In scarcity and abundance: Metabolic signals regulating cell growth

Physiology

Volumn 28, Issue 5, 2013, Pages 298-309

  Saad, Shady ^a,b   Peter, Matthias ^a,c   Dechant, Reinhard ^a,c  

^a ETH ZURICH   (Switzerland)

^b Life Science Zurich   (Switzerland)

^c Competence Center for Systems Physiology and Metabolic Diseases ^*  (Switzerland)

Author keywords

[No Author keywords available]

Indexed keywords

ADAPTATION; ANIMAL; CELL ENLARGEMENT; CELL PROLIFERATION; CELL SURVIVAL; ENERGY METABOLISM; HUMAN; MOLECULAR EVOLUTION; REVIEW; SIGNAL TRANSDUCTION;

ADAPTATION, PHYSIOLOGICAL; ANIMALS; CELL ENLARGEMENT; CELL PROLIFERATION; CELL SURVIVAL; ENERGY METABOLISM; EVOLUTION, MOLECULAR; HUMANS; SIGNAL TRANSDUCTION;

EID: 84883431234     PISSN: 15489213     EISSN: 15489221     Source Type: Journal    
DOI: 10.1152/physiol.00005.2013     Document Type: Review

References (158)

1. Ahuatzi D, Herrero P, de la Cera T, Moreno F. The glucoseregulated nuclear localization of hexokinase 2 in Saccharomyces cerevisiae is Mig1-dependent. J Biol Chem 279: 14440-14446, 2004.
2. Alms GR, Sanz P, Carlson M, Haystead TA. Reg1p targets protein phosphatase 1 to dephosphorylate hexokinase II in Saccharomyces cerevisiae: characterizing the effects of a phosphatase subunit on the yeast proteome. EMBO J 18: 4157-4168, 1999.
3. Anastasiou D, Yu Y, Israelsen WJ, Jiang JK, Boxer MB, Hong BS, Tempel W, Dimov S, Shen M, Jha A, Yang H, Mattaini KR, Metallo CM, Fiske BP, Courtney KD, Malstrom S, Khan TM, Kung C, Skoumbourdis AP, Veith H, Southall N, Walsh MJ, Brimacombe KR, Leister W, Lunt SY, Johnson ZR, Yen KE, Kunii K, Davidson SM, Christofk HR, Austin CP, Inglese J, Harris MH, Asara JM, Stephanopoulos G, Salituro FG, Jin S, Dang L, Auld DS, Park HW, Cantley LC, Thomas CJ, Vander Heiden MG. Pyruvate kinase M2 activators promote tetramer formation and suppress tumorigenesis. Nat Chem Biol 8: 839-847, 2012.
4. Aronova S, Wedaman K, Aronov PA, Fontes K, Ramos K, Hammock BD, Powers T. Regulation of ceramide biosynthesis by TOR complex 2. Cell Metab 7: 148-158, 2008.
5. Balcazar N, Sathyamurthy A, Elghazi L, Gould A, Weiss A, Shiojima I, Walsh K, Bernal-Mizrachi E. mTORC1 activation regulates beta-cell mass and proliferation by modulation of cyclin D2 synthesis and stability. J Biol Chem 284: 7832-7842, 2009.
6. Bar-Peled L, Schweitzer LD, Zoncu R, Sabatini DM. Ragulator is a GEF for the rag GTPases that signal amino acid levels to mTORC1. Cell 150: 1196-1208, 2012.
7. Bell GI, Polonsky KS. Diabetes mellitus and genetically programmed defects in beta-cell function. Nature 414: 788-791, 2001.
8. Bensinger SJ, Christofk HR. New aspects of the Warburg effect in cancer cell biology. Semin Cell Dev Biol 23: 352-361, 2012.
9. Berchtold D, Piccolis M, Chiaruttini N, Riezman I, Riezman H, Roux A, Walther TC, Loewith R. Plasma membrane stress induces relocalization of Slm proteins and activation of TORC2 to promote sphingolipid synthesis. Nat Cell Biol 14: 542-547, 2012.
10. Bernstein KA, Bleichert F, Bean JM, Cross FR, Baserga SJ. Ribosome biogenesis is sensed at the Start cell cycle checkpoint. Mol Biol Cell 18: 953-964, 2007.
