMP-activated Protein Kinase
Kim, E. K., Miller, I., Aja, S. M., Landree, L. E., Pinn, M. L., McFadden, J. M., Kuhajda, F. P., Moran, T. H., & Ronnett, G. V. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m402165200 · Cited by 313
The Regulation of AMP-Activated Protein Kinase by H2O2
Choi, S.-L., Kim, S.-J., Lee, K.-T., Kim, J., Mu, J., Birnbaum, M. J., Soo Kim, S., & Ha, J. (2001) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2001.5544 · Cited by 294
AMPK as a mediator of hormonal signalling
Lim, C. T., Kola, B., & Korbonits, M. (2009) · Journal of Molecular Endocrinology · doi:10.1677/jme-09-0063 · Cited by 304
Predominant α2/β2/γ3 AMPK activation during exercise in human skeletal muscle
Birk, J. B., & Wojtaszewski, J. F. P. (2006) · The Journal of Physiology · doi:10.1113/jphysiol.2006.120972 · Cited by 293
The regulation of AMP-activated protein kinase by upstream kinases
Carling, D., Sanders, M. J., & Woods, A. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.124 · Cited by 295
Seasonal Regulation of Reproduction in Mammals
Hazlerigg, D. G., & Simonneaux, V. (2014) · Elsevier eBooks · doi:10.1016/b978-0-12-397175-3.00034-x · Cited by 288
A Critical Review of the Evidence That Metformin Is a Putative Anti-Aging Drug That Enhances Healthspan and Extends Lifespan
Mohammed, I., Hollenberg, M. D., Ding, H., & Triggle, C. R. (2021) · Frontiers in Endocrinology · doi:10.3389/fendo.2021.718942 · Cited by 278
Cardiac Insulin-Resistance and Decreased Mitochondrial Energy Production Precede the Development of Systolic Heart Failure After Pressure-Overload Hypertrophy
Zhang, L., Jaswal, J. S., Ussher, J. R., Sankaralingam, S., Wagg, C. S., Zaugg, M., & Lopaschuk, G. D. (2013) · Circulation Heart Failure · doi:10.1161/circheartfailure.112.000228 · Cited by 273
Chemical Genetic Screen for AMPKα2 Substrates Uncovers a Network of Proteins Involved in Mitosis
Banko, M. R., Allen, J. J., Schaffer, B. E., Wilker, E., Tsou, P., White, J. L., Villén, J., Wang, B., Kim, S. R., Sakamoto, K., et al. (2011) · Molecular Cell · doi:10.1016/j.molcel.2011.11.005 · Cited by 252
Mechanisms for Increased Glycolysis in the Hypertrophied Rat Heart
Nascimben, L., Ingwall, J. S., Lorell, B. H., Pinz, I. M., Schultz, V., Tornheim, K., & Tian, R. (2004) · Hypertension · doi:10.1161/01.hyp.0000144292.69599.0c · Cited by 242
Substrate Competition as a Source of Ultrasensitivity in the Inactivation of Wee1
Kim, S. Y., & Ferrell, J. E. (2007) · Cell · doi:10.1016/j.cell.2007.01.039 · Cited by 220
Ghrelin: a hormone regulating food intake and energy homeostasis
Gil‐Campos, M., Aguilera, C. M., Cañete, R., & Gil, Á. (2006) · British Journal Of Nutrition · doi:10.1079/bjn20061787 · Cited by 218
The role of interleukin‐6 in insulin resistance, body fat distribution and energy balance
Hoene, M., & Weigert, C. (2007) · Obesity Reviews · doi:10.1111/j.1467-789x.2007.00410.x · Cited by 226
Ultrasensitivity part I: Michaelian responses and zero-order ultrasensitivity
Ferrell, J. E., & Ha, S. H. (2014) · Trends in Biochemical Sciences · doi:10.1016/j.tibs.2014.08.003 · Cited by 213
Thrombin Activates AMP-Activated Protein Kinase in Endothelial Cells via a Pathway Involving Ca2+/Calmodulin-Dependent Protein Kinase Kinase β
Stahmann, N., Woods, A., Carling, D., & Heller, R. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00383-06 · Cited by 214
Pyruvate kinase: current status of regulatory and functional properties
Muñoz-Márquez, M. E., & Ponce‐Rivas, E. (2003) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/s1096-4959(03)00081-2 · Cited by 209
Role of AMP-activated protein kinase in the regulation by glucose of islet beta cell gene expression
Xavier, G. D. S., Leclerc, I., Salt, I. P., Doiron, B., Hardie, D. G., Kahn, A., & Rutter, G. A. (2000) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.97.8.4023 · Cited by 203
Fungicidal Drugs Induce a Common Oxidative-Damage Cellular Death Pathway
Belenky, P., Camacho, D., & Collins, J. J. (2013) · Cell Reports · doi:10.1016/j.celrep.2012.12.021 · Cited by 199
Characterization of the role of the AMP-activated protein kinase in the stimulation of glucose transport in skeletal muscle cells
