Cited by 606Metabolism, Diabetes, and CancerBiochemical and Molecular ResearchProtein Kinase Regulation and GTPase Signaling

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5′‐AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP‐activated protein kinase. Studies using bacterially expressed human protein phosphatase‐2C α and native bovine protein phosphatase‐2A c

S P Davies, Nicholas R. Helps, Philip Cohen, David Grahame Hardie·1995·FEBS Letters

DOI 10.1016/0014-5793(95)01368-7

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Abstract

Human protein phosphatase-2C alpha (PP2C alpha) was purified to homogeneity after expression in Escherichia coli. AMP inhibited the dephosphorylation of AMP-activated protein kinase (AMPK), but not phosphocasein, by PP2C alpha. The concentration dependence and the effects of other nucleotides (ATP and formycin A-5'-monophosphate) suggest that AMP acts by binding to the same site which causes direct allosteric activation of AMPK. A similar, although less pronounced, effect was observed with another protein phosphatase (PP2AC). We have now shown that AMPK activates the AMPK cascade by four mechanisms, which should make the system exquisitely sensitive to changes in AMP concentration.

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Serine/threonine protein phosphatases
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[3] Expression and nitrogen-15 labeling of proteins for proton and nitrogen-15 nuclear magnetic resonance
Muchmore, D. C., McIntosh, L. P., Russell, C., Anderson, D. E., & Dahlquist, F. W. (1989) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(89)77005-1 · Cited by 454
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Carling, D., Clarke, P. R., Zammit, V. A., & Hardie, D. G. (1989) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1989.tb15186.x · Cited by 418
[37] Protein phosphatase-1 and protein phosphatase-2A from rabbit skeletal muscle
Cohen, P., Alemany, S., Therese, B. A., Resink, J., Strålfors, P., & Tung, H. Y. L. (1988) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(88)59039-0 · Cited by 411
Yeast SNF1 is functionally related to mammalian AMP-activated protein kinase and regulates acetyl-CoA carboxylase in vivo.
Woods, A., Munday, M. R., Scott, J., Yang, X., Carlson, M., & Carling, D. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)32198-1 · Cited by 409
Mammalian AMP-activated protein kinase shares structural and functional homology with the catalytic domain of yeast Snf1 protein kinase.
Mitchelhill, K. I., Stapleton, D., Gao, G., House, C. M., Michell, B. J., Katsis, F., Witters, L. A., & Kemp, B. E. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(17)41951-x · Cited by 338

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10.1111/j.1432-1033.1995.0558k.x · DOI
Clarke P.R., 1991, Adv. Protein Phosphatases, 6, 187
MacKintosh C. (1993) in: (Hardie D.G. eds.) pp. 214–216. Oxford University Press Oxford.

