Mammalian AMP-activated protein kinase subfamily
Open accessAbstract
The mammalian 5'-AMP-activated protein kinase (AMPK) is related to a growing family of protein kinases in yeast and plants that are regulated by nutritional stress. We find the most prominent expressed form of the hepatic AMPK catalytic subunit (alpha 1) is distinct from the previously cloned kinase subunit (alpha 2). The alpha 1 (548 residues) and alpha 2 (552 residues) isoforms have 90% amino acid sequence identity within the catalytic core but only 61% identity elsewhere. The tissue distribution of the AMPK activity most closely parallels the low abundance 6-kilobase alpha 1 mRNA distribution and the alpha 1 immunoreactivity rather than alpha 2, with substantial amounts in kidney, liver, lung, heart, and brain. Both alpha 1 and alpha 2 isoforms are stimulated by AMP and contain noncatalytic beta and gamma subunits. The liver alpha 1 isoform accounts for approximately 94% of the enzyme activity measured using the SAMS peptide substrate. The tissue distribution of the alpha 2 immunoreactivity parallels the alpha 2 8.5-kilobase mRNA and is most prominent in skeletal muscle, heart, and liver. Isoforms of the beta and gamma subunits present in the human genome sequence reveal that the AMPK consists of a family of isoenzymes.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In humans, each AMPK subunit has multiple distinct isoforms encoded by different genes: α1 and α2 by PRKAA1 and PRKAA2; β1 and β2 by PRKAB1 and PRKAB2; γ1, γ2, and γ3 by PRKAG1, PRKAG2, and PRKAG3.
“In humans, each subunit has multiple distinct isoforms encoded by different genes: the α-subunit has two isoforms, α1 and α2, encoded by gene PRKAA1 and PRKAA2, respectively [20]; the β-subunit has two isoforms, β1 and β2, encoded by gene PRKAB1 and PRKAB2, respectively [21]; and the γ-subunit has three isoforms, γ1, γ2, and γ3, encoded by gene PRKAG1, PRKAG2, and PRKAG3, respectively [22].”
From AMPK, Mitochondrial Function, and Cardiovascular Disease (2020) · cites this paper as [20]
Cites
PROTEIN MEASUREMENT WITH THE FOLIN PHENOL REAGENT
Lowry, O. H., Rosebrough, N., Farr, A. L., & Randall, R. (1951) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)52451-6 · Cited by 315,771 · see citing works
Cleavage of Structural Proteins during the Assembly of the Head of Bacteriophage T4
LAEMMLI, U. K. (1970) · Nature · doi:10.1038/227680a0 · Cited by 249,961 · see citing works
Hanks, S. K., & Hunter, T. R. (1995) · PubMed · Cited by 2,518 · see citing works
The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and classification 1
Hanks, S. K., & Hunter, T. (1995) · The FASEB Journal · doi:10.1096/fasebj.9.8.7768349 · Cited by 2,361 · see citing works
Knighton, D. R., Zheng, J., Eyck, L. F. T., Ashford, V. A., Xuong, N., Taylor, S. S., & Sowadski, J. M. (1991) · Science · doi:10.1126/science.1862342 · Cited by 1,764 · see citing works
Guo, S., & Kemphues, K. J. (1995) · Cell · doi:10.1016/0092-8674(95)90082-9 · Cited by 1,113 · see citing works
A Yeast Gene That Is Essential for Release from Glucose Repression Encodes a Protein Kinase
Celenza, J. L., & Carlson, M. (1986) · Science · doi:10.1126/science.3526554 · Cited by 688 · see citing works
Carling, D., Zammit, V. A., & Hardie, D. G. (1987) · FEBS Letters · doi:10.1016/0014-5793(87)80292-2 · Cited by 599 · see citing works
Kudo, N., Barr, A., Barr, R. L., Desai, S. S., & Lopaschuk, G. D. (1995) · Journal of Biological Chemistry · doi:10.1074/jbc.270.29.17513 · Cited by 565 · see citing works
DAVIES, S. P., Carling, D., & Hardie, D. G. (1989) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1989.tb15185.x · Cited by 431 · see citing works
Role of the AMP-activated protein kinase in the cellular stress response
Corton, J. M., Gillespie, J. G., & Hardie, D. G. (1994) · Current Biology · doi:10.1016/s0960-9822(00)00070-1 · Cited by 423 · see citing works
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 405 · see citing works
Acetyl-CoA carboxylase regulation of fatty acid oxidation in the heart.