Fryer, L. G. D., Foufelle, F., Barnes, K., Baldwin, S. A., Woods, A., & Carling, D. (2002) · Biochemical Journal · doi:10.1042/0264-6021:3630167 · Cited by 198
Regulation of spinach SNF1‐related (SnRK1) kinases by protein kinases and phosphatases is associated with phosphorylation of the T loop and is regulated by 5′‐AMP
Sugden, C., Crawford, R. M., Halford, N. G., & Hardie, D. G. (1999) · The Plant Journal · doi:10.1046/j.1365-313x.1999.00532.x · Cited by 195
Roles of AMP-activated Protein Kinase in Alzheimer’s Disease
Cai, Z., Yan, L., Li, K., Quazi, S. H., & Zhao, B. (2012) · NeuroMolecular Medicine · doi:10.1007/s12017-012-8173-2 · Cited by 198
AMP-activated protein kinase: An energy sensor and survival mechanism in the reinstatement of metabolic homeostasis
Sharma, A., Anand, S. K., Singh, N., Dwivedi, U. N., & Kakkar, P. (2023) · Experimental Cell Research · doi:10.1016/j.yexcr.2023.113614 · Cited by 207
Keeping the home fires burning: AMP-activated protein kinase
Hardie, D. G. (2018) · Journal of The Royal Society Interface · doi:10.1098/rsif.2017.0774 · Cited by 195
Ultrasensitive response motifs: basic amplifiers in molecular signalling networks
Zhang, Q., Bhattacharya, S., & Andersen, M. E. (2013) · Open Biology · doi:10.1098/rsob.130031 · Cited by 186
Stimulation of Glucose Transport by AMP-activated Protein Kinase via Activation of p38 Mitogen-activated Protein Kinase
Xi, X., Han, J., & Zhang, J. (2001) · Journal of Biological Chemistry · doi:10.1074/jbc.m102824200 · Cited by 180
Role of AMPKα2 in basal, training-, and AICAR-induced GLUT4, hexokinase II, and mitochondrial protein expression in mouse muscle
Jørgensen, S. B., Treebak, J. T., Viollet, B., Schjerling, P., Vaulont, S., Wojtaszewski, J. F. P., & Richter, E. A. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00243.2006 · Cited by 181
Physiological role of AMP-activated protein kinase in the heart: graded activation during exercise
Coven, D. L., Hu, X., Cong, L., Bergeron, R., Shulman, G. I., Hardie, D. G., & Young, L. H. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00171.2003 · Cited by 175
Dissociation of AMP-activated protein kinase activation and glucose transport in contracting slow-twitch muscle.
Derave, W., Ai, H., Ihlemann, J., Witters, L. A., Kristiansen, S., Richter, E. A., & Ploug, T. (2000) · Diabetes · doi:10.2337/diabetes.49.8.1281 · Cited by 168
AMP-activated protein kinase: a key system mediating metabolic responses to exercise
HARDIE, D. G. (2004) · Medicine & Science in Sports & Exercise · doi:10.1249/01.mss.0000106171.38299.64 · Cited by 165
Self-citation
Intrasteric control of AMPK via the γ1 subunit AMP allosteric regulatory site
Adams, J. J., Chen, Z., van Denderen, B. J. W., Morton, C. J., Parker, M. W., Witters, L. A., Stapleton, D., & Kemp, B. E. (2003) · Protein Science · doi:10.1110/ps.03340004 · Cited by 169
The CBS Domain: A Protein Module with an Emerging Prominent Role in Regulation
Baykov, A. A., Tuominen, H. K., & Lahti, R. (2011) · ACS Chemical Biology · doi:10.1021/cb200231c · Cited by 165
Physiological functions of peroxisome proliferator-activated receptor β
Neels, J. G., & Grimaldi, P. A. (2014) · Physiological Reviews · doi:10.1152/physrev.00027.2013 · Cited by 161
Multiple Regulatory Layers of SREBP1/2 by SIRT6
Elhanati, S., Kanfi, Y., Varvak, A., Roichman, A., Carmel-Gross, I., Barth, S., Gibor, G., & Cohen, H. Y. (2013) · Cell Reports · doi:10.1016/j.celrep.2013.08.006 · Cited by 161
Small Molecule Antagonizes Autoinhibition and Activates AMP-activated Protein Kinase in Cells
Pang, T., Zhang, Z., Gu, M., Qiu, B., Yu, L.-F., Cao, P.-R., Shao, W., Su, M., Li, J.-Y., Nan, F., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m710114200 · Cited by 159
Fatal Congenital Heart Glycogenosis Caused by a Recurrent Activating R531Q Mutation in the γ2-Subunit of AMP-Activated Protein Kinase (PRKAG2), Not by Phosphorylase Kinase Deficiency
Burwinkel, B., Scott, J. W., Bührer, C., van Landeghem, F. K. H., Cox, G. F., Wilson, C. J., Hardie, D. G., & Kilimann, M. W. (2005) · The American Journal of Human Genetics · doi:10.1086/430840 · Cited by 155
AMPK: a cellular energy sensor primarily regulated by AMP
