AMPK signalling in health and disease

Current Opinion in Cell Biology

Volumn 45, Issue , 2017, Pages 31-37

  Carling, David ^a  

^a HAMMERSMITH HOSPITAL   (United Kingdom)

Author keywords

[No Author keywords available]

Indexed keywords

ENZYME ACTIVATOR; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE;

ENZYME PHOSPHORYLATION; HEALTH; HUMAN; METABOLIC DISORDER; MOUSE MODEL; NONHUMAN; PRIORITY JOURNAL; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; SPECIES; ANIMAL; ANTAGONISTS AND INHIBITORS; CHEMISTRY; ENERGY METABOLISM; HOMEOSTASIS; METABOLIC DISEASES; METABOLISM; NEOPLASMS;

AMP-ACTIVATED PROTEIN KINASES; ANIMALS; ENERGY METABOLISM; HOMEOSTASIS; HUMANS; METABOLIC DISEASES; NEOPLASMS; SIGNAL TRANSDUCTION;

EID: 85013230596     PISSN: 09550674     EISSN: 18790410     Source Type: Journal    
DOI: 10.1016/j.ceb.2017.01.005     Document Type: Review

References (51)

1. 1 Boyer, P.D., Chance, B., Ernster, L., Mitchell, P., Racker, E., Slater, E.C., Oxidative phosphorylation and photophosphorylation. Annu Rev Biochem 46 (1977), 955–1026.
2. 2 Carling, D., Thornton, C., Woods, A., Sanders, M.J., AMP-activated protein kinase: new regulation, new roles?. Biochem J 445 (2012), 11–27.
3. 3 Cool, B., Zinker, B., Chiou, W., Kifle, L., Cao, N., Perham, M., Dickinson, R., Adler, A., Gagne, G., Iyengar, R., et al. Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab 3 (2006), 403–416.
4. 4 Giordanetto, F., Karis, D., Direct AMP-activated protein kinase activators: a review of evidence from the patent literature. Exprt Opin Ther Pat 22 (2012), 1467–1477.
5. 5 Xiao, B., Sanders, M.J., Carmena, D., Bright, N.J., Haire, L.F., Underwood, E., Patel, B.R., Heath, R.B., Walker, P.A., Hallen, S., et al. Structural basis of AMPK regulation by small molecule activators. Nat Commun, 4, 2013, 3017.
6. 6 Carling, D., Mayer, F.V., Sanders, M.J., Gamblin, S.J., AMP-activated protein kinase: nature's energy sensor. Nat Chem Biol 7 (2011), 512–518.
7. 7 Hardie, D.G., Schaffer, B.E., Brunet, A., AMPK: an energy-sensing pathway with multiple inputs and outputs. Trends Cell Biol 26 (2016), 190–201.
8. 8 Steinberg, G.R., Kemp, B.E., AMPK in health and disease. Physiol Rev 89 (2009), 1025–1078.
9. 9 Arad, M., Benson, D.W., Perez-Atayde, A.R., McKenna, W.J., Sparks, E.A., Kanter, R.J., McGarry, K., Seidman, J.G., Seidman, C.E., Constitutively active AMP kinase mutations cause glycogen storage disease mimicking hypertrophic cardiomyopathy. J Clin Invest 109 (2002), 357–362.
10. 10 Blair, E., Redwood, C., Ashrafian, H., Ostman-Smith, I., Watkins, H., Mutations in the g2 subunit of AMP-activated protein kinase cause familial hypertrophic cardiomyopathy: evidence for the central role of energy compromise in disease pathogenesis. Hum Mol Genet 10 (2001), 1215–1220.
11. 11 Gollob, M.H., Green, M.S., Tang, A.S.L., Gollob, T., Karibe, A., Hassan, A., Ahmad, F., Lozado, R., Shah, G., Fananapazir, L., et al. Identification of a gene responsible for familial Wolff-Parkinson-White syndrome. New Engl J Med 344 (2001), 1823–1831.
12. 12 Gollob, M.H., Seger, J.J., Gollob, T.N., Tapscott, T., Gonzales, O., Bachiniski, L., Roberts, R., Novel PRKAG2 mutation responsible for the genetic syndrome of ventricular preexcitation and conduction system disease with childhood onset and absence of cardiac hypertrophy. Circulation 104 (2001), 3030–3033.
13. 13 Milan, D., Jeon, J.T., Looft, C., Amarger, V., Robic, A., Thelander, M., Rogel-Gaillard, C., Paul, S., Iannuccelli, N., Rask, L., et al. A mutation in PRKAG3 associated with excess glycogen content in pig skeletal muscle. Science 288 (2000), 1248–1251.