Saddik, M., Gamble, J., Witters, L. A., & Lopaschuk, G. D. (1993) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)74465-2 · Cited by 390 · see citing works
Self-citationMitchelhill, 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 · see citing works
Self-citationPhosphorylation of bovine hormone‐sensitive lipase by the AMP‐activated protein kinase
Garton, A. J., Campbell, D. G., Carling, D., Hardie, D. G., Colbran, R. J., & Yeaman, S. J. (1989) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1989.tb14548.x · Cited by 271 · see citing works
Carling, D., Aguan, K., Woods, A., Verhoeven, A., Beri, R. K., Brennan, C. H., Sidebottom, C., Davison, M. D., & Scott, J. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)78143-5 · Cited by 253 · see citing works
Yang, X., Jiang, R., & Carlson, M. (1994) · The EMBO Journal · doi:10.1002/j.1460-2075.1994.tb06933.x · Cited by 141 · see citing works
Stapleton, D., Gao, G., Michell, B. J., Widmer, J., Mitchelhill, K. I., Teh, T., House, C. M., Witters, L. A., & Kemp, B. E. (1994) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)43879-3 · Cited by 122 · see citing works
Self-citationFerrer, A., Caelles, C., Massot, N., & Hegardt, F. G. (1985) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(85)91161-1 · Cited by 118 · see citing works
Gao, G., Widmer, J., Stapleton, D., Teh, T., Cox, T. M., Kemp, B. E., & Witters, L. A. (1995) · Biochimica et Biophysica Acta (BBA) - Molecular Cell Research · doi:10.1016/0167-4889(94)00222-z · Cited by 82 · see citing works
Self-citationVerhoeven, A. J. M., Woods, A., Brennan, C. H., et al. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.tb20255.x · Cited by 61 · see citing works
Watford, M. (1994) · Biochimica et Biophysica Acta (BBA) - General Subjects · doi:10.1016/0304-4165(94)90029-9 · Cited by 58 · see citing works
Characterization of a novel murine testis-specific serine/threonine kinase
Bielke, W., Blaschke, R., Miescher, G. C., et al. (1994) · Gene · doi:10.1016/0378-1119(94)90762-5 · Cited by 54 · see citing works
Verhoeven, A. J. M., Woods, A., Brennan, C. H., et al. (1995) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1995.0236n.x · Cited by 50 · see citing works
Glucose regulation of acetyl-CoA carboxylase in hepatoma and islet cells.
Louis, N. A., & Witters, L. A. (1992) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(18)45876-0 · Cited by 44 · see citing works
Self-citationMolecular cloning, expression and chromosomal localisation of human AMP‐activated protein kinase
Beri, R. K., Marley, A. E., See, C. G., et al. (1994) · FEBS Letters · doi:10.1016/0014-5793(94)01247-4 · Cited by 42 · see citing works
Aguan, K., Scott, J., See, C. G., et al. (1994) · Gene · doi:10.1016/0378-1119(94)90174-0 · Cited by 36 · see citing works
Yeast acetyl-CoA carboxylase: In vitro phosphorylation by mammalian and yeast protein kinases
Witters, L. A., & Watts, T. D. (1990) · Biochemical and Biophysical Research Communications · doi:10.1016/0006-291x(90)90341-j · Cited by 32 · see citing works
Self-citationSpreadsheet macros for coloring sequence alignments.
