AMP-activated protein kinase phosphorylates and inactivates liver glycogen synthase
Abstract
Recombinant muscle GYS1 (glycogen synthase 1) and recombinant liver GYS2 were phosphorylated by recombinant AMPK (AMP-activated protein kinase) in a time-dependent manner and to a similar stoichiometry. The phosphorylation site in GYS2 was identified as Ser7, which lies in a favourable consensus for phosphorylation by AMPK. Phosphorylation of GYS1 or GYS2 by AMPK led to enzyme inactivation by decreasing the affinity for both UDP-Glc (UDP-glucose) [assayed in the absence of Glc-6-P (glucose-6-phosphate)] and Glc-6-P (assayed at low UDP-Glc concentrations). Incubation of freshly isolated rat hepatocytes with the pharmacological AMPK activators AICA riboside (5-aminoimidazole-4-carboxamide-1-β-D-ribofuranoside) or A769662 led to persistent GYS inactivation and Ser7 phosphorylation, whereas inactivation by glucagon treatment was transient. In hepatocytes from mice harbouring a liver-specific deletion of the AMPK catalytic α1/α2 subunits, GYS2 inactivation by AICA riboside and A769662 was blunted, whereas inactivation by glucagon was unaffected. The results suggest that GYS inactivation by AMPK activators in hepatocytes is due to GYS2 Ser7 phosphorylation.
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In liver, GS inactivation by AMPK activators (AICAR and A769662) occurs at S7 phosphorylation site on GS2, which is the liver-specific isoform.
“In liver, GS inactivation by AMPK activators (AICAR and A769662) occurs at S7 phosphorylation site on GS2, which is the liver-specific isoform [136].”
From AMPK and Exercise: Glucose Uptake and Insulin Sensitivity (2013) · cites this paper as [136]
Cites
Bradford, M. M. (1976) · Analytical Biochemistry · doi:10.1016/0003-2697(76)90527-3 · Cited by 255,302 · see citing works
Role of AMP-Activated Protein Kinase in Mechanism of Metformin Action
Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., et al. (2001) · Journal of Clinical Investigation · doi:10.1172/jci13505 · Cited by 5,652 · see citing works
Kahn, B. B., Alquier, T., Carling, D., & Hardie, D. G. (2005) · Cell Metabolism · doi:10.1016/j.cmet.2004.12.003 · Cited by 2,799 · see citing works
The Kinase LKB1 Mediates Glucose Homeostasis in Liver and Therapeutic Effects of Metformin
Shaw, R. J., Lamia, K. A., Vasquez, D., Koo, S.-H., Bardeesy, N., DePinho, R. A., Montminy, M., & Cantley, L. C. (2005) · Science · doi:10.1126/science.1120781 · Cited by 1,950 · see citing works
AMP-activated protein kinase: an energy sensor that regulates all aspects of cell function
Hardie, D. G. (2011) · Genes & Development · doi:10.1101/gad.17420111 · Cited by 1,638 · see citing works
Steinberg, G. R., & Kemp, B. E. (2009) · Physiological Reviews · doi:10.1152/physrev.00011.2008 · Cited by 1,633 · see citing works
Thomas, J. A., Schlender, K. K., & Larner, J. (1968) · Analytical Biochemistry · doi:10.1016/0003-2697(68)90127-9 · Cited by 1,198 · see citing works
Foretz, M., Hébrard, S., Leclerc, J., Zarrinpashneh, E., Soty, M., Mithieux, G., Sakamoto, K., Andreelli, F., & Viollet, B. (2010) · Journal of Clinical Investigation · doi:10.1172/jci40671 · Cited by 1,181 · see citing works
Self-citationUse 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 · see citing works
Holmes, B. F., Kurth-Kraczek, E. J., & Winder, W. W. (1999) · Journal of Applied Physiology · doi:10.1152/jappl.1999.87.5.1990 · Cited by 489 · see citing works
Viollet, B., Guigas, B., Leclerc, J., Hébrard, S., Lantier, L., Mounier, R., Andréelli, F., & Foretz, M. (2009) · Acta Physiologica · doi:10.1111/j.1748-1716.2009.01970.x · Cited by 486 · see citing works
Self-citationRoach, P. (2002) · Current Molecular Medicine · doi:10.2174/1566524024605761 · Cited by 468 · see citing works
Deprez, J., Vertommen, D., Alessi, D. R., Hue, L., & Rider, M. H. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.28.17269 · Cited by 447 · see citing works
Self-citationMechanism of Action of A-769662, a Valuable Tool for Activation of AMP-activated Protein Kinase
Göransson, O., McBride, A., Hawley, S. A., Ross, F. A., Shpiro, N., Foretz, M., Viollet, B., Hardie, D. G., & Sakamoto, K. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706536200 · Cited by 433 · see citing works
Self-citationThe Glycogen-Binding Domain on the AMPK β Subunit Allows the Kinase to Act as a Glycogen Sensor
McBride, A., Ghilagaber, S., Nikolaev, A., & Hardie, D. G. (2009) · Cell Metabolism · doi:10.1016/j.cmet.2008.11.008 · Cited by 432 · see citing works
Hue, L., Bontemps, F., & Hers, H. G. (1975) · Biochemical Journal · doi:10.1042/bj1520105 · Cited by 356 · see citing works
Self-citationSanders, M. J., Ali, Z. S., Hegarty, B. D., Heath, R., Snowden, M. A., & Carling, D. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.m706543200 · Cited by 347 · see citing works
Hudson, E. R., Pan, D. A., James, J., Lucocq, J. M., Hawley, S. A., Green, K. A., Baba, O., Terashima, T., & Hardie, D. G. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00249-5 · Cited by 332 · see citing works
Dale, S. J., Wilson, W. A., Edelman, A. M., & Hardie, D. G. (1995) · FEBS Letters · doi:10.1016/0014-5793(95)00172-6 · Cited by 324 · see citing works
New Insights Into the Role and Mechanism of Glycogen Synthase Activation by Insulin
Lawrence, J. C., & Roach, P. J. (1997) · Diabetes · doi:10.2337/diab.46.4.541 · Cited by 311 · see citing works
Carling, D., & Grahame Hardie, D. (1989) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(89)90014-1 · Cited by 296 · see citing works
Control of glycogen synthase by hierarchal protein phosphorylation
Roach, P. J. (1990) · The FASEB Journal · doi:10.1096/fasebj.4.12.2168324 · Cited by 270 · see citing works
Wojtaszewski, J. F. P., Jørgensen, S. B., Hellsten, Y., Hardie, D. G., & Richter, E. A. (2002) · Diabetes · doi:10.2337/diabetes.51.2.284 · Cited by 261 · see citing works
Scott, J. W., van Denderen, B. J. W., Jørgensen, S. B., Honeyman, J. E., Steinberg, G. R., Oakhill, J. S., Iseli, T. J., Koay, A. Z., Gooley, P. R., Stapleton, D., et al. (2008) · Chemistry & Biology · doi:10.1016/j.chembiol.2008.10.005 · Cited by 252 · see citing works
Jørgensen, S. B., Nielsen, J. N., Birk, J. B., Olsen, G. S., Viollet, B., Andreelli, F., Schjerling, P., Vaulont, S., Hardie, D. G., Hansen, B. F., et al. (2004) · Diabetes · doi:10.2337/diabetes.53.12.3074 · Cited by 241 · see citing works
Self-citationControl of glycogen deposition
Ferrer, J. C., Favre, C., Gomis, R. R., Fernández-Novell, J. M., Garcı́a-Rocha, M., de la Iglesia, N., Cid, E., & Guinovart, J. J. (2003) · FEBS Letters · doi:10.1016/s0014-5793(03)00565-9 · Cited by 234 · see citing works
Self-citation[6] Catalytic subunit of cAMP-dependent protein kinase
Reimann, E. M., & Beham, R. A. (1983) · Methods in enzymology on CD-ROM/Methods in enzymology · doi:10.1016/0076-6879(83)99039-0 · Cited by 211 · see citing works
Stalmans, W., De Wulf, H., Hue, L., & Hers, H. (1974) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1974.tb03252.x · Cited by 210 · see citing works
Self-citationAllosteric Regulation of Glycogen Synthase Controls Glycogen Synthesis in Muscle
Bouskila, M., Hunter, R. W., Ibrahim, A. F. M., Delattre, L., Peggie, M., van Diepen, J. A., Voshol, P. J., Jensen, J., & Sakamoto, K. (2010) · Cell Metabolism · doi:10.1016/j.cmet.2010.10.006 · Cited by 196 · see citing works
Self-citationBontemps, F., Hue, L., & Hers, H. G. (1978) · Biochemical Journal · doi:10.1042/bj1740603 · Cited by 192 · see citing works
Self-citationGuigas, B., Bertrand, L., Taleux, N., Foretz, M., Wiernsperger, N. F., Vertommen, D., Andréelli, F., Viollet, B., & Hue, L. (2006) · Diabetes · doi:10.2337/diabetes.55.04.06.db05-1178 · Cited by 181 · see citing works
Self-citationCohen, P. (1999) · Philosophical Transactions of the Royal Society of London. Series B: Biological Sciences · doi:10.1098/rstb.1999.0399 · Cited by 158 · see citing works
Hunter, R. W., Treebak, J. T., Wojtaszewski, J. F. P., & Sakamoto, K. (2011) · Diabetes · doi:10.2337/db10-1148 · Cited by 151 · see citing works
Self-citationFlotow, H., & Roach, P. J. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)60501-0 · Cited by 136 · see citing works
Regulation of hepatic metabolism by AMPK
Foretz, M., & Viollet, B. (2010) · Journal of Hepatology · doi:10.1016/j.jhep.2010.09.014 · Cited by 120 · see citing works
Self-citationGuigas, B., Taleux, N., Foretz, M., Détaille, D., Andréelli, F., Viollet, B., & Hue, L. (2007) · Biochemical Journal · doi:10.1042/bj20070105 · Cited by 117 · see citing works
Self-citationAMP-activated Protein Kinase Phosphorylates and Desensitizes Smooth Muscle Myosin Light Chain Kinase
Horman, S., Morel, N., Vertommen, D., Hussain, N., Neumann, D., Beauloye, C., Najjar, N. E., Forcet, C., Viollet, B., Walsh, M. P., et al. (2008) · Journal of Biological Chemistry · doi:10.1074/jbc.m802053200 · Cited by 116 · see citing works
Self-citationEffect of AICAR Treatment on Glycogen Metabolism in Skeletal Muscle
Aschenbach, W. G., Hirshman, M. F., FUJII, N. L., Sakamoto, K., Howlett, K. F., & Goodyear, L. J. (2002) · Diabetes · doi:10.2337/diabetes.51.3.567 · Cited by 114 · see citing works
Self-citationKrause, U., Rider, M. H., & Hue, L. (1996) · Journal of Biological Chemistry · doi:10.1074/jbc.271.28.16668 · Cited by 113 · see citing works
Self-citationPhosphorylation of Ser640 in Muscle Glycogen Synthase by DYRK Family Protein Kinases
Skurat, A. V., & Dietrich, A. D. (2004) · Journal of Biological Chemistry · doi:10.1074/jbc.m301769200 · Cited by 110 · see citing works