Gowans, G. J., & Hardie, D. G. (2014) · Biochemical Society Transactions · doi:10.1042/bst20130244 · Cited by 152
AMP-activated Protein Kinase Mediates Carotid Body Excitation by Hypoxia
Wyatt, C. N., Mustard, K. J., Pearson, S. A., Dallas, M. L., Atkinson, L., Kumar, P., Peers, C., Hardie, D. G., & Evans, A. M. (2006) · Journal of Biological Chemistry · doi:10.1074/jbc.m608742200 · Cited by 148
5′-AMP-activated protein kinase activity and subunit expression in exercise-trained human skeletal muscle
Nielsen, J. N., Mustard, K. J., Graham, D. A., Yu, H., MacDonald, C., Pilegaard, H., Goodyear, L. J., Hardie, D. G., Richter, E. A., & Wojtaszewski, J. F. P. (2003) · Journal of Applied Physiology · doi:10.1152/japplphysiol.00642.2002 · Cited by 149
Potential Role for AMP-Activated Protein Kinase in Hypoglycemia Sensing in the Ventromedial Hypothalamus
McCrimmon, R. J., Fan, X., Ding, Y., Zhu, W., Jacob, R. J., & Sherwin, R. S. (2004) · Diabetes · doi:10.2337/diabetes.53.8.1953 · Cited by 153
Nutrient sensing and metabolic decisions
Lindsley, J. E., & Rutter, J. P. (2004) · Comparative Biochemistry and Physiology Part B Biochemistry and Molecular Biology · doi:10.1016/j.cbpc.2004.06.014 · Cited by 146
Respiratory chain dysfunction in skeletal muscle does not cause insulin resistance
Wredenberg, A., Freyer, C., Sandström, M. E., Katz, A., Wibom, R., Westerblad, H., & Larsson, N.-G. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.09.029 · Cited by 141
In Vivo Activation of AMP-Activated Protein Kinase Attenuates Diabetes-Enhanced Degradation of GTP Cyclohydrolase I
Wang, S., Xu, J. C., Song, P., Viollet, B., & Zou, M. (2009) · Diabetes · doi:10.2337/db09-0267 · Cited by 137
Retracted
Effects of endurance training on activity and expression of AMP-activated protein kinase isoforms in rat muscles
Durante, P. E., Mustard, K. J., Park, S.-H., Winder, W. W., & Hardie, D. G. (2002) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00404.2001 · Cited by 137
Expression of the AMP‐activated protein kinase β1 and β2 subunits in skeletal muscle
Chen, Z., Heierhorst, J., Mann, R. J., Mitchelhill, K. I., Michell, B. J., Witters, L. A., Lynch, G. S., Kemp, B. E., & Stapleton, D. (1999) · FEBS Letters · doi:10.1016/s0014-5793(99)01371-x · Cited by 134
Constitutive UCP3 overexpression at physiological levels increases mouse skeletal muscle capacity for fatty acid transport and oxidation
Bézaire, V., Spriet, L. L., Campbell, S., Sabet, N., Gerrits, M. F., Bonen, A., & Harper, M. (2005) · The FASEB Journal · doi:10.1096/fj.04-2765fje · Cited by 133
5-aminoimidazole-4-carboxamide ribonucleoside (AICAR) inhibits insulin-stimulated glucose transport in 3T3-L1 adipocytes.
Salt, I. P., Connell, J. M. C., & Gould, G. W. (2000) · Diabetes · doi:10.2337/diabetes.49.10.1649 · Cited by 132
AMP-activated Protein Kinase Inhibits Transforming Growth Factor-β-induced Smad3-dependent Transcription and Myofibroblast Transdifferentiation
Mishra, R., Cool, B. L., Laderoute, K. R., Foretz, M., Viollet, B., & Simonson, M. S. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m800902200 · Cited by 129
Adenosine Monophosphate-Activated Protein Kinase (AMPK) as a New Target for Antidiabetic Drugs: A Review on Metabolic, Pharmacological and Chemical Considerations
Gruzman, A., Babai-Shani, G., & Sasson, S. (2009) · The Review of Diabetic Studies · doi:10.1900/rds.2009.6.13 · Cited by 128
AMP-activated protein kinase agonists increase mRNA content of the muscle-specific ubiquitin ligases MAFbx and MuRF1 in C2C12 cells
Krawiec, B. J., Nystrom, G. J., Frost, R. A., Jefferson, L. S., & Lang, C. H. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00622.2006 · Cited by 125
Functional Analysis of Mutations in the γ2 Subunit of AMP-activated Protein Kinase Associated with Cardiac Hypertrophy and Wolff-Parkinson-White Syndrome
Daniel, T. D., & Carling, D. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m207093200 · Cited by 121
Ischaemic Preconditioning Protects Against Ischaemia/Reperfusion Injury: Emerging Concepts
Pasupathy, S., & Homer‐Vanniasinkam, S. (2004) · European Journal of Vascular and Endovascular Surgery · doi:10.1016/j.ejvs.2004.11.005 · Cited by 118