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BackgroundInfluential
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Background
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Anti-inflammatory Property of AMP-activated Protein Kinase
Noor, H. B., Mou, N. A., Salem, L., Shimul, M. F. A., Biswas, S., Akther, R., Khan, S., Raihan, S., Mohib, M. M., & Sagor, M. A. T. (2019) · Anti-Inflammatory & Anti-Allergy Agents in Medicinal Chemistry · doi:10.2174/1871523018666190830100022 · Cited by 34
Plant-Derived Flavonoids as AMPK Activators: Unveiling Their Potential in Type 2 Diabetes Management through Mechanistic Insights, Docking Studies, and Pharmacokinetics
Moon, D. O. (2024) · Applied Sciences · doi:10.3390/app14198607 · Cited by 40
Appetite and Metabolic Effects of Ghrelin and Cannabinoids: Involvement of AMP-Activated Protein Kinase
van Thuijl, H., Kola, B., & Korbonits, M. (2007) · Vitamins and hormones · doi:10.1016/s0083-6729(06)77006-6 · Cited by 31
Protein phosphatase type 2Cα and 2Cβ are involved in fatty acid-induced apoptosis of neuronal and endothelial cells
Schwarz, S., Hufnagel, B., Dworak, M., Klumpp, S., & Krieglstein, J. (2006) · APOPTOSIS · doi:10.1007/s10495-006-6982-1 · Cited by 31
“Oleic acid is known to activate various enzymes such as cAMP-activated protein kinase (AMPK) [31], phospholipases C [32] and D [33] or phosphoinositol-3-kinase (PI3K) [21] and to be involved in other mechanisms leading to apoptosis apart from PP2C.”
Background
BAY-3827 and SBI-0206965: Potent AMPK Inhibitors That Paradoxically Increase Thr172 Phosphorylation
Hawley, S. A., Russell, F. M., Ross, F. A., & Hardie, D. G. (2023) · International Journal of Molecular Sciences · doi:10.3390/ijms25010453 · Cited by 32
“Cells were lysed rapidly in situ on culture plates using ice-cold lysis medium containing phosphatase inhibitors, as described previously [55].”
Method
Intracellular signaling of the AMP-activated protein kinase
Dërmaku‐Sopjani, M., & Sopjani, M. (2019) · Advances in protein chemistry and structural biology · doi:10.1016/bs.apcsb.2018.12.001 · Cited by 31
Skeletal muscle AMPK is not activated during 2 h of moderate intensity exercise at ∼65% in endurance trained men
McConell, G. K., Wadley, G. D., Plastrier, K. L., & Linden, K. C. (2020) · The Journal of Physiology · doi:10.1113/jp277619 · Cited by 34
“PP2C has previously been shown to inhibit the activity of both AMPK α1 and α2 isoforms (Davies et al. 1995); however, further studies are required to determine whether changes in PP2C activity occur following exercise training.”
Background
AMPK and the Challenge of Treating Hypoxic Pulmonary Hypertension
Flores, K., Siqués, P., Brito, J., & Arribas, S. M. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms23116205 · Cited by 30
AMP-activated protein kinase kinase activity and phosphorylation of AMP-activated protein kinase in contracting muscle of sedentary and endurance-trained rats
Hurst, D., Taylor, E. B., Cline, T. D., Greenwood, L. J., Compton, C. L., Lamb, J. D., & Winder, W. W. (2005) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00155.2005 · Cited by 29
“For example, AMP is a major activator of the cascade and has been shown to activate AMPK via 3 distinct mechanisms: direct allosteric activation of kinase activity, allosterically making it a better substrate for AMPKK phosphorylation, and inhibiting dephosphorylation of Thr172 by protein phosphatases (5, 15, 16, 20).”
Background
Novel Small-Molecule AMP-Activated Protein Kinase Allosteric Activator with Beneficial Effects in db/db Mice
Zhang, L., Xu, L., Zhou, H., Wu, L., Li, Y., Pang, T., Xia, C.-M., Qiu, B., Gu, M., Dong, T., et al. (2013) · PLoS ONE · doi:10.1371/journal.pone.0072092 · Cited by 30
“To date, there are two different assay methods, the traditional filter assay [31] and microarrayed compound screening (mARCS) [15,32].”
BackgroundMethod
Hypoxia and AMP independently regulate AMP-activated protein kinase activity in heart
Frederich, M., Zhang, L., & Balschi, J. A. (2005) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00558.2004 · Cited by 29
Points of integration between the intracellular energy sensor AMP-activated protein kinase (AMPK) activity and the somatotroph axis function
Tulipano, G., Faggi, L., Sibilia, V., & Giustina, A. (2012) · Endocrine · doi:10.1007/s12020-012-9732-x · Cited by 28
ERK1/2 activated PHLPP1 induces skeletal muscle ER stress through the inhibition of a novel substrate AMPK
Behera, S., Kapadia, B. B., Kain, V., Alamuru-Yellapragada, N. P., Murunikkara, V., Kumar, S. T., Babu, P. P., Seshadri, S., Shivarudraiah, P., Hiriyan, J., et al. (2018) · Biochimica et Biophysica Acta (BBA) - Molecular Basis of Disease · doi:10.1016/j.bbadis.2018.02.019 · Cited by 27