14. 14 Cheung, P.C.F., Salt, I.P., Davies, S.P., Hardie, D.G., Carling, D., Characterization of AMP-activated protein kinase γ-subunit isoforms and their role in AMP binding. Biochem J 346 (2000), 659–669.
15. 15•• Yavari, A., Stocker, C.J., Ghaffari, S., Wargent, E.T., Steeples, V., Czibik, G., Pinter, K., Bellahcene, M., Woods, A., Martinez de Morentin, P.B., et al. Chronic activation of gamma2 AMPK induces obesity and reduces beta cell function. Cell Metab 23 (2016), 821–836 This study reports that mice expressing γ2 harbouring R302Q mutation are hyperphagic and develop adult-onset obesity and impaired glucose homeostasis.
16. 16•• Yang, X., Mudgett, J., Bou-About, G., Champy, M.F., Jacobs, H., Monassier, L., Pavlovic, G., Sorg, T., Herault, Y., Petit-Demouliere, B., et al. Physiological expression of AMPKγ2RG mutation causes Wolff-Parkinson-White Syndrome and induces kidney injury in mice. J Biol Chem 291 (2016), 23428–23439 Describes the phenotype of two mouse lines (expressing γ2 with either N488I or R531G mutation). Both lines are protected against high fat diet-induced obesity. A very mild cardiac phenotype is reported (much less severe than the human disease) and the R531G line develops kidney cysts and impaired kidney function.
17. 17 Mahlapuu, M., Johansson, C., Lindgren, K., Hjalm, G., Barnes, B.R., Krook, A., Zierath, J.R., Andersson, L., Marklund, S., Expression profiling of the gamma-subunit isoforms of AMP-activated protein kinase suggests a major role for gamma3 in white skeletal muscle. Am J Physiol Endocrinol Metab 286 (2004), E194–200.
18. 18 Bultot, L., Jensen, T.E., Lai, Y.C., Madsen, A.L., Collodet, C., Kviklyte, S., Deak, M., Yavari, A., Foretz, M., Ghaffar, i. S., et al. Benzimidazole derivative small-molecule 991 enhances AMPK activity and glucose uptake induced by AICAR or contraction in skeletal muscle. Am J Physiol 311 (2016), E706–E719.
19. 19 Arad, M., Moskowitz, I.P., Patel, V.V., Ahmad, F., Perez-Atayde, A.R., Sawyer, D.B., Walter, M., Li, G.H., Burgon, P.G., Maguire, C.T., et al. Transgenic mice overexpressing mutant PRKAG2 define the cause of Wolff-Parkinson-White Syndrome in glycogenstorage cardiomyopathy. Circulation 107 (2003), 2850–2856.
20. 20 Davies, J.K., Wells, D.J., Liu, K., Whitrow, H.R., Daniel, T.D., Grignani, R., Lygate, C.A., Schneider, J.E., Noel, G., Watkins, H., Carling, D., Characterization of the role of gamma2 R531G mutation in AMP-activated protein kinase in cardiac hypertrophy and Wolff-Parkinson-White syndrome. Am J Physiol Heart Circ Physiol 290 (2006), H1942–1951.
21. 21 Sidhu, J.S., Rajawat, Y.S., Rami, T.G., Gollob, M.H., Wang, Z., Yuan, R., Marian, A.J., DeMayo, F.J., Weilbacher, D., Taffet, G.E., et al. Transgenic mouse model of ventricular preexcitation and atrioventricular reentrant tachycardia induced by an AMP-activated protein kinase loss-of-function mutation responsible for Wolff-Parkinson-White syndrome. Circulation 111 (2005), 21–29.
22. 22 Hawley, S.A., Davison, M., Woods, A., Davies, S.P., Beri, R.K., Carling, D., Hardie, D.G., Characterization of the AMP-activated protein kinase kinase from rat liver and identification of threonine 172 as the major site at which it phosphorylates AMP-activated protein kinase. J Biol Chem 271 (1996), 27879–27887.
23. 23 Hawley, S.A., Boudeau, J., Reid, J.L., Mustard, K.J., Udd, L., Makela, T.P., Alessi, D.R., Hardie, D.G., Complexes between the LKB1 tumor suppressor, STRAD alpha/beta and MO25 alpha/beta are upstream kinases in the AMP-activated protein kinase cascade. J Biol, 2, 2003, 28.
24. 24 Hawley, S.A., Pan, D.A., Mustard, K.J., Ross, L., Bain, J., Edelman, A.M., Frenguelli, B.G., Hardie, D.G., Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab 2 (2005), 9–19.