11. + exchanger (NHE1 isoform) in response to growth factors. J Biol Chem 272: 271-279, 1997.
12. Binda M, Peli-Gulli MP, Bonfils G, Panchaud N, Urban J, Sturgill TW, Loewith R, De Virgilio C. The Vam6 GEF controls TORC1 by activating the EGO complex. Mol Cell 35: 563-573, 2009.
13. Blandino-Rosano M, Chen AY, Scheys JO, Alejandro EU, Gould AP, Taranukha T, Elghazi L, Cras-Meneur C, Bernal-Mizrachi E. mTORC1 signaling and regulation of pancreatic beta-cell mass. Cell Cycle 11: 1892-1902, 2012.
14. Bodenmiller B, Wanka S, Kraft C, Urban J, Campbell D, Pedrioli PG, Gerrits B, Picotti P, Lam H, Vitek O, Brusniak MY, Roschitzki B, Zhang C, Shokat KM, Schlapbach R, Colman-Lerner A, Nolan GP, Nesvizhskii AI, Peter M, Loewith R, von Mering C, Aebersold R. Phosphoproteomic analysis reveals interconnected system-wide responses to perturbations of kinases and phosphatases in yeast. Sci Signal 3: rs4, 2010.
15. Bonfils G, Jaquenoud M, Bontron S, Ostrowicz C, Ungermann C, De Virgilio C. Leucyl-tRNA synthetase controls TORC1 via the EGO complex. Mol Cell 46: 105-110, 2012.
16. Broach JR. Nutritional control of growth and development in yeast. Genetics 192: 73-105, 2012.
17. Cai L, Sutter BM, Li B, Tu BP. Acetyl-CoA induces cell growth and proliferation by promoting the acetylation of histones at growth genes. Mol Cell 42: 426-437, 2011.
18. Cai L, Tu BP. Driving the cell cycle through metabolism. Ann Rev Cell Dev Biol 28: 59-87, 2012.
19. Carmen GY, Victor SM. Signalling mechanisms regulating lipolysis. Cell Signal 18: 401-408, 2006.
20. Cherkasova VA, Hinnebusch AG. Translational control by TOR and TAP42 through dephosphorylation of eIF2alpha kinase GCN2. Genes Dev 17: 859-872, 2003.
21. + exchanger NHE1 by post-translational regulation that is important for cervical cancer cell invasiveness. J Cell Physiol 214: 810-819, 2008.
22. Christofk HR, Vander Heiden MG, Harris MH, Ramanathan A, Gerszten RE, Wei R, Fleming MD, Schreiber SL, Cantley LC. The M2 splice isoform of pyruvate kinase is important for cancer metabolism and tumour growth. Nature 452: 230-233, 2008.
23. Christofk HR, Vander Heiden MG, Wu N, Asara JM, Cantley LC. Pyruvate kinase M2 is a phosphotyrosine-binding protein. Nature 452: 181-186, 2008.
24. + exchanger in podocytes through a mechanism that involves Janus kinase and calmodulin. Biochim Biophys Acta 1793: 1174-1181, 2009.
25. Colell A, Green DR, Ricci JE. Novel roles for GAPDH in cell death and carcinogenesis. Cell Death Diff 16: 1573-1581, 2009.
26. Conlon I, Raff M. Differences in the way a mammalian cell and yeast cells coordinate cell growth and cell-cycle progression. J Biol 2: 7, 2003.
27. Conlon IJ, Dunn GA, Mudge AW, Raff MC. Extracellular control of cell size. Nat Cell Biol 3: 918-921, 2001.
28. Costes S, Longuet C, Broca C, Faruque O, Hani EH, Bataille D, Dalle S. Cooperative effects between protein kinase A and p44/p42 mitogen-activated protein kinase to promote cAMP-responsive element binding protein activation after beta cell stimulation by glucose and its alteration due to glucotoxicity. Ann NY Acad Sci 1030: 230-242, 2004.
29. Crespo JL, Powers T, Fowler B, Hall MN. The TOR-controlled transcription activators GLN3, RTG1, and RTG3 are regulated in response to intracellular levels of glutamine. Proc Natl Acad Sci USA 99: 6784-6789, 2002.
30. De Virgilio C, Loewith R. Cell growth control: little eukaryotes make big contributions. Oncogene 25: 6392-6415, 2006.