Protection of Epithelial Barrier Function by the Crohn's Disease Associated Gene Protein Tyrosine Phosphatase N2
Scharl, M. M., Paul, G., Weber, A., Jung, B., Docherty, M. J., Hausmann, M., Rogler, G., Barrett, K. E., & McCole, D. F. (2009) · Gastroenterology · doi:10.1053/j.gastro.2009.07.078 · Cited by 120
AMP-Activated Protein Kinase: A Master Switch in Glucose and Lipid Metabolism
Hardie, D. G. (2004) · Reviews in Endocrine and Metabolic Disorders · doi:10.1023/b:remd.0000021433.63915.bb · Cited by 117
Activation of AMP-Activated Protein Kinase Within the Ventromedial Hypothalamus Amplifies Counterregulatory Hormone Responses in Rats With Defective Counterregulation
McCrimmon, R. J., Fan, X., Cheng, H. M., McNay, E. C., Chan, O. T. M., Shaw, M., Ding, Y., Zhu, W., & Sherwin, R. S. (2006) · Diabetes · doi:10.2337/db05-1359 · Cited by 116
Tau and mTOR: The Hotspots for Multifarious Diseases in Alzheimer's Development
Mueed, Z., Tandon, P., Maurya, S. K., Deval, R., Kamal, M. A., & Poddar, N. K. (2019) · Frontiers in Neuroscience · doi:10.3389/fnins.2018.01017 · Cited by 111
AMP-activated Protein Kinase Mediates the Interferon-γ-induced Decrease in Intestinal Epithelial Barrier Function
Scharl, M. M., Paul, G., Barrett, K. E., & McCole, D. F. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.046292 · Cited by 110
Neither LKB1 Nor AMPK Are the Direct Targets of Metformin
Hardie, D. G. (2006) · Gastroenterology · doi:10.1053/j.gastro.2006.07.032 · Cited by 113
Global Phosphoproteome of HT-29 Human Colon Adenocarcinoma Cells
Kim, J., Tannenbaum, S. R., & White, F. M. (2005) · Journal of Proteome Research · doi:10.1021/pr050048h · Cited by 110
A homologue of AMP-activated protein kinase in Drosophila melanogaster is sensitive to AMP and is activated by ATP depletion
Pan, D. A., & Hardie, D. G. (2002) · Biochemical Journal · doi:10.1042/bj20020703 · Cited by 112
Dual Mechanisms Regulating AMPK Kinase Action in the Ischemic Heart
Baron, S. J., Li, J., Russell, R. R., Neumann, D., Miller, E. J., Tuerk, R. D., Wallimann, T., Hurley, R. L., Witters, L. A., & Young, L. H. (2005) · Circulation Research · doi:10.1161/01.res.0000155723.53868.d2 · Cited by 108
Ppm1E is an in cellulo AMP-activated protein kinase phosphatase
Voß, M., Paterson, J., Kelsall, I. R., Martín‐Granados, C., Hastie, C. J., Peggie, M. W., & Cohen, P. T. W. (2010) · Cellular Signalling · doi:10.1016/j.cellsig.2010.08.010 · Cited by 111
A Potential Role for AMP-Activated Protein Kinase in Meiotic Induction in Mouse Oocytes
Downs, S. M., Hudson, E. R., & Hardie, D. G. (2002) · Developmental Biology · doi:10.1006/dbio.2002.0613 · Cited by 107
Hepatic energy state is regulated by glucagon receptor signaling in mice
Berglund, E. D., Lee, R. S., Lustig, D. G., Lynes, S. E., Donahue, E. P., Camacho, R. C., Meredith, M. E., Magnuson, M. A., Charron, M. J., & Wasserman, D. H. (2009) · Journal of Clinical Investigation · doi:10.1172/jci38650 · Cited by 108
Genome-Based Metabolic Mapping and 13C Flux Analysis Reveal Systematic Properties of an Oleaginous Microalga Chlorella protothecoides
Wu, C., Xiong, W., Dai, J., & Wu, Q. (2015) · Plant Physiology · doi:10.1104/pp.114.250688 · Cited by 108
The Relationship between AMP-activated Protein Kinase Activity and AMP Concentration in the Isolated Perfused Rat Heart
Frederich, M., & Balschi, J. A. (2002) · Journal of Biological Chemistry · doi:10.1074/jbc.m107128200 · Cited by 105
AMP-activated protein kinase and human cancer: cancer metabolism revisited
Kuhajda, F. P. (2008) · International Journal of Obesity · doi:10.1038/ijo.2008.121 · Cited by 105
AMPK activation with glabridin ameliorates adiposity and lipid dysregulation in obesity
Lee, J.-W., Choe, S. S., Jang, H., Kim, J., Jeong, H. W., Jo, H., Jeong, K.-H., Tadi, S., Park, M. G., Kwak, T. H., et al. (2012) · Journal of Lipid Research · doi:10.1194/jlr.m022897 · Cited by 102
AMP-activated protein kinase (AMPK) in the rock crab, Cancer irroratus : an early indicator of temperature stress
Frederich, M., O'Rourke, M., Furey, N. B., & Jost, J. A. (2009) · Journal of Experimental Biology · doi:10.1242/jeb.021998 · Cited by 105

