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

Biochemical Journal

Volumn 473, Issue 5, 2016, Pages 581-592

  Rajamohan, Francis ^a   Reyes, Allan R ^b   Frisbie, Richard K ^a   Hoth, Lise R ^a   Sahasrabudhe, Parag ^a   Magyar, Rachelle ^a   Landro, James A ^b   Withka, Jane M ^a   Caspers, Nicole L ^a   Calabrese, Matthew F ^a   Ward, Jessica ^b   Kurumbail, Ravi G ^a  

^a PFIZER GLOBAL RESEARCH AND DEVELOPMENT   (United States)

^b PFIZER INC   (United States)

Author keywords

Allosteric activation; AMP activated protein kinase (ampk); Heterotrimeric complex; Kinase activity; Metabolic sensor; Recombinant protein.

Indexed keywords

6,7 DIHYDRO 4 HYDROXY 3 (2' HYDROXY 1,1' BIPHENYL 4 YL) 6 OXOTHIENO[2,3 B]PYRIDINE 5 CARBONITRILE; ADENOSINE DIPHOSPHATE; ADENOSINE PHOSPHATE; ADENOSINE TRIPHOSPHATE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; ENZYME ACTIVATOR; ISOENZYME; PRKAA1 PROTEIN, HUMAN; PRKAB2 PROTEIN, HUMAN; PROTEIN SUBUNIT; PYRONE DERIVATIVE; RECOMBINANT PROTEIN; THIOPHENE DERIVATIVE;

ALLOSTERISM; ANIMAL TISSUE; ARTICLE; BINDING AFFINITY; COMPARATIVE STUDY; ENZYME ACTIVATION; ENZYME ACTIVE SITE; ENZYME KINETICS; IMMUNOBLOTTING; INTRINSIC ACTIVITY; LIQUID CHROMATOGRAPHY; MASS SPECTROMETRY; NONHUMAN; PRIORITY JOURNAL; PROTEIN DEPHOSPHORYLATION; PROTEIN DETERMINATION; PROTEIN PURIFICATION; PROTEIN QUATERNARY STRUCTURE; SIGNAL TRANSDUCTION; SLOT BLOT HYBRIDIZATION; STEADY STATE; SURFACE PLASMON RESONANCE; CHEMISTRY; ENZYME ASSAY; HUMAN; KINETICS; PROTEIN SUBUNIT; PROTEIN TERTIARY STRUCTURE;

ADENOSINE MONOPHOSPHATE; ALLOSTERIC REGULATION; AMP-ACTIVATED PROTEIN KINASES; ENZYME ACTIVATION; ENZYME ACTIVATORS; ENZYME ASSAYS; HUMANS; ISOENZYMES; KINETICS; PROTEIN STRUCTURE, TERTIARY; PROTEIN SUBUNITS; PYRONES; RECOMBINANT PROTEINS; THIOPHENES;

EID: 84975154466     PISSN: 02646021     EISSN: 14708728     Source Type: Journal    
DOI: 10.1042/BJ20151051     Document Type: Article

References (35)

1. Hardie, D.G., Carling, D. and Carlson, M. (1998) The AMP-activated/SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Ann. Rev. Biochem. 67, 821-855
2. Carling, D., Thornton, C., Woods, A and Sanders, M.J. (2012) AMP-activated protein kinase: new regulation, new roles? Biochem. J. 445, 11-27
3. Oakhill, J.S., Scott, J.W. and Kemp, B.E. (2012) AMPK functions as an adenylate charge-regulated protein kinase. Trends Endocrinol. Metab. 23, 125-132
4. Cheung, P.C., Salt, I.P., Davies, S.P., Hardie, D.G. and Carling, D. (2000) Characterization of AMP-activated protein kinase gamma-subunit isoforms and their role in AMP binding. Biochem. J. 346 (Pt 3), 659-669
5. Stapleton, D., Woollatt, E., Mitchelhill, K.I., Nicholl, J.K., Fernandez, C.S., Michell, B.J., Witters, L.A., Power, D.A., Sutherland, G.R. and Kemp, B.E. (1997) AMP-activated protein kinase isoenzyme family: subunit structure and chromosomal location. FEBS Lett. 409, 452-456
6. Crute, B.E., Seefeld, K., Gamble, J., Kemp, B.E. and Witters, L.A. (1998) Functional domains of the alpha1 catalytic subunit of the AMP-activated protein kinase. J. Biol. Chem. 273, 35347-35354
7. Townley, R. and Shapiro, L. (2007) Crystal structures of the adenylate sensor from fission yeast AMP-activated protein kinase. Science 315, 1726-1729
8. Iseli, T.J., Walter, M., van Denderen, B.J., Katsis, F., Witters, L.A., Kemp, B.E., Michell, B.J. and Stapleton, D. (2005) AMP-activated protein kinase beta subunit tethers alpha and gamma subunits via its C-terminal sequence (186-270). J. Biol. Chem. 280, 13395-13400
9. Mitchelhill, K.I., Michell, B.J., House, C.M., Stapleton, D., Dyck, J., Gamble, J., Ullrich, C., Witters, L.A. and Kemp, B.E. (1997) Posttranslational modifications of the 5′ -AMP-activated protein kinase beta1 subunit. J. Biol. Chem. 272, 24475-24479
10. Kemp, B.E. (2004) Bateman domains and adenosine derivatives form a binding contract. J. Clin. Invest. 113, 182-184
11. Scott, J.W., Hawley, S.A., Green, K.A., Anis, M., Stewart, G., Scullion, G.A., Norman, D.G. and Hardie, D.G. (2004) CBS domains form energy-sensing modules whose binding of adenosine ligands is disrupted by disease mutations. J. Clin. Invest. 113, 274-284
12. Hawley, S.A., Pan, D.A., Mustard, K.J., Ross, L., Bain, J., Edelman, A.M., Frenguelli, B.G. and Hardie, D.G. (2005) Calmodulin-dependent protein kinase kinase-beta is an alternative upstream kinase for AMP-activated protein kinase. Cell Metab. 2, 9-19
13. Sanders, M.J., Grondin, P.O., Hegarty, B.D., Snowden, M.A. and Carling, D. (2007) Investigating the mechanism for AMP activation of the AMP-activated protein kinase cascade. Biochem. J. 403, 139-148
14. Lizcano, J.M., Goransson, O., Toth, R., Deak, M., Morrice, N.A., Boudeau, J., Hawley, S.A., Udd, L., Makela, T.P., Hardie, D.G. and Alessi, D.R. (2004) LKB1 is a master kinase that activates 13 kinases of the AMPK subfamily, including MARK/PAR-1. EMBO J. 23, 833-843
15. Davies, S.P., Helps, N.R., Cohen, P.T. and Hardie, D.G. (1995) 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, 421-425
16. Cool, B., Zinker, B., Chiou, W., Kifle, L., Cao, N., Perham, M., Dickinson, R., Adler, A., Gagne, G., Iyengar, R. et al. (2006) Identification and characterization of a small molecule AMPK activator that treats key components of type 2 diabetes and the metabolic syndrome. Cell Metab. 3, 403-416
17. Goransson, O., McBride, A., Hawley, S.A., Ross, F.A., Shpiro, N., Foretz, M., Viollet, B., Hardie, D.G. and Sakamoto, K. (2007) Mechanism of action of A-769662, a valuable tool for activation of AMP-activated protein kinase. J. Biol. Chem. 282, 32549-32560
18. 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. and Oakhill, J.S. (2014) Small molecule drug A-769662 and AMP synergistically activate naive AMPK independent of upstream kinase signaling. Chem. Biol. 21, 619-627
19. Oakhill, J.S., Chen, Z.P., Scott, J.W., Steel, R., Castelli, L.A., Ling, N., Macaulay, S.L. and Kemp, B.E. (2010) beta-Subunit myristoylation is the gatekeeper for initiating metabolic stress sensing by AMP-activated protein kinase (AMPK). Proc. Natl. Acad. Sci. U.S.A. 107, 19237-19241
20. Xiao, B., Heath, R., Saiu, P., Leiper, F.C., Leone, P., Jing, C., Walker, P.A., Haire, L., Eccleston, J.F., Davis, C.T. et al. (2007) Structural basis for AMP binding to mammalian AMP-activated protein kinase. Nature 449, 496-500
21. Chen, L., Wang, J., Zhang, Y.Y., Yan, S.F., Neumann, D., Schlattner, U., Wang, Z.X. and Wu, J.W. (2012) AMP-activated protein kinase undergoes nucleotide-dependent conformational changes. Nat. Struct. Mol. Biol. 19, 716-718
22. Xiao, B., Sanders, M.J., Underwood, E., Heath, R., Mayer, F.V., Carmena, D., Jing, C., Walker, P.A., Eccleston, J.F., Haire, L.F. et al. (2011) Structure of mammalian AMPK and its regulation by ADP. Nature 472, 230-233
23. Li, X., Wang, L., Zhou, X.E., Ke, J., de Waal, P.W., Gu, X., Tan, M.H., Wang, D., Wu, D., Xu, H.E. and Melcher, K. (2015) Structural basis of AMPK regulation by adenine nucleotides and glycogen. Cell Res. 25, 50-66
24. 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. (2014) Structural basis for AMPK activation: natural and synthetic ligands regulate kinase activity from opposite poles by different molecular mechanisms. Structure 22, 1161-1172
25. 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. (2013) Structural basis of AMPK regulation by small molecule activators. Nat. Commun. 4, 3017
26. Landgraf, R.R., Goswami, D., Rajamohan, F., Harris, M.S., Calabrese, M.F., Hoth, L.R., Magyar, R., Pascal, B.D., Chalmers, M.J., Busby, S.A. et al. (2013) Activation of AMP-activated protein kinase revealed by hydrogen/deuterium exchange mass spectrometry. Structure 21, 1942-1953
27. Wu, J., Puppala, D., Feng, X., Monetti, M., Lapworth, A.L. and Geoghegan, K.F. (2013) Chemoproteomic analysis of intertissue and interspecies isoform diversity of AMP-activated protein kinase (AMPK). J. Biol. Chem. 288, 35904-35912
28. Mounier, R., Theret, M., Lantier, L., Foretz, M and Viollet, B. (2015) Expanding roles for AMPK in skeletal muscle plasticity. Trends Endocrinol. Metab. 26, 275-286
29. Arad, M., Seidman, C.E. and Seidman, J.G. (2007) AMP-activated protein kinase in the heart: role during health and disease. Circ. Res. 100, 474-488
30. Rajamohan, F., Harris, M.S., Frisbie, R.K., Hoth, L.R., Geoghegan, K.F., Valentine, J.J., Reyes, A.R., Landro, J.A., Qiu, X and Kurumbail, R.G. (2010) Escherichia coli expression, purification and characterization of functional full-length recombinant alpha2beta2gamma3 heterotrimeric complex of human AMP-activated protein kinase. Protein Exp. Purif. 73, 189-197
31. Davies, S.P., Carling, D and Hardie, D.G. (1989) Tissue distribution of the AMP-activated protein kinase, and lack of activation by cyclic-AMP-dependent protein kinase, studied using a specific and sensitive peptide assay. Eur. J. Biochem. 186, 123-128
32. Chen, L., Xin, F.J., Wang, J., Hu, J., Zhang, Y.Y., Wan, S., Cao, L.S., Lu, C., Li, P., Yan, S.F. et al. (2013) Conserved regulatory elements in AMPK. Nature 498, E8-E10
33. Salt, I., Celler, J.W., Hawley, S.A., Prescott, A., Woods, A., Carling, D. and Hardie, D.G. (1998) AMP-activated protein kinase: greater AMP dependence, and preferential nuclear localization, of complexes containing the alpha2 isoform. Biochem. J. 334 (Pt 1), 177-187
34. 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. and Kemp, B.E. (2008) Thienopyridone drugs are selective activators of AMP-activated protein kinase beta1-containing complexes. Chem. Biol. 15, 1220-1230
35. Koay, A., Woodcroft, B., Petrie, E.J., Yue, H., Emanuelle, S., Bieri, M., Bailey, M.F., Hargreaves, M., Park, J.T., Park, K.H. et al. (2010) AMPK beta subunits display isoform specific affinities for carbohydrates. FEBS Lett. 584, 3499-3503