The lysosomal v-ATPase-ragulator complex is a common activator for AMPK and mTORC1, acting as a switch between catabolism and anabolism

Cell Metabolism

Volumn 20, Issue 3, 2014, Pages 526-540

  Zhang, Chen Song ^a   Jiang, Bin ^a   Li, Mengqi ^a   Zhu, Mingjiang ^b   Peng, Yongying ^a   Zhang, Ya Lin ^a   Wu, Yu Qing ^a   Li, Terytty Yang ^a   Liang, Yu ^a   Lu, Zailian ^a   Lian, Guili ^a   Liu, Qing ^a   Guo, Huiling ^a   Yin, Zhenyu ^a   Ye, Zhiyun ^a   Han, Jiahuai ^a   Wu, Jia Wei ^c   Yin, Huiyong ^b   Lin, Shu Yong ^a   Lin, Sheng Cai ^a  

^a XIAMEN UNIVERSITY   (China)

^b Shanghai Jiao Tong University Affiliated Sixth People s Hospital   (China)

^c TSINGHUA UNIVERSITY   (China)

Author keywords

[No Author keywords available]

Indexed keywords

ADENOSINE TRIPHOSPHATASE; ADENYLATE KINASE; GUANINE NUCLEOTIDE EXCHANGE FACTOR; MAMMALIAN TARGET OF RAPAMYCIN; AXIN; GLUCOSE; HYDROXYMETHYLGLUTARYL COENZYME A REDUCTASE KINASE; LATE ENDOSOME-LYSOSOME MEMBRANE ADAPTOR P18, MOUSE; MECHANISTIC TARGET OF RAPAMYCIN COMPLEX 1; MULTIPROTEIN COMPLEX; PROTEIN SERINE THREONINE KINASE; PROTON TRANSPORTING ADENOSINE TRIPHOSPHATE SYNTHASE; SIGNAL TRANSDUCING ADAPTOR PROTEIN; STK11 PROTEIN, MOUSE; TARGET OF RAPAMYCIN KINASE; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; PROTEIN KINASE LKB1;

ANIMAL CELL; ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; BIOSYNTHESIS; CATABOLISM; CELL METABOLISM; CELL STRESS; COMPLEX FORMATION; CONTROLLED STUDY; ENERGY TRANSFER; ENZYME ACTIVATION; ENZYME METABOLISM; HUMAN; HUMAN CELL; LYSOSOME; MOUSE; NONHUMAN; PRIORITY JOURNAL; PROTEIN PHOSPHORYLATION; ANIMAL; CELL LINE; ENDOSOME; ENZYMOLOGY; HEK293 CELL LINE; METABOLISM; STARVATION; DISSOCIATION; ENERGY; MOLECULAR DOCKING; SENSOR; STRESS;

ADAPTOR PROTEINS, SIGNAL TRANSDUCING; AMP-ACTIVATED PROTEIN KINASES; ANIMALS; AXIN PROTEIN; CELL LINE; ENDOSOMES; ENZYME ACTIVATION; GLUCOSE; HEK293 CELLS; HUMANS; LYSOSOMES; MICE; MULTIPROTEIN COMPLEXES; PROTEIN-SERINE-THREONINE KINASES; STARVATION; TOR SERINE-THREONINE KINASES; VACUOLAR PROTON-TRANSLOCATING ATPASES;

EID: 84907519033     PISSN: 15504131     EISSN: 19327420     Source Type: Journal    
DOI: 10.1016/j.cmet.2014.06.014     Document Type: Article

References (52)

1. M.M. Assifi, G. Suchankova, S. Constant, M. Prentki, A.K. Saha, and N.B. Ruderman AMP-activated protein kinase and coordination of hepatic fatty acid metabolism of starved/carbohydrate-refed rats Am. J. Physiol. Endocrinol. Metab. 289 2005 E794 E800
2. X.C. Bai, D.Z. Ma, A.L. Liu, X.Y. Shen, Q.J.M. Wang, Y.J. Liu, and Y. Jiang Rheb activates mTOR by antagonizing its endogenous inhibitor, FKBP38 Science 318 2007 977 980
3. L. Bar-Peled, L.D. Schweitzer, R. Zoncu, and D.M. Sabatini Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1 Cell 150 2012 1196 1208
4. L. Bar-Peled, L. Chantranupong, A.D. Cherniack, W.W. Chen, K.A. Ottina, B.C. Grabiner, E.D. Spear, S.L. Carter, M. Meyerson, and D.M. Sabatini A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1 Science 340 2013 1100 1106
5. D. Carling, P.R. Clarke, V.A. Zammit, and D.G. Hardie Purification and characterization of the AMP-activated protein kinase. Copurification of acetyl-CoA carboxylase kinase and 3-hydroxy-3-methylglutaryl-CoA reductase kinase activities Eur. J. Biochem. 186 1989 129 136
6. D. Carling, C. Thornton, A. Woods, and M.J. Sanders AMP-activated protein kinase: new regulation, new roles? Biochem. J. 445 2012 11 27
7. L. Chen, Z.H. Jiao, L.S. Zheng, Y.Y. Zhang, S.T. Xie, Z.X. Wang, and J.W. Wu Structural insight into the autoinhibition mechanism of AMP-activated protein kinase Nature 459 2009 1146 1149
8. S.P. Davies, N.R. Helps, P.T.W. Cohen, and D.G. Hardie 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
9. C.C. Dibble, and B.D. Manning Signal integration by mTORC1 coordinates nutrient input with biosynthetic output Nat. Cell Biol. 15 2013 555 564
10. A. Efeyan, R. Zoncu, S. Chang, I. Gumper, H. Snitkin, R.L. Wolfson, O. Kirak, D.D. Sabatini, and D.M. Sabatini Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival Nature 493 2013 679 683
11. J.P. Gorvel, P. Chavrier, M. Zerial, and J. Gruenberg rab5 controls early endosome fusion in vitro Cell 64 1991 915 925
12. G.J. Gowans, S.A. Hawley, F.A. Ross, and D.G. Hardie 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
13. D.M. Gwinn, D.B. Shackelford, D.F. Egan, M.M. Mihaylova, A. Mery, D.S. Vasquez, B.E. Turk, and R.J. Shaw AMPK phosphorylation of raptor mediates a metabolic checkpoint Mol. Cell 30 2008 214 226
14. D.G. Hardie, F.A. Ross, and S.A. Hawley AMPK: a nutrient and energy sensor that maintains energy homeostasis Nat. Rev. Mol. Cell Biol. 13 2012 251 262
15. S.A. Hawley, M.A. Selbert, E.G. Goldstein, A.M. Edelman, D. Carling, and D.G. Hardie 5′-AMP activates the AMP-activated protein kinase cascade, and Ca2+/calmodulin activates the calmodulin-dependent protein kinase I cascade, via three independent mechanisms J. Biol. Chem. 270 1995 27186 27191
16. S.A. Hawley, J. Boudeau, J.L. Reid, K.J. Mustard, L. Udd, T.P. Mäkelä, D.R. Alessi, and D.G. Hardie 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
17. S.A. Hawley, F.A. Ross, C. Chevtzoff, K.A. Green, A. Evans, S. Fogarty, M.C. Towler, L.J. Brown, O.A. Ogunbayo, A.M. Evans, and D.G. Hardie Use of cells expressing gamma subunit variants to identify diverse mechanisms of AMPK activation Cell Metab. 11 2010 554 565
18. C.C. He, M.C. Bassik, V. Moresi, K. Sun, Y. Wei, Z. Zou, Z. An, J. Loh, J. Fisher, and Q. Sun et al. Exercise-induced BCL2-regulated autophagy is required for muscle glucose homeostasis Nature 481 2012 511 515
19. K. Inoki, Y. Li, T.Q. Zhu, J. Wu, and K.L. Guan TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling Nat. Cell Biol. 4 2002 648 657
20. K. Inoki, H. Ouyang, T. Zhu, C. Lindvall, Y. Wang, X. Zhang, Q. Yang, C. Bennett, Y. Harada, and K. Stankunas et al. TSC2 integrates Wnt and energy signals via a coordinated phosphorylation by AMPK and GSK3 to regulate cell growth Cell 126 2006 955 968
21. A. Kalender, A. Selvaraj, S.Y. Kim, P. Gulati, S. Brûlé, B. Viollet, B.E. Kemp, N. Bardeesy, P. Dennis, and J.J. Schlager et al. Metformin, independent of AMPK, inhibits mTORC1 in a rag GTPase-dependent manner Cell Metab. 11 2010 390 401
22. B.E. Kemp Bateman domains and adenosine derivatives form a binding contract J. Clin. Invest. 113 2004 182 184
23. E. Kim, P. Goraksha-Hicks, L. Li, T.P. Neufeld, and K.L. Guan Regulation of TORC1 by Rag GTPases in nutrient response Nat. Cell Biol. 10 2008 935 945
24. M. Laplante, and D.M. Sabatini mTOR signaling in growth control and disease Cell 149 2012 274 293
25. Y. Li, S.Q. Xu, M.M. Mihaylova, B. Zheng, X.Y. Hou, B.B. Jiang, O. Park, Z.J. Luo, E. Lefai, and J.Y.J. Shyy et al. AMPK phosphorylates and inhibits SREBP activity to attenuate hepatic steatosis and atherosclerosis in diet-induced insulin-resistant mice Cell Metab. 13 2011 376 388
26. L. Ma, Z.B. Chen, H. Erdjument-Bromage, P. Tempst, and P.P. Pandolfi Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis Cell 121 2005 179 193
27. B.D. Manning, A.R. Tee, M.N. Logsdon, J. Blenis, and L.C. Cantley Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/akt pathway Mol. Cell 10 2002 151 162
28. S. Menon, C.C. Dibble, G. Talbott, G. Hoxhaj, A.J. Valvezan, H. Takahashi, L.C. Cantley, and B.D. Manning Spatial control of the TSC complex integrates insulin and nutrient regulation of mTORC1 at the lysosome Cell 156 2014 771 785
29. F. Moore, J. Weekes, and D.G. Hardie Evidence that AMP triggers phosphorylation as well as direct allosteric activation of rat liver AMP-activated protein kinase. A sensitive mechanism to protect the cell against ATP depletion Eur. J. Biochem. 199 1991 691 697
30. J.T. Murray, C. Panaretou, H. Stenmark, M. Miaczynska, and J.M. Backer Role of Rab5 in the recruitment of hVps34/p150 to the early endosome Traffic 3 2002 416 427
31. S. Nada, A. Hondo, A. Kasai, M. Koike, K. Saito, Y. Uchiyama, and M. Okada The novel lipid raft adaptor p18 controls endosome dynamics by anchoring the MEK-ERK pathway to late endosomes EMBO J. 28 2009 477 489
32. J.S. Oakhill, Z.P. Chen, J.W. Scott, R. Steel, L.A. Castelli, N. Ling, S.L. Macaulay, and B.E. Kemp β-Subunit myristoylation is the gatekeeper for initiating metabolic stress sensing by AMP-activated protein kinase (AMPK) Proc. Natl. Acad. Sci. USA 107 2010 19237 19241
33. J.S. Oakhill, R. Steel, Z.P. Chen, J.W. Scott, N. Ling, S. Tam, and B.E. Kemp AMPK is a direct adenylate charge-regulated protein kinase Science 332 2011 1433 1435
34. N. Panchaud, M.P. Péli-Gulli, and C. De Virgilio Amino acid deprivation inhibits TORC1 through a GTPase-activating protein complex for the Rag family GTPase Gtr1 Sci. Signal. 6 2013 ra42
35. C.J. Potter, L.G. Pedraza, and T. Xu Akt regulates growth by directly phosphorylating Tsc2 Nat. Cell Biol. 4 2002 658 665
36. J. Rink, E. Ghigo, Y. Kalaidzidis, and M. Zerial Rab conversion as a mechanism of progression from early to late endosomes Cell 122 2005 735 749
37. P.P. Roux, B.A. Ballif, R. Anjum, S.P. Gygi, and J. Blenis Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase Proc. Natl. Acad. Sci. USA 101 2004 13489 13494
38. Y.N. Rui, Z. Xu, S.Y. Lin, Q.X. Li, H.L. Rui, W. Luo, H.M. Zhou, P.Y. Cheung, Z.G. Wu, and Z.Y. Ye et al. Axin stimulates p53 functions by activation of HIPK2 kinase through multimeric complex formation EMBO J. 23 2004 4583 4594
39. K. Sakamoto, A. McCarthy, D. Smith, K.A. Green, D. Grahame Hardie, A. Ashworth, and D.R. Alessi Deficiency of LKB1 in skeletal muscle prevents AMPK activation and glucose uptake during contraction EMBO J. 24 2005 1810 1820
40. Y. Sancak, T.R. Peterson, Y.D. Shaul, R.A. Lindquist, C.C. Thoreen, L. Bar-Peled, and D.M. Sabatini The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1 Science 320 2008 1496 1501
41. Y. Sancak, L. Bar-Peled, R. Zoncu, A.L. Markhard, S. Nada, and D.M. Sabatini Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids Cell 141 2010 290 303
42. C. Settembre, A. Fraldi, D.L. Medina, and A. Ballabio Signals from the lysosome: a control centre for cellular clearance and energy metabolism Nat. Rev. Mol. Cell Biol. 14 2013 283 296
43. D.B. Shackelford, and R.J. Shaw The LKB1-AMPK pathway: metabolism and growth control in tumour suppression Nat. Rev. Cancer 9 2009 563 575
44. R.J. Shaw, M. Kosmatka, N. Bardeesy, R.L. Hurley, L.A. Witters, R.A. DePinho, and L.C. Cantley The tumor suppressor LKB1 kinase directly activates AMP-activated kinase and regulates apoptosis in response to energy stress Proc. Natl. Acad. Sci. USA 101 2004 3329 3335
45. R.J. Shaw, K.A. Lamia, D. Vasquez, S.H. Koo, N. Bardeesy, R.A. Depinho, M. Montminy, and L.C. Cantley The kinase LKB1 mediates glucose homeostasis in liver and therapeutic effects of metformin Science 310 2005 1642 1646
46. G.R. Steinberg, and B.E. Kemp AMPK in Health and Disease Physiol. Rev. 89 2009 1025 1078
47. B.E. Steinberg, K.K. Huynh, A. Brodovitch, S. Jabs, T. Stauber, T.J. Jentsch, and S. Grinstein A cation counterflux supports lysosomal acidification J. Cell Biol. 189 2010 1171 1186
48. H. Stenmark, R.G. Parton, O. Steele-Mortimer, A. Lütcke, J. Gruenberg, and M. Zerial Inhibition of rab5 GTPase activity stimulates membrane fusion in endocytosis EMBO J. 13 1994 1287 1296
49. A. Woods, S.R. Johnstone, K. Dickerson, F.C. Leiper, L.G.D. Fryer, D. Neumann, U. Schlattner, T. Wallimann, M. Carlson, and D. Carling LKB1 is the upstream kinase in the AMP-activated protein kinase cascade Curr. Biol. 13 2003 2004 2008
50. B. Xiao, R. Heath, P. Saiu, F.C. Leiper, P. Leone, C. Jing, P.A. Walker, L. Haire, J.F. Eccleston, and C.T. Davis et al. Structural basis for AMP binding to mammalian AMP-activated protein kinase Nature 449 2007 496 500
51. Y.L. Zhang, H.L. Guo, C.S. Zhang, S.Y. Lin, Z.Y. Yin, Y.Y. Peng, H. Luo, Y.Z. Shi, G.L. Lian, and C.X. Zhang 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
52. R. Zoncu, L. Bar-Peled, A. Efeyan, S. Wang, Y. Sancak, and D.M. Sabatini mTORC1 senses lysosomal amino acids through an inside-out mechanism that requires the vacuolar H(+)-ATPase Science 334 2011 678 683