Haygood, M. G. (1993) · PubMed · Cited by 17 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
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 · see citing works
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 · see citing works
Metformin is an AMP kinase-dependent growth inhibitor for breast cancer cells
Zakikhani, M., Dowling, R., Fantus, I. G., Sonenberg, N., & Pollak, M. (2006) · Cancer Research · doi:10.1158/0008-5472.can-06-1500 · Cited by 1,048 · see citing works
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 · see citing works
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 · see citing works
Musi, N., Hirshman, M. F., Nygren, J., Svanfeldt, M., Bavenholm, P., Rooyackers, O., Zhou, G., Williamson, J. M., Ljunqvist, O., Efendic, S., et al. (2002) · Diabetes · doi:10.2337/diabetes.51.7.2074 · Cited by 806 · see citing works
AMP-activated protein kinase-deficient mice are resistant to the metabolic effects of resveratrol
Um, J.-H., Park, S.-J., Kang, H., Yang, S., Foretz, M., McBurney, M. W., Kim, M. K., Viollet, B., & Chung, J. H. (2010) · Diabetes · doi:10.2337/db09-0482 · Cited by 647 · see citing works
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 · see citing works
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 · see citing works
Wojtaszewski, J. F. P., Nielsen, P., Hansen, B. F., Richter, E. A., & Kiens, B. (2000) · The Journal of Physiology · doi:10.1111/j.1469-7793.2000.t01-1-00221.x · Cited by 435 · see citing works
AMPK β Subunit Targets Metabolic Stress Sensing to Glycogen
Polekhina, G., Gupta, A., Michell, B. J., van Denderen, B., Murthy, S., Feil, S. C., Jennings, I. G., Campbell, D. J., Witters, L. A., Parker, M. W., et al. (2003) · Current Biology · doi:10.1016/s0960-9822(03)00292-6 · Cited by 423 · see citing works
Self-citationContraction-induced Changes in Acetyl-CoA Carboxylase and 5′-AMP-activated Kinase in Skeletal Muscle
Vavvas, D., Apazidis, A., Saha, A. K., Gamble, J., Patel, A., Kemp, B. E., Witters, L. A., & Ruderman, N. B. (1997) · Journal of Biological Chemistry · doi:10.1074/jbc.272.20.13255 · Cited by 395 · see citing works
Self-citation<scp>AMP</scp> ‐activated protein kinase: a cellular energy sensor that comes in 12 flavours
Ross, F. A., MacKintosh, C., & Hardie, D. G. (2016) · The FEBS Journal · doi:10.1111/febs.13698 · Cited by 381 · see citing works
Musi, N., Fujii, N., Hirshman, M. F., Ekberg, I., Fröberg, S., Ljungqvist, O., Thorell, A., & Goodyear, L. J. (2001) · Diabetes · doi:10.2337/diabetes.50.5.921 · Cited by 371 · see citing works
Fujii, N., Hayashi, T., Hirshman, M. F., Smith, J. T., Habinowski, S. A., Kaijser, L., Mu, J., Ljungqvist, O., Birnbaum, M. J., Witters, L. A., et al. (2000) · Biochemical and Biophysical Research Communications · doi:10.1006/bbrc.2000.3073 · Cited by 351 · see citing works
AMP-Activated Protein Kinase: An Ultrasensitive System for Monitoring Cellular Energy Charge
HARDIE, D. G., SALT, I. P., HAWLEY, S. A., & DAVIES, S. P. (1999) · Biochemical Journal · doi:10.1042/bj3380717 · Cited by 362 · see citing works
Wojtaszewski, J. F. P., MacDonald, C., Nielsen, J. N., Hellsten, Y., Hardie, D. G., Kemp, B. E., Kiens, B., & Richter, E. A. (2003) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00436.2002 · Cited by 348 · see citing works
Self-citationCulmsee, C., monnig, J., Kemp, B. E., & Mattson, M. P. (2001) · Journal of Molecular Neuroscience · doi:10.1385/jmn:17:1:45 · Cited by 340 · see citing works
Self-citationThe 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 · see citing works
AMPK, Mitochondrial Function, and Cardiovascular Disease
Wu, S., & Zou, M.-H. (2020) · International Journal of Molecular Sciences · doi:10.3390/ijms21144987 · Cited by 286 · see citing works
Xie, Z., Dong, Y., Scholz, R., Neumann, D., & Zou, M.-H. (2008) · Circulation · doi:10.1161/circulationaha.107.744490 · Cited by 273 · see citing works
Um, J. H., Yang, S., Yamazaki, S., Kang, H., Viollet, B., Foretz, M., & Chung, J. H. (2007) · Journal of Biological Chemistry · doi:10.1074/jbc.c700070200 · Cited by 244 · see citing works
Emerging Role of cAMP/AMPK Signaling
Aslam, M., & Ladilov, Y. (2022) · Cells · doi:10.3390/cells11020308 · Cited by 241 · see citing works
Thornton, C., Snowden, M. A., & Carling, D. (1998) · Journal of Biological Chemistry · doi:10.1074/jbc.273.20.12443 · Cited by 240 · see citing works
Winder, W. W., Wilson, H. A., Hardie, D. G., Rasmussen, B. B., Hutber, C. A., Call, G. B., Clayton, R. D., Conley, L. M., Yoon, S., & Zhou, B. (1997) · Journal of Applied Physiology · doi:10.1152/jappl.1997.82.1.219 · Cited by 237 · see citing works
The Regulation of Fat Metabolism during Aerobic Exercise
Muscella, A., Stefàno, E., Lunetti, P., Capobianco, L., & Marsigliante, S. (2020) · Biomolecules · doi:10.3390/biom10121699 · Cited by 237 · see citing works
Koh, H.-J., Arnolds, D. E., Fujii, N., Tran, T. T., Rogers, M. J., Jessen, N., Li, Y., Liew, C. W., Ho, R. C., Hirshman, M. F., et al. (2006) · Molecular and Cellular Biology · doi:10.1128/mcb.00979-06 · Cited by 202 · see citing works
AMPK β1 Deletion Reduces Appetite, Preventing Obesity and Hepatic Insulin Resistance
Dzamko, N., van Denderen, B. J. W., Hevener, A. L., Jørgensen, S. B., Honeyman, J., Galic, S., Chen, Z.-P., Watt, M. J., Campbell, D. J., Steinberg, G. R., et al. (2010) · Journal of Biological Chemistry · doi:10.1074/jbc.m109.056762 · Cited by 175 · see citing works
Self-citationDifferential regulation by AMP and ADP of AMPK complexes containing different γ subunit isoforms
Ross, F. A., Jensen, T. E., & Hardie, D. G. (2016) · Biochemical Journal · doi:10.1042/bj20150910 · Cited by 172 · see citing works
Wojtaszewski, J. F. P., Birk, J. B., Frøsig, C., Holten, M., Pilegaard, H., & Dela, F. (2005) · The Journal of Physiology · doi:10.1113/jphysiol.2005.082669 · Cited by 170 · see citing works
Frøsig, C., Jørgensen, S. B., Hardie, D. G., Richter, E. A., & Wojtaszewski, J. F. P. (2004) · American Journal of Physiology-Endocrinology and Metabolism · doi:10.1152/ajpendo.00317.2003 · Cited by 161 · see citing works
Cellular Metabolism in Lung Health and Disease
Liu, G., & Summer, R. (2019) · Annual Review of Physiology · doi:10.1146/annurev-physiol-020518-114640 · Cited by 157 · see citing works
Obesity Impairs Skeletal Muscle Regeneration Through Inhibition of AMPK
Fu, X., Zhu, M., Zhang, S., Foretz, M., Viollet, B., & Du, M. (2016) · Diabetes · doi:10.2337/db15-0647 · Cited by 155 · see citing works
“subunit and two isoforms, a1 and a2 (19).”
BackgroundMeng, S., Cao, J., He, Q., Xiong, L., Chang, E., Radovick, S., Wondisford, F. E., & He, L. (2015) · Journal of Biological Chemistry · doi:10.1074/jbc.m114.604421 · Cited by 146 · see citing works
Exercise-induced AMPK activity in skeletal muscle: Role in glucose uptake and insulin sensitivity
Friedrichsen, M., Mortensen, B., Pehmøller, C., Birk, J. B., & Wojtaszewski, J. F. P. (2013) · Molecular and Cellular Endocrinology · doi:10.1016/j.mce.2012.06.013 · Cited by 143 · see citing works
AMP-activated protein kinase deficiency exacerbates aging-induced myocardial contractile dysfunction
Turdi, S., Fan, X., Li, J., Zhao, J., Huff, A. F., Du, M., & Ren, J. (2010) · Aging Cell · doi:10.1111/j.1474-9726.2010.00586.x · Cited by 141 · see citing works
Williams, T., Courchet, J., Viollet, B., Brenman, J. E., & Polleux, F. (2011) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.1013660108 · Cited by 123 · see citing works
Gusarova, G. A., Dada, L. A., Kelly, A. M., Brodie, C., Witters, L. A., Chandel, N. S., & Sznajder, J. I. (2009) · Molecular and Cellular Biology · doi:10.1128/mcb.00054-09 · Cited by 118 · see citing works
Self-citationLKB1 and AMPK and the regulation of skeletal muscle metabolism
Koh, H.-J., Brandauer, J., & Goodyear, L. J. (2008) · Current Opinion in Clinical Nutrition and Metabolic Care · doi:10.1097/mco.0b013e3282fb7b76 · Cited by 78 · see citing works
Cao, Y., Bojjireddy, N., Kim, M., Li, T., Zhai, P., Nagarajan, N., Sadoshima, J., Palmiter, R. D., & Tian, R. (2017) · Circulation Research · doi:10.1161/circresaha.117.311159 · Cited by 74 · see citing works
Lee, K. M., Yang, S.-J., Kim, Y. D., Choi, Y. D., Nam, J. H., Choi, C. S., Choi, H.-S., & Park, C.-S. (2013) · Diabetes · doi:10.2337/db12-1030 · Cited by 77 · see citing works
Akerstrom, T. C. A., Birk, J. B., Klein, D. K., Erikstrup, C., Plomgaard, P., Pedersen, B. K., & Wojtaszewski, J. F. P. (2006) · Biochemical and Biophysical Research Communications · doi:10.1016/j.bbrc.2006.02.057 · Cited by 75 · see citing works
Miyamoto, L., Toyoda, T., Hayashi, T., Yonemitsu, S., Nakano, M., Tanaka, S., Ebihara, K., Masuzaki, H., Hosoda, K., Ogawa, Y., et al. (2007) · Journal of Applied Physiology · doi:10.1152/japplphysiol.01034.2006 · Cited by 72 · see citing works
AMPK negatively regulates RANKL-induced osteoclast differentiation by controlling oxidative stress
Tanaka, M., Inoue, H., Takahashi, N., & Uehara, M. (2023) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2023.05.033 · Cited by 41 · see citing works
Chen, Y., Zhang, H., Liu, H., Li, K., & Su, X. (2018) · Microvascular Research · doi:10.1016/j.mvr.2018.03.010 · Cited by 19 · see citing works
- Authors
- Stapleton, D., Mitchelhill, K. I., Gao, G., Widmer, J., Michell, B. J., Teh, T., House, C. M., Fernandez, C. S., Cox, T., Witters, L. A., & Kemp, B. E.
- Affiliations
- St Vincents Institute of Medical Research (AU)
- Dartmouth College (US)
- Corresponding author
- Kemp, Bruce E.
- Venue
- Journal of Biological Chemistry
- Publisher
- Elsevier BV
- Published
- 1996-01
- Volume
- 271
- Issue
- 2
- Pages
- 611-614
- ISSN
- 0021-9258 (ISSN-L)
- OpenAlex
- W2170880090
- Cited by
- 652
- References
- 29
- Citations by year
- 2026: 13 · 2025: 13 · 2024: 10 · 2023: 18 · 2022: 20 · 2021: 23 · 2020: 20 · 2019: 21 · 2018: 28 · 2017: 25 · 2016: 30 · 2015: 31 · 2014: 36 · 2013: 25 · 2012: 41
- FWCI
- 4.55
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- Locations
- Journal of Biological Chemistry (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (DK-35712, R01DK035712)
- 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 › Peroxisome Proliferator-Activated Receptors
- Keywords
- AMPK, isozymes, tissue distribution, nutritional stress, liver, skeletal muscle, gene expression
- MeSH terms
- Amino Acid Sequence, Animals, Humans, Molecular Sequence Data, Organ Specificity, RNA, Messenger, Species Specificity, Swine, Sequence Alignment, Protein Serine-Threonine Kinases, Sequence Analysis, Rats
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