25. 25 Woods, A., Dickerson, K., Heath, R., Hong, S.P., Momcilovic, M., Johnstone, S.R., Carlson, M., Carling, D., Ca2+/calmodulin-dependent protein kinase kinase-beta acts upstream of AMP-activated protein kinase in mammalian cells. Cell Metab 2 (2005), 21–33.
26. 26 Woods, A., Johnstone, S.R., Dickerson, K., Leiper, F.C., Fryer, L.G., Neumann, D., Schlattner, U., Wallimann, T., Carlson, M., Carling, D., LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr Biol 13 (2003), 2004–2008.
27. 27 Sanders, M.J., Grondin, P.O., Hegarty, B.D., Snowden, M.A., Carling, D., Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade. Biochem J 403 (2007), 139–148.
28. 28 Suter, M., Riek, U., Tuerk, R., Schlattner, U., Wallimann, T., Neumann, D., Dissecting the role of AMP for allosteric stimulation, activation and deactivation of AMP-activated protein kinase. J Biol Chem 281 (2006), 32207–32216.
29. 29 Davies, S.P., Helps, N.R., Cohen, P.T., Hardie, D.G., 5′-AMP inhibits dephosphorylation, as well as promoting phosphorylation, of the AMP-activated protein kinase. Studies using bacterially expressed human protein phosphatase-2C alpha and native bovine protein phosphatase-2AC. FEBS Lett 377 (1995), 421–425.
30. 30 Zadra, G., Photopoulos, C., Tyekucheva, S., Heidari, P., Weng, Q.P., Fedele, G., Liu, H., Scaglia, N., Priolo, C., Sicinska, E., et al. A novel direct activator of AMPK inhibits prostate cancer growth by blocking lipogenesis. EMBO Mol Med 6 (2014), 519–538.
31. 31 Goransson, O., McBride, A., Hawley, S.A., Ross, F.A., Shpiro, N., Foretz, M., Viollet, B., Hardie, D.G., Sakamoto, K., Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. J Biol Chem 282 (2007), 32549–32560.
32. 32 Sanders, M.J., Ali, Z.S., Hegarty, B.D., Heath, R., Snowden, M.A., Carling, D., Defining the mechanism of activation of AMP-activated protein kinase by the small molecule A-769662, a member of the thienopyridone family. J Biol Chem 282 (2007), 32539–32548.
33. 33• Rajamohan, F., Reyes, A.R., Frisbie, R.K., Hoth, L.R., Sahasrabudhe, P., Magyar, R., Landro, J.A., Withka, J.M., Caspers, N.L., Calabrese, M.F., et al. Probing the enzyme kinetics, allosteric modulation and activation of α1- and α2-subunit-containing AMP-activated protein kinase (AMPK) heterotrimeric complexes by pharmacological and physiological activators. Biochem J 473 (2016), 581–592 Reports the effects of different AMPK subunit isoforms on activation of AMPK complexes by nucleotides and A769662.
34. 34• Ross, F.A., Jensen, T.E., Hardie, D.G., Differential regulation by AMP and ADP of AMPK complexes containing different gamma subunit isoforms. Biochem J 473 (2016), 189–199 Reports the effects of different γ subunit isoforms on AMPK regulation by nucleotides. The findings suggest that the γ isoforms could play a physiological role in regulating AMPK activity.
35. 35 Xiao, B., Sanders, M.J., Underwood, E., Heath, R., Mayer, F., Carmena, D.J., Jing, C., Walker, P.A., Eccleston, J.E., Haire, L.F., et al. Structure of mammalian AMPK and its regulation by ADP. Nature 472 (2011), 230–233.
36. 36 Xin, F.J., Wang, J., Zhao, R.Q., Wang, Z.X., Wu, J.W., Coordinated regulation of AMPK activity by multiple elements in the a subunit. Cell Res 23 (2013), 1237–1240.
37. 37 Oakhill, J.S., Stell, R., Chen, Z.P., Scott, J.W., Ling, N., Tam, S., Kemp, B.E., AMPK is a direct adenylate charge-regulated protein kinase. Science 332 (2011), 1433–1435.
38. 38 Gowans, G.J., Hawley, S.A., Ross, F.A., Hardie, D.G., AMP is a true physiological regulator of AMP-activated protein kinase by both allosteric activation and enhancing net phosphorylation. Cell Metab 18 (2013), 556–566.
39. 39 Zhang, Y.L., Guo, H., Zhang, C.S., Lin, S.Y., Yin, Z., Peng, Y., Luo, H., Shi, Y., Lian, G., Zhang, C., et al. AMP as a low-energy charge signal autonomously initiates assembly of AXIN-AMPK-LKB1 complex for AMPK activation. Cell Metab 18 (2013), 546–555.
40. 40•• Zhang, C.S., Li, M., Ma, T., Zong, Y., Cui, J., Feng, J.W., Wu, Y.Q., Lin, S.Y., Lin, S.C., Metformin activates AMPK through the lysosomal pathway. Cell Metab 24 (2016), 521–522 A short paper that reports that axin is required for the activation of AMPK in liver by metformin in vivo.
41. 41 Hurley, R.L., Anderson, K.A., Franzone, J.M., Kemp, B.E., Means, A.R., Witters, L.A., The Ca2+/calmodulin-dependent protein kinase kinases are AMP-activated protein kinase kinases. J Biol Chem 280 (2005), 29060–29066.
42. 42 Stahmann, N., Woods, A., Carling, D., Heller, R., Thrombin activates AMP-activated protein kinase in endothelial cells via a pathway involving Ca2+/calmodulin-dependent protein kinase kinase beta. Mol Cell Biol 26 (2006), 5933–5945.
43. 43 Scott, J.W., van Denderen, B.J., Jorgensen, S.B., Honeyman, J.E., Steinberg, G.R., Oakhill, J.S., Iseli, T.J., Koay, A., Gooley, P.R., Stapleton, D., Kemp, B.E., Thienopyridone drugs are selective activators of AMP-activated protin kinase beta1-containing complexes. Chem Biol 15 (2008), 1220–1230.
44. 44 Lai, Y.C., Kviklyte, S., Vertommen, D., Lantier, L., Foretz, M., Viollet, B., Hallén, S., Rider, M.H., A small-molecule benzimidazole derivative that potently activates AMPK to increase glucose transport in skeletal muscle: comparison with effects of contraction and other AMPK activators. Biochem J 460 (2014), 363–375.
45. 45• Cameron, K.O., Kung, D.W., Kalgutkar, A.S., Kurumbail, R.G., Miller, R., Salatto, C.T., Ward, J., Withka, J.M., Bhattacharya, S.K., Boehm, M., et al. Discovery and preclinical characterization of 6-chloro-5-[4-(1-hydroxycyclobutyl)phenyl]-1H-indole-3-carboxylic acid (PF-06409577), a direct activator of adenosine monophosphate-activated protein kinase (AMPK), for the potential treatment of diabetic nephropathy. J Med Chem 59 (2016), 8068–8081 Identifies a novel AMPK activator that shows marked selectivity for β1-containing AMPK complexes.
46. 46 Calabrese, M.F., Rajamohan, F., Harris, M.S., Caspers, N.L., Magyar, R., Withka, J.M., Wang, H., Borzilleri, K.A., Sahasrabudhe, P.V., Hoth, L.R., et al. Structural basis for AMPK activation: natural and synthetic ligands regulate kinase activity from opposite poles by different molecular mechanisms. Structure 22 (2014), 1161–1172.
47. 47 Mitchelhill, K., Michell, B., House, C., Stapleton, D., Dyck, J., Gamble, J., Ullrich, C., LA, W., Kemp, B., Posttranslational modifications of the 5′-AMP-activated protein kinase β1 subunit. J Biol Chem 272 (1997), 24475–24479.
48. 48 Woods, A., Vertommen, D., Neumann, D., Turk, R., Bayliss, J., Schlattner, U., Wallimann, T., Carling, D., Rider, M.H., Identification of phosphorylation sites in AMP-activated protein kinase (AMPK) for upstream AMPK kinases and study of their roles by site-directed mutagenesis. J Biol Chem 278 (2003), 28434–28442.
49. 49 Scott, J.W., Ling, N., Issa, S.M., Dite, T.A., O'Brien, M.T., Chen, Z.P., Galic, S., Langendorf, C.G., Steinberg, G.R., Kemp, B.E., Oakhill, J.S., Small molecule drug A-769662 and AMP synergistically activate naive AMPK independent of upstream kinase signaling. Chem Biol 21 (2014), 619–627.
50. 50 Endicott, J.A., Noble, M.E., Johnson, L.N., The structural basis for control of eukaryotic protein kinases. Annu Rev Biochem 81 (2012), 587–613.
51. 51 Murphy, R.T., Mogensen, J., McGarry, K., Bahl, A., Evans, A., Osman, E., Syrris, P., Gorman, G., Farrell, M., Holton, J.L., et al. Adenosine monophosphate-activated protein kinase disease mimicks hypertrophic cardiomyopathy and Wolff-Parkinson-White syndrome: natural history. J Am Coll Cardiol 45 (2005), 922–930.