Authors: HARDIE, D. G., SALT, I. P., HAWLEY, S. A., & DAVIES, S. P.
Affiliations: University of Dundee (GB)
ORCID: HARDIE, D. Grahame
SALT, Ian P.
Venue: Biochemical Journal
Publisher: Portland Press Ltd.
Published: 1999-03-08
Volume: 338
Issue: 3
Pages: 717-722
ISSN: 0264-6021 (ISSN-L)
1470-8728
DOI: 10.1042/bj3380717
PMC: PMC1220108
OpenAlex: W2014670133
Cited by: 362
References: 37
Citations by year: 2026: 5 · 2025: 5 · 2024: 5 · 2023: 4 · 2022: 5 · 2021: 7 · 2020: 5 · 2019: 5 · 2018: 13 · 2017: 7 · 2016: 12 · 2015: 15 · 2014: 16 · 2013: 17 · 2012: 20
FWCI: 5.05
Type: journal article
Language: en
Open access: bronze
doi.org
Locations: Biochemical Journal (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
York University
University of Bristol
University at Buffalo
Medical Research Council
Topics: Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
Keywords: AMPK, ultrasensitivity, AMP, ATP, Hill coefficient, cooperative activation, energy homeostasis
MeSH terms: Amino Acid Sequence, Cell Line, Energy Metabolism, Kinetics, Models, Biological, Molecular Sequence Data, Multienzyme Complexes, Sensitivity and Specificity, Protein Serine-Threonine Kinases, AMP-Activated Protein Kinases

About these checks

Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.

Statistics and arithmetic are recomputed, not judged.

Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.

What counts as a claim ›How we measure confidence ›How we check this ›

Are you an author, or do you see a problem with this page? Request a review

AMP-activated protein kinase: an ultrasensitive system for monitoring cellular energy charge

Abstract

Overview

Integrity signals

Verification

Claims the paper makes

Self-check

Citations

Cites

Cited by

Related

Metadata

Record

About these checks