LKB1 biology: assessing the therapeutic relevancy of LKB1 inhibitors
Trelford, C. B., & Shepherd, T. G. (2024) · Cell Communication and Signaling · doi:10.1186/s12964-024-01689-5 · Cited by 28
“AMP binding allosterically activates AMPK and protects AMPK from dephosphorylation [54, 55].”
Background
NQO1-induced activation of AMPK contributes to cancer cell death by oxygen-glucose deprivation
Lee, H., Oh, E., Choi, B., Park, M., Lee, J.-K., Lee, J., & Park, H. J. (2015) · Scientific Reports · doi:10.1038/srep07769 · Cited by 28
AMP-activated protein kinase can be allosterically activated by ADP but AMP remains the key activating ligand
Hawley, S. A., Russell, F. M., & Hardie, D. G. (2024) · Biochemical Journal · doi:10.1042/bcj20240082 · Cited by 27
“Human GST-tagged α 2 kinase domain (1 – 310) [24], LKB1: STRAD-α :MO25-α complexes [25], GST-tagged CaMKK2 [26], and PPM1A (PP2C α ) [27] were produced as described.”
AMPK in Intestinal Health and Disease: A Multifaceted Therapeutic Target for Metabolic and Inflammatory Disorders
Yibcharoenporn, C., Muanprasat, C., Moonwiriyakit, A., Satitsri, S., & Pathomthongtaweechai, N. (2025) · Drug Design Development and Therapy · doi:10.2147/dddt.s507489 · Cited by 27
How cells sense energy
Hardie, D. G. (2011) · Nature · doi:10.1038/472176a · Cited by 30
Short-Chain Fatty Acid Production and Functional Aspects on Host Metabolism
Tungland, B. C. (2018) · Elsevier eBooks · doi:10.1016/b978-0-12-814649-1.00002-8 · Cited by 29
A new role for AMP ‐activated protein kinase in the circadian regulation of L‐type voltage‐gated calcium channels in late‐stage embryonic retinal photoreceptors
Huang, C. C., Shi, L., Lin, C., Kim, A. J., Ko, M. L., & Ko, G. Y. ‐. (2015) · Journal of Neurochemistry · doi:10.1111/jnc.13349 · Cited by 27
“(2015) 135, 727--741 727 targeting its Thr172, such as live kinase B1, Ca2+/calmodulin-dependent protein kinase kinase b (Hawley et al. 2003; Woods et al. 2005; Mihaylova and Shaw 2011), and protein phosphatase 2A and 2C (Davies et al. 1995; Kudo et al. 1996; Wu et al. 2007).”
Background
Homo-oligomerization and Activation of AMP-activated Protein Kinase Are Mediated by the Kinase Domain αG-Helix
Scholz, R., Suter, M., Weimann, T., Polge, C., Konarev, P. V., Thali, R. F., Tuerk, R. D., Viollet, B., Wallimann, T., Schlattner, U., et al. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.047670 · Cited by 27
Uniquely Conserved Non-translated Regions are Involved in Generation of the Two Major Transcripts of Protein Phosphatase 2Cβ
Seroussi, E., Shani, N., Ben‐Meir, D., Chajut, A., Divinski, I., Faier, S., Gery, S., Karby, S., Kariv-Inbal, Z., Sella-Tavor, O., et al. (2001) · Journal of Molecular Biology · doi:10.1006/jmbi.2001.4967 · Cited by 26
Reduced purine biosynthesis in humans after their divergence from Neandertals
Stepanova, V. V., Moczulska, K. E., Vacano, G. N., Kurochkin, I., Ju, X.-C., Riesenberg, S., Macak, D., Maričić, T., Dombrowski, L., Schörnig, M., et al. (2021) · eLife · doi:10.7554/elife.58741 · Cited by 27
“Of particular relevance may be phosphorylation of the threonine at position 172 in the α-subunit [pAMPKα(Thr172)], which is enhanced when AMP is bound by the γ-subunit (Davies et al., 1995) (Hawley et al., 1995).”
Background
Atorvastatin and pitavastatin enhance lipoprotein lipase production in L6 skeletal muscle cells through activation of adenosine monophosphate-activated protein kinase
Ohira, M., Endo, K., Saiki, A., Miyashita, Y., Terai, K., Murano, T., Watanabe, F., Tatsuno, I., & Shirai, K. (2012) · Metabolism · doi:10.1016/j.metabol.2012.03.010 · Cited by 25
“[24] Davies SP, Helps NR, Cohen PT, et al.”
Background
Past strategies and future directions for identifying AMP-activated protein kinase (AMPK) modulators
Sinnett, S. E., & Brenman, J. E. (2014) · Pharmacology & Therapeutics · doi:10.1016/j.pharmthera.2014.02.008 · Cited by 26
Role of AMP-Activated Protein Kinase for Regulating Post-exercise Insulin Sensitivity
Kjøbsted, R., Wojtaszewski, J. F. P., & Treebak, J. T. (2016) · Proceedings of the Fourth International Symposium on Polarization Phenomena in Nuclear Reactions · doi:10.1007/978-3-319-43589-3_5 · Cited by 26
Protein phosphatase 5 promotes hepatocarcinogenesis through interaction with AMP-activated protein kinase
Chen, Y., Hung, M., Chu, P., Chao, T., Tsai, M.-H., Chen, L., Hsiao, Y., Shih, C.-T., Hsieh, F., & Chen, K. (2017) · Biochemical Pharmacology · doi:10.1016/j.bcp.2017.05.010 · Cited by 25
AMPK Attenuates Bupivacaine-induced Neurotoxicity
Lee, S. J., Shin, T. J., Kang, I., Ha, J., Lee, S., & Kim, H. J. (2010) · Journal of Dental Research · doi:10.1177/0022034510366823 · Cited by 24
“Phosphorylated AMPK (pAMPK) is considered the barometer of AMPK activity (Davies et al., 1995).”
Background
Aerobic Exercise’s Reversal of Insulin Resistance by Activating AMPKα–ACC–CPT1 Signaling in the Skeletal Muscle of C57BL/6 Mice
Niu, Y., Yuan, H., & Fu, L. (2010) · International Journal of Sport Nutrition and Exercise Metabolism · doi:10.1123/ijsnem.20.5.370 · Cited by 24
Isoform-selective 5′-AMP-activated protein kinase-dependent preconditioning mechanisms to prevent postischemic leukocyte-endothelial cell adhesive interactions
Gaskin, F. S., Kamada, K., Zuidema, M. Y., JONES, A. W., Rubin, L. J., & Korthuis, R. J. (2011) · American Journal of Physiology-Heart and Circulatory Physiology · doi:10.1152/ajpheart.00944.2010 · Cited by 24
“The binding of AMP or ZMP also increase AMPK activity by increasing the duration of the active state, which is accomplished by decreasing the affinity of phosphorylated AMPK for deactivating phosphatases such as protein phosphatase 2C (13).”
Background
IMPAD1 functions as mitochondrial electron transport inhibitor that prevents ROS production and promotes lung cancer metastasis through the AMPK-Notch1-HEY1 pathway
Yang, Y., Wang, Y., Hsiao, M., Lo, S. J., Chang, Y., Jan, Y., Lai, T., Lee, Y.-C., Hsieh, Y.-C., & Yuan, S. F. (2020) · Cancer Letters · doi:10.1016/j.canlet.2020.04.025 · Cited by 24
The role of AMPK in regulation of Na+,K+-ATPase in skeletal muscle: does the gauge always plug the sink?
Pirkmajer, S., Petrič, M., & Chibalin, A. (2021) · Journal of Muscle Research and Cell Motility · doi:10.1007/s10974-020-09594-3 · Cited by 24
Herbal therapy as a promising approach for regulation on lipid profiles: A review of molecular aspects
Roghani‐Shahraki, H., Karimian, M., Valipour, S., Behjati, M., Arefnezhad, R., & Mousavi, A. (2021) · Journal of Cellular Physiology · doi:10.1002/jcp.30282 · Cited by 24
“Dephosphorylation of LKB1‐dependent AMPKα phosphorylation at Thr172 residue is inhibited after AMP binding to the AMPKγ‐subunit, which subsequently improves AMPKα phosphorylation (Davies et al., 1995; Hawley et al., 1995).”
Background
Immunohistochemical localization of the neural cannabinoid receptor in rat brain
Pettit, D. A. D., Harrison, M. P., Olson, J. M., Spencer, R. F., & Cabral, G. A. (1998) · Journal of Neuroscience Research · doi:10.1002/(sici)1097-4547(19980201)51:3 · Cited by 228
Tumor Necrosis Factor-related Apoptosis-inducing Ligand (TRAIL)-Troglitazone-induced Apoptosis in Prostate Cancer Cells Involve AMP-activated Protein Kinase
Santha, S., Viswakarma, N., Das, S., Rana, A., & Rana, B. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m115.663526 · Cited by 23
Augmentation of Reduced Folate Carrier-Mediated Folate/Antifolate Transport through an Antiport Mechanism with 5-Aminoimidazole-4-Carboxamide Riboside Monophosphate
Visentin, M., Zhao, R., & Goldman, I. D. (2012) · Molecular Pharmacology · doi:10.1124/mol.112.078642 · Cited by 23
“Through the formation of ZMP, AICAR leads to the activation of AMP kinase (Davies et al., 1995; Corradetti and Guan, 2006).”
Background
Reciprocal Association between the Apical Junctional Complex and AMPK: A Promising Therapeutic Target for Epithelial/Endothelial Barrier Function?
Tsukita, K., Yano, T., Tamura, A., & Tsukita, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20236012 · Cited by 25
“Activation of AMPK is determined by the balance of the following three factors (Figure 2) [48,49,57]: (1) the AMP/ATP ratio [48,57], (2) the activity of upstream kinases to phosphorylate α-subunit Thr-172 including liver kinase B1 (LKB1) and Ca2+/calmodulin-dependent protein kinase kinase β (CaMKKβ) [58,59], and (3) t…”
Background
Molecular mechanisms of appetite and obesity: a role for brain AMPK
de Morentin, P. B. M., Urisarri, A., Couce, M. L., & López, M. (2016) · Clinical Science · doi:10.1042/cs20160048 · Cited by 21
Blocking AMPK β1 myristoylation enhances AMPK activity and protects mice from high-fat diet-induced obesity and hepatic steatosis
Neopane, K., Kozlov, N., Negoita, F., Murray‐Segal, L., Brink, R. A., Hoque, A., Ovens, A. J., Tjin, G., McAloon, L. M., Yu, D., et al. (2022) · Cell Reports · doi:10.1016/j.celrep.2022.111862 · Cited by 22
Transient activation of fission yeast AMPK is required for cell proliferation during osmotic stress
Schutt, K. L., & Moseley, J. B. (2017) · Molecular Biology of the Cell · doi:10.1091/mbc.e17-04-0235 · Cited by 23
“…canonical mechanism in which AMP-bound γ subunit generates a conformation that inhibits the rate of dephosphorylation of the α subunit by inactivating phosphatases (Davies et al., 1995; Jiang and Carlson, 1996; Suter et al., 2006, Sanders et al., 2007, Rubenstein et al., 2008, Mayer et al., 2011).”
BackgroundInfluential