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 106 · see citing works
Skurat, A. V., Wang, Y., & Roach, P. J. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)47282-1 · Cited by 102 · see citing works
Dual Regulation of Muscle Glycogen Synthase during Exercise by Activation and Compartmentalization
Prats, C., Helge, J. W., Nordby, P., Qvortrup, K., Ploug, T., Dela, F., & Wojtaszewski, J. F. P. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m900845200 · Cited by 78 · see citing works
Barré, L. K., Richardson, C., Hirshman, M. F., Brozinick, J. T., Fiering, S., Kemp, B. E., Goodyear, L. J., & Witters, L. A. (2006) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00369.2006 · Cited by 72 · see citing works
Bai, G., Zhang, Z. J., Werner, R., Nuttall, F. Q., Tan, A. W., & Lee, E. Y. (1990) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)39007-6 · Cited by 67 · see citing works
Vernia, S., Solaz-Fuster, M. C., Gimeno-Alcañiz, J. V., Rubio, T., García-Haro, L., Foretz, M., de Córdoba, S., & Sanz, P. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808492200 · Cited by 59 · see citing works
Self-citationControl of Liver Glycogen Synthase Activity and Intracellular Distribution by Phosphorylation
R�os, S., Garcı́a-Rocha, M., Domínguez, J. E., Ferrer, J. C., & Guinovart, J. J. (2009) · Journal of Biological Chemistry · doi:10.1074/jbc.m808576200 · Cited by 58 · see citing works
Self-citationControl of mammalian glycogen synthase by PAS kinase
Wilson, W. A., Skurat, A. V., Probst, B., DePaoli-Roach, A. A., Roach, P. J., & Rutter, J. P. (2005) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0508481102 · Cited by 50 · see citing works
Peeters, A., Fraisl, P., van den Berg, S. A. A., van Themaat, E. V. L., van Kampen, A. H. C., Rider, M. H., Takemori, H., van Dijk, K. W., Veldhoven, P. P. V., Carmeliet, P., et al. (2011) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.299727 · Cited by 49 · see citing works
Self-citationShared control of hepatic glycogen synthesis by glycogen synthase and glucokinase
Gomis, R. R., Ferrer, J. C., & Guinovart, J. J. (2000) · Biochemical Journal · doi:10.1042/bj3510811 · Cited by 48 · see citing works
Self-citationLai, Y., Stuenæs, J. T., Kuo, C., & Jensen, J. (2007) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00113.2007 · Cited by 48 · see citing works
Miranda, L., Horman, S., Potter, I. D., Hue, L., Jensen, J., & Rider, M. H. (2007) · Pflügers Archiv - European Journal of Physiology · doi:10.1007/s00424-007-0368-2 · Cited by 40 · see citing works
Self-citationSkurat, A. V., & Roach, P. J. (1996) · Biochemical Journal · doi:10.1042/bj3130045 · Cited by 31 · see citing works
Stalmans, W., De Wulf, H., Hue, L., & Hers, H. G. (1974) · Digital Access to Libraries · Cited by 1 · see citing works
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Yuan, J., Dong, X., Yap, J., & Hu, J. (2020) · Journal of Hematology & Oncology · doi:10.1186/s13045-020-00949-4 · Cited by 500 · see citing works
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Hardie, D. G., Ross, F. A., & Hawley, S. A. (2012) · Chemistry & Biology · doi:10.1016/j.chembiol.2012.08.019 · Cited by 373 · see citing works
Srivastava, R. A. K., Pinkosky, S. L., Filippov, S. I., Hanselman, J. C., Cramer, C. T., & Newton, R. S. (2012) · Journal of Lipid Research · doi:10.1194/jlr.r025882 · Cited by 297 · see citing works
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AMP-activated protein kinase: maintaining energy homeostasis at the cellular and whole-body levels
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AMPK signaling and its targeting in cancer progression and treatment
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Keeping the home fires burning: AMP-activated protein kinase
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Salt, I. P., & Hardie, D. G. (2017) · Circulation Research · doi:10.1161/circresaha.117.309633 · Cited by 186 · see citing works
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Regulation of AMP-activated protein kinase by natural and synthetic activators
Hardie, D. G. (2015) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2015.06.002 · Cited by 176 · see citing works
Adapt and conquer: Metabolic flexibility in cancer growth, invasion and evasion
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AMPK in the brain: its roles in glucose and neural metabolism
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Johanns, M., Lai, Y., Hsu, M. F., Jacobs, R., Vertommen, D., Sande, J. V., Dumont, J. E., Woods, A., Carling, D., Hue, L., et al. (2016) · Nature Communications · doi:10.1038/ncomms10856 · Cited by 143 · see citing works
Self-citationThe strange case of AMPK and cancer: Dr Jekyll or Mr Hyde?
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Hinson, J. T., Chopra, A., Lowe, A., Sheng, C. C., Gupta, R. M., Rajarajan, K., O’Sullivan, J., Rowe, G. C., Wakimoto, H., Gorham, J., et al. (2016) · Cell Reports · doi:10.1016/j.celrep.2016.11.066 · Cited by 100 · see citing works
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Promise and challenges for direct small molecule AMPK activators
Olivier, S., Foretz, M., & Viollet, B. (2018) · Biochemical Pharmacology · doi:10.1016/j.bcp.2018.01.049 · Cited by 87 · see citing works
Self-citationXiao, J., Bei, Y., Liu, J., Dimitrova‐Shumkovska, J., Kuang, D., Zhou, Q., Li, J., Yang, Y., Xiang, Y., Wang, F., et al. (2015) · Journal of Cellular and Molecular Medicine · doi:10.1111/jcmm.12733 · Cited by 75 · see citing works
Houddane, A., Bultot, L., Novellasdemunt, L., Johanns, M., Gueuning, M.-A., Vertommen, D., Coulie, P. G., Bartrons, R., Hue, L., & Rider, M. H. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.02.019 · Cited by 75 · see citing works
Self-citationJohanns, M., Ruys, S. P. D., Houddane, A., Vertommen, D., Herinckx, G., Hue, L., Proud, C. G., & Rider, M. H. (2017) · Cellular Signalling · doi:10.1016/j.cellsig.2017.05.010 · Cited by 75 · see citing works
Self-citationChromatin recruitment of activated AMPK drives fasting response genes co-controlled by GR and PPARα
Ratman, D., Mylka, V., Bougarne, N., Pawlak, M., Caron, S., Hennuyer, N., Paumelle, R., Cauwer, L. D., Thommis, J., Rider, M. H., et al. (2016) · Nucleic Acids Research · doi:10.1093/nar/gkw742 · Cited by 70 · see citing works
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Rana, S., Blowers, E. C., & Natarajan, A. (2014) · Journal of Medicinal Chemistry · doi:10.1021/jm401994c · Cited by 62 · see citing works
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Bonanno, L., Zulato, E., Pavan, A., Attili, I., Pasello, G., Conte, P., & Indraccolo, S. (2019) · International Journal of Molecular Sciences · doi:10.3390/ijms20081874 · Cited by 52 · see citing works
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Brewer, M. K., & Gentry, M. S. (2019) · Advances in neurobiology · doi:10.1007/978-3-030-27480-1_2 · Cited by 46 · see citing works
Giansanti, P., Stokes, M. P., Silva, J. C., Scholten, A., & Heck, A. J. R. (2013) · Molecular & Cellular Proteomics · doi:10.1074/mcp.o113.028456 · Cited by 46 · see citing works
Exercise training improves liver steatosis in mice
Alex, S., Boss, A., Heerschap, A., & Kersten, S. (2015) · Nutrition & Metabolism · doi:10.1186/s12986-015-0026-1 · Cited by 43 · see citing works
Functional characterization of AMP-activated protein kinase signaling in tumorigenesis
Cheng, J., Zhang, T., Ji, H., Tao, K., Guo, J., & Wei, W. (2016) · Biochimica et Biophysica Acta (BBA) - Reviews on Cancer · doi:10.1016/j.bbcan.2016.09.006 · Cited by 44 · see citing works
AMP-Activated Protein Kinase: Friend or Foe in Cancer?
Vara‐Ciruelos, D., Dandapani, M., & Hardie, D. G. (2019) · Annual Review of Cancer Biology · doi:10.1146/annurev-cancerbio-030419-033619 · Cited by 39 · see citing works
PHD3 Loss Promotes Exercise Capacity and Fat Oxidation in Skeletal Muscle
Yoon, H., Spinelli, J. B., Zaganjor, E., Wong, S. J., German, N. J., Randall, E. C., Dean, A., Clermont, A. C., Paulo, J. A., Garcia, D., et al. (2020) · Cell Metabolism · doi:10.1016/j.cmet.2020.06.017 · Cited by 37 · see citing works
AMPK inhibits liver gluconeogenesis: fact or fiction?
Johanns, M., Hue, L., & Rider, M. H. (2023) · Biochemical Journal · doi:10.1042/bcj20220582 · Cited by 42 · see citing works
Self-citationChronic hypoxia leads to a glycolytic phenotype and suppressed HIF-2 signaling in PC12 cells
Zhdanov, A. V., Dmitriev, R. I., Golubeva, A. V., Gavrilova, S. A., & Papkovsky, D. B. (2013) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/j.bbagen.2013.02.016 · Cited by 36 · see citing works
Wang, D., Tian, Y., Wang, Q., Zhang, Y., Ye, B., Zuo, Z., He, J., Pan, Z., Sun, D., Zou, J., et al. (2024) · Aquaculture · doi:10.1016/j.aquaculture.2024.740574 · Cited by 34 · see citing works
Cheng, H., Qin, Y., Dhillon, R. S., Dowell, J., Denu, J. M., & Pamenter, M. E. (2022) · Metabolites · doi:10.3390/metabo12010056 · Cited by 33 · see citing works
AMPK in myocardial infarction and diabetes: the yin/yang effect
Moussa, A., & Li, J. (2012) · Acta Pharmaceutica Sinica B · doi:10.1016/j.apsb.2012.06.001 · Cited by 32 · see citing works
Unravelling the role of fatty acid metabolism in cancer through the FOXO3-FOXM1 axis
Saavedra-García, P., Nichols, K., Mahmud, Z., Fan, L. Y.-N., & Lam, E. W. ‐. (2017) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2017.01.012 · Cited by 32 · see citing works
Kakhlon, O., Glickstein, H., Feinstein, N., Liu, Y., Baba, O., Terashima, T., Akman, H. O., DiMauro, S., & Lossos, A. (2013) · Journal of Neurochemistry · doi:10.1111/jnc.12277 · Cited by 31 · see citing works
AMP-Activated Protein Kinase Signalling in Cancer and Cardiac Hypertrophy
Konhilas, Y. L. J. P. (2015) · Cardiovascular Pharmacology Open Access · doi:10.4172/2329-6607.1000154 · Cited by 29 · see citing works
Chemical genetic screen identifies Gapex-5/GAPVD1 and STBD1 as novel AMPK substrates
Ducommun, S., Deák, M., Zeigerer, A., Göransson, O., Seitz, S., Collodet, C., Madsen, A. B., Jensen, T. E., Viollet, B., Foretz, M., et al. (2019) · Cellular Signalling · doi:10.1016/j.cellsig.2019.02.001 · Cited by 28 · see citing works
Self-citationRole of the AMPK signalling pathway in the aetiopathogenesis of ocular diseases
Shukal, D. K., Malaviya, P. B., & Sharma, T. (2022) · Human & Experimental Toxicology · doi:10.1177/09603271211063165 · Cited by 27 · see citing works
From Kinases to Diseases: Investigating the Role of AMPK in Human Pathologies
Rey, V., & Tamargo‐Gómez, I. (2023) · Kinases and Phosphatases · doi:10.3390/kinasesphosphatases1030012 · Cited by 27 · see citing works
Early Treatment with Metformin Improves Neurological Outcomes in Lafora Disease
Burgos, D. F., Machío-Castello, M., Iglesias‐Cabeza, N., Giráldez, B. G., González‐Fernández, J., Sánchez‐Martín, G., Sánchez, M. P., & Serratosa, J. M. (2022) · Neurotherapeutics · doi:10.1007/s13311-022-01304-w · Cited by 26 · see citing works
Hasenour, C. M., Ridley, D. E., James, F. D., Hughey, C. C., Donahue, E. P., Viollet, B., Foretz, M., Young, J. D., & Wasserman, D. H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0170382 · Cited by 26 · see citing works
Self-citationLin, L., Zeng, L., Liu, A., Yuan, D., Peng, Y., Zhang, S., Li, Y., Chen, J., Xiao, W., & Gong, Z. (2021) · Nutrients · doi:10.3390/nu13114120 · Cited by 26 · see citing works
Bodur, Ç., Karakaş, B., Timuçin, A. C., Tezil, T., & Başağa, H. (2015) · Molecular Carcinogenesis · doi:10.1002/mc.22411 · Cited by 24 · see citing works
Jin, M., Luo, J., Zhu, T., Fang, F., Xie, S., Lu, J., Betancor, M. B., Tocher, D. R., & Zhou, Q. (2024) · Aquaculture · doi:10.1016/j.aquaculture.2024.741329 · Cited by 23 · see citing works
Insights into Transcriptional Regulation of Hepatic Glucose Production
Anyamaneeratch, K., Rojvirat, P., Sukjoi, W., & Jitrapakdee, S. (2015) · International review of cytology · doi:10.1016/bs.ircmb.2015.05.004 · Cited by 23 · see citing works
Hasani, S., Young, L. E. A., Nort, W. V., Banerjee, M., Rivas, D. R., Kim, J., Xiong, X., Sun, R. C., Gentry, M. S., Sesaki, H., et al. (2023) · Cell Death and Disease · doi:10.1038/s41419-023-06202-3 · Cited by 19 · see citing works
Hardie, D. G. (2010) · Elsevier eBooks · doi:10.1016/b978-0-12-374145-5.00073-5 · Cited by 19 · see citing works
Hasenour, C. M., Wall, M. L., Ridley, D. E., James, F. D., Hughey, C. C., Donahue, E. P., Viollet, B., Foretz, M., Young, J. D., & Wasserman, D. H. (2017) · PLoS ONE · doi:10.1371/journal.pone.0183601 · Cited by 19 · see citing works
Self-citationMultifaceted role of AMPK in autophagy: more than a simple trigger?
Mandić, M., Misirkic-Marjanovic, M., Janjetović, K., Bošnjak, M., Harhaji-Trajkovic, L. M., Trajković, V., & Vucicevic, L. M. (2025) · American Journal of Physiology-Cell Physiology · doi:10.1152/ajpcell.01058.2024 · Cited by 20 · see citing works
Jeroundi, N., Roy, C., Basset, L., Pignon, P., Preisser, L., Blanchard, S., Bocca, C., Abadie, C., Lalande-Martin, J., Guéguen, N., et al. (2024) · EMBO Reports · doi:10.1038/s44319-024-00278-4 · Cited by 18 · see citing works
Conserved versatile master regulators in signalling pathways in response to stress in plants
Balderas‐Hernández, V. E., Alvarado-Rodríguez, M., & Fraire-Velázquez, S. (2013) · AoB Plants · doi:10.1093/aobpla/plt033 · Cited by 18 · see citing works
Adiponectin regulates glycogen metabolism at the human fetal–maternal interface
Duval, F., Santos, E. D., Maury, B., Serazin-Leroy, V., Fathallah, K., Vialard, F., & Dieudonné, M. (2018) · Journal of Molecular Endocrinology · doi:10.1530/jme-18-0013 · Cited by 18 · see citing works
Adaptive responses of neuronal cells to chronic endoplasmic reticulum (ER) stress
Pham, T. N. M., Perumal, N., Manicam, C., Başoğlu, M., Eimer, S., Fuhrmann, D. C., Pietrzik, C. U., Clement, A. M., Körschgen, H., Schepers, J., et al. (2023) · Redox Biology · doi:10.1016/j.redox.2023.102943 · Cited by 16 · see citing works
dos Santos, G. A., Pereira, V. D., Roman, E. A. F. R., Ignácio-Souza, L. M., Vitorino, D. C., de Moura, R. F., Razolli, D. S., Torsoni, A. S., Velloso, L. A., & Torsoni, M. A. (2013) · PLoS ONE · doi:10.1371/journal.pone.0062669 · Cited by 17 · see citing works
RetractedProtein restriction reprograms the multi-organ proteomic landscape of mouse aging
Lu, T., Xie, Y., Wang, Y., Lin, X., Cai, X., Zhang, Y., Nie, Z., Su, C., Gou, W., Zhang, H., et al. (2025) · Cell · doi:10.1016/j.cell.2025.10.004 · Cited by 15 · see citing works
Mukherjee, U., & Maitra, S. (2023) · Aquaculture and Fisheries · doi:10.1016/j.aaf.2023.05.004 · Cited by 15 · see citing works
Kondo, K., Mori, M., Tomita, M., & Arakawa, K. (2019) · Genes to Cells · doi:10.1111/gtc.12726 · Cited by 14 · see citing works
Trefts, E., Hughey, C. C., Lantier, L., Lark, D. S., Boyd, K. L., Pozzi, A., Zent, R., & Wasserman, D. H. (2019) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00496.2018 · Cited by 14 · see citing works
Müller, M., Schubert, T., Welke, C., Maske, T., Patschkowski, T., Donhauser, E., Heinen‐Weiler, J., Hormann, F.-L., Heiles, S., Schulz, T. J., et al. (2025) · Nature Communications · doi:10.1038/s41467-025-59192-5 · Cited by 13 · see citing works
AMPK is involved in the differential neonatal performance of chicks hatching at different time
Wang, Y., Buyse, J. G., Song, Z., Decuypere, E. M. P., & Everaert, N. (2016) · General and Comparative Endocrinology · doi:10.1016/j.ygcen.2016.02.008 · Cited by 13 · see citing works
Gregersen, S., Bystrup, S., Overgaard, A., Jeppesen, P. B., Thorup, A. C. S., Jensen, E., & Hermansen, K. (2013) · The Review of Diabetic Studies · doi:10.1900/rds.2013.10.252 · Cited by 13 · see citing works
New Insight into Metformin Mechanism of Action and Clinical Application
Yan, Y., Kover, K. L., & Moore, W. V. (2020) · IntechOpen eBooks · doi:10.5772/intechopen.91148 · Cited by 12 · see citing works
Saks, V. A., Schlattner, U., Tokarska-Schlattner, M., Wallimann, T., Bagur, R., Zorman, S., Pelosse, M., Santos, P. D. D., Boucher, F. R., Käämbre, T., et al. (2013) · Springer series in biophysics · doi:10.1007/978-3-642-38505-6_11 · Cited by 12 · see citing works
Hunter, R. W., Zeqiraj, E., Morrice, N. A., Sicheri, F., & Sakamoto, K. (2014) · Protein Expression and Purification · doi:10.1016/j.pep.2014.12.007 · Cited by 12 · see citing works
Self-citationRegulation of glycogen synthase in muscle and its role in Type 2 diabetes
Kleinert, M., Sylow, L., & Richter, E. A. (2012) · Diabetes Management · doi:10.2217/dmt.12.54 · Cited by 10 · see citing works
Johanns, M., Corbet, C., Jacobs, R., Drappier, M., Bommer, G. T., Herinckx, G., Vertommen, D., Tajeddine, N., Young, D., Messens, J., et al. (2022) · Biochemical Journal · doi:10.1042/bcj20220170 · Cited by 9 · see citing works
Self-citationBizerra, P. F. V., Gilglioni, E. H., Li, H. L., Go, S., Elferink, R. P. J. O., Verhoeven, A. J., & Chang, J. (2023) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/j.bbamcr.2023.119585 · Cited by 9 · see citing works
Al‐Huseini, I., Sirasanagandla, S. R., Babu, K. S., Sofin, R. G. S., & Das, S. (2022) · Current Medicinal Chemistry · doi:10.2174/0929867329666220117114306 · Cited by 8 · see citing works
Cell-specific regulation of iNOS by AMP-activated protein kinase in primary rat hepatocytes
Zhang, B., Lakshmanan, J., Du, Y., Smith, J. W., & Harbrecht, B. G. (2017) · Journal of Surgical Research · doi:10.1016/j.jss.2017.08.028 · Cited by 8 · see citing works
M1-linked ubiquitination by LUBAC regulates AMPK signalling and the response to energetic stress
Elbæk, C. R., Gradinaru, S., Dahlström, A. M., Frueh, A., Jahan, A. S., Cuenco, J., Aalto, A. L., Rizk, J., Hawley, S. A., Franks, S. N. J., et al. (2026) · Cell Death and Differentiation · doi:10.1038/s41418-026-01675-z · Cited by 6 · see citing works
Self-citationAMPK Promotes Larval Metamorphosis of Mytilus coruscus
Zhang, W., Wang, Y., Hu, X., Zhou, Z., Zhu, Y.-T., Xiao, L., & Yang, J.-L. (2022) · Genes · doi:10.3390/genes13122384 · Cited by 6 · see citing works
Autophagy as a therapeutic linchpin in metabolic diseases and obesity-associated diabetes
Vakili, O., Klionsky, D. J., Reiter, R. J., Ren, J., Deshpande, A., Ahn, K. S., Cho, W., Hushmandi, K., & Kumar, A. P. (2026) · Autophagy · doi:10.1080/15548627.2026.2636096 · Cited by 4 · see citing works
AMP-Activated Protein Kinase: A Metabolic Stress Sensor in the Heart
Pelosse, M., Tokarska-Schlattner, M., & Schlattner, U. (2015) · Springer eBooks · doi:10.1007/978-3-319-15263-9_10 · Cited by 4 · see citing works
Stbd1 stimulates AMPK signaling and alleviates insulin resistance in an in vitro hepatocyte model
Theodoulou, A., Speckmann, T., Potamiti, L., Baba, O., Morita, T., Drousiotou, A., Panayiotidis, M. I., Schürmann, A., & Petrou, P. (2025) · FEBS Journal · doi:10.1111/febs.70040 · Cited by 4 · see citing works
Metabolism-associated protein network constructing and host-directed anti-influenza drug repurposing
Tang, H., Jiang, F., Zhang, Z., Yang, J., Li, L., & Zhang, Q. (2025) · Briefings in Bioinformatics · doi:10.1093/bib/bbaf163 · Cited by 4 · see citing works
miR-141/200c contributes to ethanol-mediated hepatic glycogen metabolism
Tran, M., Gilling, S., Wu, J., Wang, L., & Shin, D. (2024) · Molecular Metabolism · doi:10.1016/j.molmet.2024.101942 · Cited by 3 · see citing works
AMPK signaling in cancer: dual roles, molecular mechanisms, and therapeutic potential
Dërmaku‐Sopjani, M., Morina, R., Sermaxhaj, F., Kurti, F., Latifi, J., & Sopjani, M. (2026) · Advances in Medical Sciences · doi:10.1016/j.advms.2026.05.001 · Cited by 2 · see citing works
Exploration of glycogen deposition disorders in low-body-weight fetuses in a pig model
Shao, Y., Bai, M., Wang, S., Wu, Y., Qi, M., Zhang, Y., Peng, C., Xiong, X., Wang, L., Li, Q., et al. (2025) · The Innovation Life · doi:10.59717/j.xinn-life.2024.100119 · Cited by 2 · see citing works
How mass spectrometry can be exploited to study AMPK
Rider, M. H., Vertommen, D., & Johanns, M. (2024) · Essays in Biochemistry · doi:10.1042/ebc20240009 · Cited by 2 · see citing works
Self-citationLKB1/AMPK pathway in the control of hepatic energy metabolism
Viollet, B., & Foretz, M. (2015) · doi:10.1002/9781118663387.ch23 · Cited by 1 · see citing works
Self-citationLaforin: Function and Action of a Glucan Phosphatase
Sherwood, A., Dukhande, V. V., & Gentry, M. S. (2012) · Springer eBooks · doi:10.1007/978-1-4419-0461-4_603 · Cited by 1 · see citing works
Trefts, E. (2019) · Cited by 1 · see citing works
Metabolic and cellular effects of calorie restriction and whey proteins in experimental obesity
Kurki, E. (2013) · Työväentutkimus Vuosikirja
- Authors
- Bultot, L., Guigas, B., Von Wilamowitz-Moellendorff, A., Maisin, L., Vertommen, D., Hussain, N., Beullens, M., Guinovart, J. J., Foretz, M., Viollet, B., Sakamoto, K., Hue, L., & Rider, M. H.
- Affiliations
- de Duve Institute (BE)
- Leiden University Medical Center (NL)
- MRC Protein Phosphorylation Unit, Sir James Black Centre, College of Life Sciences, University of Dundee, Dow Street, Dundee DD1 5EH, Scotland, U.K.
- KU Leuven (BE)
- Institute for Research in Biomedicine (ES)
- Centre National de la Recherche Scientifique (FR)
- INSERM U1016, Institut Cochin, CNRS UMR8104, Université Paris Descartes, Sorbonne Paris Cité, Paris 75014, France
- University of Dundee (GB)
- Corresponding author
- Bultot, Laurent
- Maisin, Liliane
- Vertommen, Didier
- Hussain, Nusrat
- Hue, Louis
- ORCID
- Venue
- Biochemical Journal
- Publisher
- Portland Press Ltd.
- Published
- 2012-03-14
- Volume
- 443
- Issue
- 1
- Pages
- 193-203
- ISSN
- 0264-6021 (ISSN-L)
- 1470-8728
- OpenAlex
- W2075032036
- Cited by
- 131
- References
- 54
- Citations by year
- 2026: 10 · 2025: 6 · 2024: 8 · 2023: 9 · 2022: 10 · 2021: 9 · 2020: 9 · 2019: 11 · 2018: 5 · 2017: 13 · 2016: 8 · 2015: 13 · 2014: 4 · 2013: 10 · 2012: 5
- FWCI
- 4.10
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Biochemical Journal (publishedVersion)
- PubMed (publishedVersion)
- Discovery Research Portal (University of Dundee) (publishedVersion)
- Data Archiving and Networked Services (DANS) (submittedVersion)
- Leiden Repository (Leiden University) (submittedVersion)
- DIAL (Catholic University of Leuven) (submittedVersion)
- Digital Access to Libraries (Université catholique de Louvain (UCL), l'Université de Namur (UNamur) and the Université Saint-Louis (USL-B)) (submittedVersion)
- Lirias (submittedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Metabolism, Diabetes, and Cancer
- Health Sciences › Medicine › Rheumatology › Glycogen Storage Diseases and Myoclonus
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Biochemical and Molecular Research
- Keywords
- AMPK, glycogen synthase, glycogen synthase 1, enzyme inactivation, liver glycogen metabolism, hepatocytes, AICA riboside, A769662, glucagon, UDP-glucose, glucose-6-phosphate
- MeSH terms
- Amino Acid Sequence, Aminoimidazole Carboxamide, Animals, Biphenyl Compounds, Cells, Cultured, Enzyme Activation, Glycogen Synthase, Humans, Liver, Male, Phosphorylation, Protein Processing, Post-Translational, Pyrones, Ribonucleotides, Thiophenes, Consensus Sequence, Rats, Wistar, Cyclic AMP-Dependent Protein Kinases, Mice, Knockout, Apraxia, Ideomotor, Enzyme Activators, Hepatocytes, Mice, Rats, AMP-Activated Protein Kinases
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