31. DeBerardinis RJ, Lum JJ, Hatzivassiliou G, Thompson CB. The biology of cancer: metabolic reprogramming fuels cell growth and proliferation. Cell Metab 7: 11-20, 2008.
32. Dechant R, Binda M, Lee SS, Pelet S, Winderickx J, Peter M. Cytosolic pH is a second messenger for glucose and regulates the PKA pathway through V-ATPase. EMBO J 29: 2515-2526, 2010.
33. Dechant R, Peter M. The N-terminal domain of the V-ATPase subunit 'a' is regulated by pH in vitro and in vivo. Channels (Austin) 5: 4-8, 2011.
34. Dechant R, Peter M. Nutrient signals driving cell growth. Curr Opin Cell Biol 20: 678-687, 2008.
35. Dennis PB, Jaeschke A, Saitoh M, Fowler B, Kozma SC, Thomas G. Mammalian TOR: a homeostatic ATP sensor. Sci Signal 294: 1102, 2001.
36. Di Talia S, Wang H, Skotheim JM, Rosebrock AP, Futcher B, Cross FR. Daughter-specific transcription factors regulate cell size control in budding yeast. PLoS Biol 7: e1000221, 2009.
37. Diaz-Ruiz R, Rigoulet M, Devin A. The Warburg and Crabtree effects: on the origin of cancer cell energy metabolism and of yeast glucose repression. Biochim Biophys Acta 1807: 568-576, 2011.
38. Dilova I, Aronova S, Chen JCY, Powers T. Tor signaling and nutrient-based signals converge on Mks1p phosphorylation to regulate expression of Rtg1. Rtg3p-dependent target genes. J Biol Chem 279: 46527-46535, 2004.
39. Dolznig H, Grebien F, Sauer T, Beug H, Mullner EW. Evidence for a size-sensing mechanism in animal cells. Nat Cell Biol 6: 899-905, 2004.
40. Dombrauckas JD, Santarsiero BD, Mesecar AD. Structural basis for tumor pyruvate kinase M2 allosteric regulation and catalysis. Biochemistry 44: 9417-9429, 2005.
41. Dong J, Qiu H, Garcia-Barrio M, Anderson J, Hinnebusch AG. Uncharged tRNA activates GCN2 by displacing the protein kinase moiety from a bipartite tRNA-binding domain. Mol Cell 6: 269-279, 2000.
42. Dor Y, Brown J, Martinez OI, Melton DA. Adult pancreatic beta-cells are formed by self-duplication rather than stem-cell differentiation. Nature 429: 41-46, 2004.
43. Dubouloz F, Deloche O, Wanke V, Cameroni E, De Virgilio C. The TOR and EGO protein complexes orchestrate microautophagy in yeast. Mol Cell 19: 15-26, 2005.
44. Efeyan A, Zoncu R, Chang S, Gumper I, Snitkin H, Wolfson RL, Kirak O, Sabatini DD, Sabatini DM. Regulation of mTORC1 by the Rag GTPases is necessary for neonatal autophagy and survival. Nature 493: 679-683, 2013.
45. Fernandez-Garcia P, Peláez R, Herrero P, Moreno F. Phosphorylation of yeast hexokinase 2 regulates its nucleocytoplasmic shuttling. J Biol Chem 287: 42151-42164, 2012.
46. Ficarro SB, McCleland ML, Stukenberg PT, Burke DJ, Ross MM, Shabanowitz J, Hunt DF, White FM. Phosphoproteome analysis by mass spectrometry and its application to Saccharomyces cerevisiae. Nat Biotech 20: 301-305, 2002.
47. Fingar DC, Blenis J. Target of rapamycin (TOR): an integrator of nutrient and growth factor signals and coordinator of cell growth and cell cycle progression. Oncogene 23: 3151-3171, 2004.
48. Forgac M. Vacuolar ATPases: rotary proton pumps in physiology and pathophysiology. Nat Rev Mol Cell Biol 8: 917-929, 2007.
49. Ganapathy V, Thangaraju M, Prasad PD. Nutrient transporters in cancer: relevance to Warburg hypothesis and beyond. Pharmacol Therap 121: 29-40, 2009.
50. Gancedo JM, Serrano R. Energy yielding metabolism. In: The Yeasts (2nd ed.), edited by Rose AH, Harrison JS. New York: Academic, 1988, p. 205.
51. Gao X, Wang H, Yang JJ, Liu X, Liu ZR. Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase. Mol Cell 45: 598-609, 2012.
52. Gao X, Wang H, Yang JJ, Liu X, Liu ZR. Pyruvate kinase M2 regulates gene transcription by acting as a protein kinase. Mol Cell 45: 598-609, 2012.
53. Ghillebert R, Swinnen E, Wen J, Vandesteene L, Ramon M, Norga K, Rolland F, Winderickx J. The AMPK/SNF1/SnRK1 fuel gauge and energy regulator: structure, function and regulation. FEBS J 278: 3978-3990, 2011.
54. Giots F, Donaton MCV, Thevelein JM. Inorganic phosphate is sensed by specific phosphate carriers and acts in concert with glucose as a nutrient signal for activation of the protein kinase A pathway in the yeast Saccharomyces cerevisiae. Mol Microbiol 47: 1163-1181, 2003.
55. Gojon A, Krouk G, Perrine-Walker F, Laugier E. Nitrate transceptor(s) in plants. J Exp Bot 62: 2299-2308, 2011.
56. Gong R, Li L, Liu Y, Wang P, Yang H, Wang L, Cheng J, Guan KL, Xu Y. Crystal structure of the Gtr1p-Gtr2p complex reveals new insights into the amino acid-induced TORC1 activation. Genes Dev 25: 1668-1673, 2011.
57. 2+CaM signaling to hVps34. Cell Metab 7: 456-465, 2008.
58. Gunawardana SC, Rocheleau JV, Head WS, Piston DW. Nutrient-stimulated insulin secretion in mouse islets is critically dependent on intracellular pH. BMC Endocr Disord 4: 1, 2004.
59. Han JM, Jeong SJ, Park MC, Kim G, Kwon NH, Kim HK, Ha SH, Ryu SH, Kim S. Leucyl-tRNA synthetase is an intracellular leucine sensor for the mTORC1-signaling pathway. Cell 149: 410-424, 2012.
60. Hara K, Yonezawa K, Weng QP, Kozlowski MT, Belham C, Avruch J. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J Biol Chem 273: 14484-14494, 1998.
61. Harada N, Yasunaga R, Higashimura Y, Yamaji R, Fujimoto K, Moss J, Inui H, Nakano Y. Glyceraldehyde-3-phosphate dehydrogenase enhances transcriptional activity of androgen receptor in prostate cancer cells. J Biol Chem 282: 22651-22661, 2007.
62. Hardie DG. AMP-activated/SNF1 protein kinases: conserved guardians of cellular energy. Nat Rev Mol Cell Biol 8: 774-785, 2007.
63. Hardie DG, Carling D, Carlson M. The AMP-activated/ SNF1 protein kinase subfamily: metabolic sensors of the eukaryotic cell? Annu Rev Biochem 67: 821-855, 1998.
64. Hatakeyama H, Kishimoto T, Nemoto T, Kasai H, Takahashi N. Rapid glucose sensing by protein kinase A for insulin exocytosis in mouse pancreatic islets. J Physiol 570: 271-282, 2006.
65. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 18: 1926-1945, 2004.
66. Heitman J, Movva NR, Hall MN. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253: 905-909, 1991.
67. Herrero P, Galíndez J, Ruiz N, Martínez-Campa C, Moreno F. Transcriptional regulation of the Saccharomyces cerevisiae HXK1, HXK2 and GLK1 genes. Yeast 11: 137-144, 1995.
68. Hosiner D, Lempiäinen H, Reiter W, Urban J, Loewith R, Ammerer G, Schweyen R, Shore D, Schüller C. Arsenic toxicity to Saccharomyces cerevisiae is a consequence of inhibition of the TORC1 kinase combined with a chronic stress response. Mol Biol Cell 20: 1048-1057, 2009.
69. Huang Q, Lan F, Zheng Z, Xie F, Han J, Dong L, Xie Y, Zheng F. Akt2 kinase suppresses glyceraldehyde-3-phosphate dehydrogenase (GAPDH)-mediated apoptosis in ovarian cancer cells via phosphorylating GAPDH at threonine 237 and decreasing its nuclear translocation. J Biol Chem 286: 42211-42220, 2011.
70. Huber A, Bodenmiller B, Uotila A, Stahl M, Wanka S, Gerrits B, Aebersold R, Loewith R. Characterization of the rapamycin-sensitive phosphoproteome reveals that Sch9 is a central coordinator of protein synthesis. Genes Dev 23: 1929-1943, 2009.
71. Hyde R, Cwiklinski EL, MacAulay K, Taylor PM, Hundal HS. Distinct sensor pathways in the hierarchical control of SNAT2, a putative amino acid transceptor, by amino acid availability. J Biol Chem 282: 19788-19798, 2007.
72. Inoki K, Ouyang H, Li Y, Guan KL. Signaling by target of rapamycin proteins in cell growth control. Microbiol Mol Biol Rev 69: 79-100, 2005.
73. + exchanger-1 (NHE1) is required for growth factorinduced mammary branching morphogenesis. Dev Biol 365: 71-81, 2012.
74. Jiang G, Zhang BB. Glucagon and regulation of glucose metabolism. Am J Physiol Endocrinol Metab 284: E671-E678, 2003.
75. Jorgensen P, Nishikawa JL, Breitkreutz BJ, Tyers M. Systematic identification of pathways that couple cell growth and division in yeast. Science 297: 395-400, 2002.
76. Jorgensen P, Tyers M. How cells coordinate growth and division. Curr Biol 14: 1014-1027, 2004.
77. + exchange, an effect not dependent on protein kinase C. J Biol Chem 266: 23537-23541, 1991.
78. Jurica MS, Mesecar A, Heath PJ, Shi W, Nowak T, Stoddard BL. The allosteric regulation of pyruvate kinase by fructose-1,6-bisphosphate. Structure 6: 195-210, 1998.
79. Kaelin WG Jr. Cancer and altered metabolism: potential importance of hypoxia-inducible factor and 2-oxoglutarate-dependent dioxygenases. Cold Spring Harbor Symp Quant Biol 76: 335-345, 2011.
80. Kaelin WG Jr, Ratcliffe PJ. Oxygen sensing by metazoans: the central role of the HIF hydroxylase pathway. Mol Cell 30: 393-402, 2008.
81. Kafri R, Levy J, Ginzberg MB, Oh S, Lahav G, Kirschner MW. Dynamics extracted from fixed cells reveal feedback linking cell growth to cell cycle. Nature 494: 480-483, 2013.
82. 2+-dependent exocytosis in pancreatic beta-cells. Diabetes 51, Suppl 1: S19-S24, 2002.
83. Keller KE, Tan IS, Lee YS. SAICAR stimulates pyruvate kinase isoform M2 and promotes cancer cell survival in glucose-limited conditions. Science 338: 1069-1072, 2012.
84. Kim J, Guan KL. Amino acid signaling in TOR activation. Annu Rev Biochem 80: 1001-1032, 2011.
85. Kitaguchi T, Oya M, Wada Y, Tsuboi T, Miyawaki A. Extracellular calcium influx activates adenylate cyclase 1 and potentiates insulin secretion in MIN6 cells. Biochem J 450: 365-373, 2013.
86. Kresnowati MT, van Winden WA, Almering MJ, ten Pierick A, Ras C, Knijnenburg TA, Daran-Lapujade P, Pronk JT, Heijnen JJ, Daran JM. When transcriptome meets metabolome: fast cellular responses of yeast to sudden relief of glucose limitation. Mol Syst Biol 2: 49, 2006.
87. Kuma A, Hatano M, Matsui M, Yamamoto A, Nakaya H, Yoshimori T, Ohsumi Y, Tokuhisa T, Mizushima N. The role of autophagy during the early neonatal starvation period. Nature 432: 1032-1036, 2004.
88. Laplante M, Sabatini DM. mTOR signaling in growth control and disease. Cell 149: 274-293, 2012.
89. Lee J, Kim HK, Han YM, Kim J. Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 in regulating transcription. Int J Biochem Cell Biol 40: 1043-1054, 2008.
90. Lee J, Kim HK, Han YM, Kim J. Pyruvate kinase isozyme type M2 (PKM2) interacts and cooperates with Oct-4 in regulating transcription. Int J Biochem Cell Biol 40: 1043-1054, 2008.
91. Lindstrom P, Sehlin J. Effect of glucose on the intracellular pH of pancreatic islet cells. Biochem J 218: 887-892, 1984.
92. Linehan WM, Srinivasan R, Schmidt LS. The genetic basis of kidney cancer: a metabolic disease. Nat Rev Urol 7: 277-285, 2010.
93. Loewith R, Hall MN. Target of rapamycin (TOR) in nutrient signaling and growth control. Genetics 189: 1177-1201, 2011.
94. Loewith R, Jacinto E, Wullschleger S, Lorberg A, Crespo JL, Bonenfant D, Oppliger W, Jenoe P, Hall MN. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 10: 457-468, 2002.
95. Lunt SY, Vander Heiden MG. Aerobic glycolysis: meeting the metabolic requirements of cell proliferation. Annu Rev Cell Dev Biol 27: 441-464, 2011.
96. Luo W, Hu H, Chang R, Zhong J, Knabel M, O'Meally R, Cole RN, Pandey A, Semenza GL. Pyruvate kinase M2 is a PHD3-stimulated coactivator for hypoxia-inducible factor 1. Cell 145: 732-744, 2011.
97. Luo W, Semenza GL. Emerging roles of PKM2 in cell metabolism and cancer progression. Trends Endocrinol Metab 23: 560-566, 2012.
98. Ma H, Botstein D. Effects of null mutations in the hexokinase genes of Saccharomyces cerevisiae on catabolite repression. Mol Cell Biol 6: 4046-4052, 1986.
99. Ma XM, Blenis J. Molecular mechanisms of mTOR-mediated translational control. Nat Rev Mol Cell Biol 10: 307-318, 2009.
100. MacDonald PE, Joseph JW, Rorsman P. Glucosesensing mechanisms in pancreatic beta-cells. Philos Trans R Soc Lond B Biol Sci 360: 2211-2225, 2005.
101. 2+ in insulin-secreting cells by spectral imaging microscopy. Am J Physiol Cell Physiol 270: C1438-C1446, 1996.
102. Mayer FV, Heath R, Underwood E, Sanders MJ, Carmena D, McCartney RR, Leiper FC, Xiao B, Jing C, Walker PA, Haire LF, Ogrodowicz R, Martin SR, Schmidt MC, Gamblin SJ, Carling D. ADP regulates SNF1, the Saccharomyces cerevisiae homolog of AMP-activated protein kinase. Cell Metab 14: 707-714, 2011.
103. Mazurek S. Pyruvate kinase type M2: a key regulator of the metabolic budget system in tumor cells. Int J Biochem Cell Biol 43: 969-980, 2011.
104. Mazurek S, Boschek CB, Hugo F, Eigenbrodt E. Pyruvate kinase type M2 and its role in tumor growth and spreading. Semin Cancer Biol 15: 300-308, 2005.
105. McCarthy N. Metabolism: unmasking an oncometabolite. Nat Rev Cancer 12: 229, 2012.
106. Meijer AJ, Codogno P. Autophagy: regulation by energy sensing. Curr Biol 21: 227-229, 2011.
107. Moreno F, Herrero P. The hexokinase 2-dependent glucose signal transduction pathway of Saccharomyces cerevisiae. FEMS Microbiol Rev 26: 83-90, 2002.
108. Nichols J, Zevnik B, Anastassiadis K, Niwa H, Klewe-Nebenius D, Chambers I, Schöler H, Smith A. Formation of pluripotent stem cells in the mammalian embryo depends on the POU transcription factor Oct4. Cell 95: 379-391, 1998.
109. Nobukuni T, Joaquin M, Roccio M, Dann SG, Kim SY, Gulati P, Byfield MP, Backer JM, Natt F, Bos JL, Zwartkruis FJ, Thomas G. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc Natl Acad Sci USA 102: 14238-14243, 2005.
110. Noguchi T, Inoue H, Tanaka T. The M1-and M2-type isozymes of rat pyruvate kinase are produced from the same gene by alternative RNA splicing. J Biol Chem 261: 13807-13812, 1986.
111. Novoa I, Zeng H, Harding HP, Ron D. Feedback inhibition of the unfolded protein response by GADD34-mediated dephosphorylation of eIF2alpha. J Cell Biol 153: 1011-1022, 2001.
112. Oldham S, Hafen E. Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol 13: 79-85, 2003.
113. Oliveira AP, Ludwig C, Picotti P, Kogadeeva M, Aebersold R, Sauer U. Regulation of yeast central metabolism by enzyme phosphorylation. Mol Sys Biol 8: 623, 2012.
114. Orij R, Brul S, Smits GJ. Intracellular pH is a tightly controlled signal in yeast. Biochim Biophys Acta 1810: 933-944, 2011.
115. Orij R, Urbanus ML, Vizeacoumar FJ, Giaever G, Boone C, Nislow C, Brul S, Smits GJ. Genomewide analysis of intracellular pH reveals quantitative control of cell division rate by pHc in Saccharomyces cerevisiae. Genome Biol 13: R80, 2012.
116. Peláez R, Fernandez-Garcia P, Herrero P, Moreno F. Nuclear import of the yeast hexokinase 2 protein requires α/β-importin-dependent pathway. J Biol Chem 287: 3518-3529, 2012.
117. Peláez R, Herrero P, Moreno F. Nuclear export of the yeast hexokinase 2 protein requires the Xpo1 (Crm1)-dependent pathway. J Biol Chem 284: 20548-20555, 2009.
118. +-ATPase containing sitedirected mutations. Mol Cell Biol 10: 4110-4115, 1990.
119. Perona R, Serrano R. Increased pH and tumorigenicity of fibroblasts expressing a yeast proton pump. Nature 334: 438-440, 1988.
120. Popova Y, Thayumanavan P, Lonati E, Agrochao M, Thevelein JM. Transport and signaling through the phosphate-binding site of the yeast Pho84 phosphate transceptor. Proc Natl Acad Sci USA 107: 2890-2895, 2010.
121. +-ATPase in fungi and plants. Biochim Biophys Acta 1469: 31-42, 2000.
122. Pulakat L, DeMarco VG, Ardhanari S, Chockalingam A, Gul R, Whaley-Connell A, Sowers JR. Adaptive mechanisms to compensate for overnutrition-induced cardiovascular abnormalities. Am J Physiol Regul Integr Comp Physiol 301: R885-R895, 2011.
123. Rodriguez A, De La Cera T, Herrero P, Moreno F. The hexokinase 2 protein regulates the expression of the GLK1, HXK1 and HXK2 genes of Saccharomyces cerevisiae. Biochem J 355: 625-631, 2001.
124. Rolland F, De Winde JH, Lemaire K, Boles E, Thevelein JM, Winderickx J. Glucose-induced cAMP signalling in yeast requires both a G-protein coupled receptor system for extracellular glucose detection and a separable hexose kinase-dependent sensing process. Mol Microbiol 38: 348-358, 2000.
125. Rolland F, Winderickx J, Thevelein JM. Glucosesensing mechanisms in eukaryotic cells. Trends Biochem Sci 26: 310-317, 2001.
126. + transceptor and its effect on signalling to the PKA and PHO pathways. Biochem J 445: 413-422, 2012.
127. Sancak Y, Bar-Peled L, Zoncu R, Markhard AL, Nada S, Sabatini DM. Ragulator-Rag complex targets mTORC1 to the lysosomal surface and is necessary for its activation by amino acids. Cell 141: 290-303, 2010.
128. Sancak Y, Peterson TR, Shaul YD, Lindquist RA, Thoreen CC, Bar-Peled L, Sabatini DM. The Rag GTPases bind raptor and mediate amino acid signaling to mTORC1. Science 320: 1496-1501, 2008.
129. Serrano R. Effect of ATPase inhibitors on the proton pump of respiratory-deficient yeast. FEBS J 105: 419-424, 1980.
130. Shiojima I, Walsh K. Regulation of cardiac growth and coronary angiogenesis by the Akt/PKB signaling pathway. Genes Dev 20: 3347-3365, 2006.
131. Stoffel M, Duncan SA. The maturity-onset diabetes of the young (MODY1) transcription factor HNF4alpha regulates expression of genes required for glucose transport and metabolism. Proc Natl Acad Sci USA 94: 13209-13214, 1997.
132. Tennessen JM, Baker KD, Lam G, Evans J, Thummel CS. The Drosophila estrogen-related receptor directs a metabolic switch that supports developmental growth. Cell Metab 13: 139-148, 2011.
133. Urano J, Tabancay AP, Yang W, Tamanoi F. The Saccharomyces cerevisiae Rheb G-protein is involved in regulating canavanine resistance and arginine uptake. J Biol Chem 275: 11198-11206, 2000.
134. Urban J, Soulard A, Huber A, Lippman S, Mukhopadhyay D, Deloche O, Wanke V, Anrather D, Ammerer G, Riezman H, Broach JR, De Virgilio C, Hall MN, Loewith R. Sch9 is a major target of TORC1 in Saccharomyces cerevisiae. Mol Cell 26: 663-674, 2007.
135. Van Zeebroeck G, Bonini BM, Versele M, Thevelein JM. Transport and signaling via the amino acid binding site of the yeast Gap1 amino acid transceptor. Nat Chem Biol 5: 45-52, 2009.
136. Vander Heiden MG, Cantley LC, Thompson CB. Understanding the Warburg effect: the metabolic requirements of cell proliferation. Science 324: 1029-1033, 2009.
137. + exchanger isoform 1 (NHE1). Evidence for an additional mechanism not requiring direct phosphorylation. J Biol Chem 269: 5583-5588, 1994.
138. Walther T, Novo M, Rossger K, Letisse F, Loret MO, Portais JC, Francois JM. Control of ATP homeostasis during the respiro-fermentative transition in yeast. Mol Sys Biol 6: 344, 2010.
139. Warburg O. On the origin of cancer cells. Science 123: 309-314, 1956.
140. Ward PS, Thompson CB. Metabolic reprogramming: a cancer hallmark even warburg did not anticipate. Cancer Cell 21: 297-308, 2012.
141. Watanabe R, Tambe Y, Inoue H, Isono T, Haneda M, Isobe KI, Kobayashi T, Hino O, Okabe H, Chano T. GADD34 inhibits mammalian target of rapamycin signaling via tuberous sclerosis complex and controls cell survival under bioenergetic stress. Intl J Mol Med 19: 475-483, 2007.
142. Wellen KE, Thompson CB. A two-way street: reciprocal regulation of metabolism and signalling. Nat Rev Mol Cell Biol 13: 270-276, 2012.
143. Wilson WA, Hawley SA, Hardie DG. Glucose repression/ derepression in budding yeast: SNF1 protein kinase is activated by phosphorylation under derepressing conditions, and this correlates with a high AMP:ATP ratio. Curr Biol 6: 1426-1434, 1996.
144. Wu L, van Dam J, Schipper D, Kresnowati MT, Proell AM, Ras C, van Winden WA, van Gulik WM, Heijnen JJ. Short-term metabolome dynamics and carbon, electron, and ATP balances in chemostat-grown Saccharomyces cerevisiae CEN. PK 113-7D following a glucose pulse. Appl Environ Microbiol 72: 3566-3577, 2006.
145. Xiao B, Heath R, Saiu P, Leiper FC, Leone P, Jing C, Walker PA, Haire L, Eccleston JF, Davis CT, Martin SR, Carling D, Gamblin SJ. Structural basis for AMP binding to mammalian AMP-activated protein kinase. Nature 449: 496-500, 2007.
146. Xiao B, Sanders MJ, Underwood E, Heath R, Mayer FV, Carmena D, Jing C, Walker PA, Eccleston JF, Haire LF, Saiu P, Howell SA, Aasland R, Martin SR, Carling D, Gamblin SJ. Structure of mammalian AMPK and its regulation by ADP. Nature 472: 230-233, 2011.
147. Xu YF, Zhao X, Glass DS, Absalan F, Perlman DH, Broach JR, Rabinowitz JD. Regulation of yeast pyruvate kinase by ultrasensitive allostery independent of phosphorylation. Mol Cell 48: 52-62, 2012.
148. Yang W, Xia Y, Hawke D, Li X, Liang J, Xing D, Aldape K, Hunter T, Alfred Yung WK, Lu Z. PKM2 phosphorylates histone H3 and promotes gene transcription and tumorigenesis. Cell 150: 685-696, 2012.
149. Yang W, Xia Y, Ji H, Zheng Y, Liang J, Huang W, Gao X, Aldape K, Lu Z. Nuclear PKM2 regulates β-catenin transactivation upon EGFR activation. Nature 480: 118-122, 2011.
150. Yang W, Zheng Y, Xia Y, Ji H, Chen X, Guo F, Lyssiotis CA, Aldape K, Cantley LC, Lu Z. ERK1/ 2-dependent phosphorylation and nuclear translocation of PKM2 promotes the Warburg effect. Nat Cell Biol 14: 1295-1304, 2012.
151. Ye J, Mancuso A, Tong X, Ward PS, