Metformin activates AMP-activated protein kinase by promoting formation of the αβγheterotrimeric complex

Journal of Biological Chemistry

Volumn 290, Issue 6, 2015, Pages 3393-3802

  Meng, Shumei ^a   Cao, Jia ^a   He, Qiyi ^a   Xiong, Lishou ^a   Chang, Evan ^a   Radovick, Sally ^b   Wondisford, Fredric E ^a   He, Ling ^a  

^a Departments of Pediatrics Medicine and Physiology   (United States)

^b JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

CHEMICAL ACTIVATION; PHOSPHORYLATION; PROTEINS;

AMP-ACTIVATED PROTEIN KINASE; DEPHOSPHORYLATIONS; METFORMINS; PROTEIN PHOSPHATASE;

ENZYME ACTIVITY;

HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE ALPHA; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE ALPHA BETA GAMMA HETEROTRIMERIC COMPLEX; METFORMIN; PHOSPHOPROTEIN PHOSPHATASE; PROTEIN KINASE LKB1; PROTEIN PHOSPHATASE 2C; THREONINE; UNCLASSIFIED DRUG; ANTIDIABETIC AGENT; PHOSPHOPROTEIN PHOSPHATASE 2; PROTEIN BINDING; PROTEIN SERINE THREONINE KINASE; PROTEIN SUBUNIT; STK11 PROTEIN, MOUSE;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL TISSUE; ARTICLE; CATALYSIS; CONCENTRATION RESPONSE; CONTROLLED STUDY; DRUG MECHANISM; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; MOUSE; NONHUMAN; PROTEIN DEPHOSPHORYLATION; PROTEIN PROTEIN INTERACTION; ANIMAL; CELL CULTURE; DRUG EFFECTS; LIVER CELL; METABOLISM; PHOSPHORYLATION; PROTEIN MULTIMERIZATION; PROTEIN SUBUNIT; TUMOR CELL LINE;

AMP-ACTIVATED PROTEIN KINASES; ANIMALS; CELL LINE, TUMOR; CELLS, CULTURED; HEPATOCYTES; HYPOGLYCEMIC AGENTS; METFORMIN; MICE; PHOSPHORYLATION; PROTEIN BINDING; PROTEIN MULTIMERIZATION; PROTEIN PHOSPHATASE 2; PROTEIN SUBUNITS; PROTEIN-SERINE-THREONINE KINASES;

EID: 84922359822     PISSN: 00219258     EISSN: 1083351X     Source Type: Journal    
DOI: 10.1074/jbc.M114.604421     Document Type: Article

References (38)

1. Witters, L. A. (2001) The blooming of the French lilac. J. Clin. Invest. 108, 1105-1107.
2. Hundal, R. S., Krssak, M., Dufour, S., Laurent, D., Lebon, V., Chandramouli, V., Inzucchi, S. E., Schumann, W. C., Petersen, K. F., Landau, B. R., and Shulman, G. I. (2000) Mechanism by which metformin reduces glucose production in type 2 diabetes. Diabetes 49, 2063-2069.
3. Takashima, M., Ogawa, W., Hayashi, K., Inoue, H., Kinoshita, S., Okamoto, Y., Sakaue, H., Wataoka, Y., Emi, A., Senga, Y., Matsuki, Y., Watanabe, E., Hiramatsu, R., and Kasuga, M. (2010) Role of KLF15 in regulation of hepatic gluconeogenesis and metformin action. Diabetes 59, 1608-1615.
4. Zhou, G., Myers, R., Li, Y., Chen, Y., Shen, X., Fenyk-Melody, J., Wu, M., Ventre, J., Doebber, T., Fujii, N., Musi, N., Hirshman, M. F., Goodyear, L. J., and Moller, D. E. (2001) Role of AMP-activated protein kinase in mechanism of metformin action. J. Clin. Invest. 108, 1167-1174.
5. Owen M. R., Doran E., and Halestrap A. P. (2000) Evidence that metformin exerts its anti-diabetic effects through inhibition of complex 1 of the mitochondrial respiratory chain. Bio chem. J. 348, 607-614.
6. El-Mir, M. Y., Nogueira, V., Fontaine, E., Avéret, N., Rigoulet, M., and Leverve, X. (2000) Dimethylbiguanide inhibits cell respiration via an indirect effect targeted on the respiratory chain complex I. J. Biol. Chem. 275, 223-228.
7. Cao, J., Meng, S., Chang, E., Beckwith-Fickas, K., Xiong, L., Cole, R. N., Radovick, S., Wondisford, F. E., and He, L. (2014) Low concentrations of metformin suppress glucose production in hepatocytes through AMPK. J. Biol. Chem. 289, 20435-20446.
8. Ha, J., Daniel, S., Broyles, S. S., Kim, K. H. (1994) Critical phosphorylation sites for acetyl-CoA carboxylase activity. J. Biol. Chem. 269, 22162-22168.
9. Dyck, J. R. B., Kudo, N., Barr, A. J., Davies, S. P., Hardie, D. G., and Lopaschuk, G. D. (1999) Phosphorylation control of cardiac acetyl-CoA carboxylase by cAMP-dependent protein kinase and 5-AMP activated protein kinase. Eur. J. Bio chem. 262, 184-190.
10. Hardie, D. G., Ross, F. A., and Hawley, S. A. (2012) AMPK: A nutrient and energy sensor that maintains energy homeostasis. Nat. Rev. Mol. Cell Biol. 13, 251-262.
11. Lizcano, J. M., Göransson, O., Toth, R., Deak, M., Morrice, N. A., Boudeau, J., Hawley, S. A., Udd, L., Mäkelä, T. P., Hardie, D. G., 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.
12. Woods, A., Johnstone, S. R., Dickerson, K., Leiper, F. C., Fryer, L. G., Neumann, D., Schlattner, U., Wallimann, T., Carlson, M., Carling, D. (2003) LKB1 is the upstream kinase in the AMP-activated protein kinase cascade. Curr. Biol. 13, 2004-2008.
13. Djouder, N., Tuerk, R. D., Suter, M., Salvioni, P., Thali, R. F., Scholz, R., Vaahtomeri, K., Auchli, Y., Rechsteiner, H., Brunisholz, R. A., Viollet, B., Mäkelä, T. P., Wallimann, T., Neumann, D., and Krek, W. (2010) PKA phosphorylates and inactivates AMP Kalpha to promote efficient lipolysis. EMBO J. 29, 469-481.
14. Hurley, R. L., Barré, L. K., Wood, S. D., Anderson, K. A., Kemp, B. E., Means, A. R., and Witters, L. A. (2006) Regulation of AMP-activated protein kinase by multisite phosphorylation in response to agents that elevate cellular cAMP. J. Biol. Chem. 281, 36662-36672.
15. Ning, J., Xi, G., and Clemmons, D. R. (2011) Suppression of AMPK activation via S485 phosphorylation by IGF-I during hyperglycemia is mediated by AKT activation in vascular smooth muscle cells. Endocrinology 152, 3143-3154.
16. Xiao, B., Heath, R., Saiu, P., Leiper, F. C., Leone, P., Jing, C., Walker, P. A., Haire, L., Eccleston, J. F., Davis, C. T., Martin, S. R., Carling, D., and Gamblin, S. J. (2007) Structural basis for AMP binding to mammalian AMPactivated protein kinase. Nature 449, 496-500.
17. Davies, S. P., Helps, N. R., Cohen, P. T., 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- and native bovine protein phosphatase-2AC. FEBS Lett. 377, 421-425.
18. Shaw, R. J., Lamia, K. A., Vasquez, D., Koo, S. H., Bardeesy, N., Depinho, R. A., Montminy, M., and Cantley, L. C. (2005) The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin. Science 310, 1642-1646.
19. He, L., Sabet, A., Djedjos, S., Miller, R., Sun, X., Hussain, M. A., Radovick, S., Wondisford, F. E. (2009) Metformin and insulin suppress hepatic gluconeogenesis through phosphorylation of CREB binding protein. Cell 137, 635-646.
20. Martin-Montalvo, A., Mercken, E. M., Mitchell, S. J., Palacios, H. H., Mote, P. L., Scheibye-Knudsen, M., Gomes, A. P., Ward, T. M., Minor, R. K., Blouin, M. J., Schwab, M., Pollak, M., Zhang, Y., Yu, Y., Becker, K. G., Bohr, V. A., Ingram, D. K., Sinclair, D. A., Wolf, N. S., Spindler, S. R., Bernier, M., and de Cabo, R. (2013) Metformin improves healthspan and lifespan in mice. Nat. Commun. 4, 1-7.
21. Heishi, M., Hayashi, K., Ichihara, J., Ishikawa, H., Kawamura, T., Kanaoka, M., Taiji, M., Kimura, T. (2008) Comparison of gene expression changes induced by biguanides in db/db mice liver. J. Toxicol. Sci. 33, 339-347.
22. Aatsinki, S. M., Buler, M., Salomäki, H., Koulu, M., Pavek, P., Hakkola, J. (2014) Metformin induces PGC-1- expression and selectively affects hepatic PGC-1- functions. Br. J. Pharmacol. 171, 2351-2363.
23. Kim, Y. D., Li, T., Ahn, S. W., Kim, D. K., Lee, J. M., Hwang, S. L., Kim, Y. H., Lee, C. H., Lee, I. K., Chiang, J. Y., Choi, H. S. (2012) Orphan nuclear receptor small heterodimer partner negatively regulates growth hormone- mediated induction of hepatic gluconeogenesis through inhibition of signal transducer and activator of transcription 5 (STAT5) transactivation. J. Biol. Chem. 287, 37098-37108.
24. Cheng, J. T., Huang, C. C., Liu, I. M., Tzeng, T. F., Chang, C. J. (2006) Novel mechanism for plasma glucose-lowering action of metformin in streptozotocin- induced diabetic rats. Diabetes 55, 819-825.
25. He, L., Meng, S., Germain-Lee, E. L., Radovick, S., Wondisford, F. E. (2014) Potential biomarker of metformin action. J. Endocrinol. 221, 363-369.
26. Koo, S. H., Flechner, L., Qi, L., Zhang, X., Screaton, R. A., Jeffries, S., Hedrick, S., Xu, W., Boussouar, F., Brindle, P., Takemori, H., and Montminy, M. (2005) The CREB coactivator TORC2 is a key regulator of fasting glucose metabolism. Nature 437, 1109-1111.
27. He, L., Naik, K., Meng, S., Cao, J., Sidhaye, A. R., Ma, A., Radovick, S., and Wondisford, F. E. (2012) Transcriptional co-activator p300 maintains basal hepatic gluconeogenesis. J. Biol. Chem. 287, 32069-32077.
28. Wondisford, A. R., Xiong, L., Chang, E., Meng, S., Meyers, D. J., Li, M., Cole, P. A., He, L. (2014) Control of Foxo1 gene expression by co-activator p300. J. Biol. Chem. 289, 4326-4333.
29. He, L., Cao, J., Meng, S., Ma, A., Radovick, S., and Wondisford, F. E. (2013) Activation of basal gluconeogenesis by co-activator p300 maintains hepatic glycogen storage. Mol. Endo. 27, 1322-1332.
30. Davies, S. P., Hawley, S. A., Woods, A., Carling, D., Haystead, T. A. J., and Hardie, D. G. (1994) Purification of the AMP-activated protein kinase on ATP-Sepharose and analysis of its subunit structure. Eur. J. Biochem. 223, 351-357.
31. Stapleton, D., Mitchelhill, K., Gao, G., Widmer, J., Michell, B., Teh, T., House, C. M., Fernandez, C. S., Cox, T., Witters, L. A., and Kemp, B. E. (1996) Mammalian AMP-activated protein kinase subfamily. J. Biol. Chem. 271, 611-614.
32. Hawley, S. A., Gadalla, A. E., Olsen, G. S., Hardie, D. G. (2002) The antidiabetic drug metformin activates the AMP-activated protein kinase cascade via an adenine nucleotide-independent mechanism. Diabetes 51, 2420-2425.
33. Merrill, G. F., Kurth, E. J., Hardie, D. G., and Winder, W. W. (1997) AICA riboside increases AMP-activated protein kinase, fatty acid oxidation, and glucose uptake in rat muscle. Am. J. Physiol. 273, E1107-E1112.
34. 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.
35. Hardie, D. G., Carling, D., and Gamblin, S. J. (2011) AMP-activated protein kinase: Also regulated by ADP? Trends Bio chem. Sci. 36, 470-477.
36. Mitchelhill, K. I., Stapleton, D., Gao, G., House, C., Michell, B., Katsis, F., Witters, L. A., and Kemp, B. E. (1994) Mammalian AMP-activated protein kinase shares structural and functional homology with the catalytic domain of yeast Snf1 protein kinase. J. Biol. Chem. 269, 2361-2364.
37. Stapleton, D., Gao, G., Michell, B. J., Widmer, J., Mitchelhill, K. I., The, T., House, C. M., Witters, L. A., and Kemp, B. E. (1994) Mammalian 5-AMPactivated protein kinase non-catalytic subunits are homologs of proteins that interact with yeast Snf1 protein kinase. J. Biol. Chem. 269, 29343-29346.
38. Kalender, A., Selvaraj, A., Kim, S. Y., Gulati, P., Brûlé, S., Viollet, B., Kemp, B. E., Bardeesy, N., Dennis, P., Schlager, J. J., Marette, A., Kozma, S. C., and Thomas, G. (2010) Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner. Cell Metab. 11, 390-401.