Authors: Davies, S. P., Helps, N. R., Cohen, P., & Hardie, D. G.
Affiliations: University of Dundee (GB)
ORCID: Philip Cohen
David Grahame Hardie
Venue: FEBS Letters
Publisher: Wiley
Published: 1995-12-27
Volume: 377
Issue: 3
Pages: 421-425
ISSN: 0014-5793 (ISSN-L)
1873-3468
DOI: 10.1016/0014-5793(95)01368-7
OpenAlex: W2030636484
Cited by: 595
References: 19
Citations by year: 2026: 7 · 2025: 6 · 2024: 18 · 2023: 11 · 2022: 16 · 2021: 25 · 2020: 23 · 2019: 17 · 2018: 21 · 2017: 28 · 2016: 25 · 2015: 30 · 2014: 36 · 2013: 32 · 2012: 35
FWCI: 3.22
Type: journal article
Language: en
Open access: closed
Licence: onlinelibrary.wiley.com/termsAndConditions#vor (vor, 1532 d)
Locations: FEBS Letters (publishedVersion)
PubMed (publishedVersion)
Funders: Wellcome Trust
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, AMP, dephosphorylation, phosphorylation, allosteric activation, nucleotide binding, formycin A, energy homeostasis
MeSH terms: Protein Phosphatase 2C, Adenosine Monophosphate, Allosteric Regulation, Animals, Base Sequence, Cattle, Dose-Response Relationship, Drug, Enzyme Activation, Escherichia coli, Humans, Isoenzymes, Models, Biological, Molecular Sequence Data, Multienzyme Complexes, Nucleotides, Phosphoprotein Phosphatases, Phosphorylation, Protein Kinases, Recombinant Proteins, Signal Transduction, Protein Serine-Threonine Kinases, Saccharomyces cerevisiae Proteins, Protein Phosphatase 2, AMP-Activated Protein Kinases

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5′‐AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP‐activated protein kinase. Studies using bacterially expressed human protein phosphatase‐2C α and native bovine protein phosphatase‐2A c

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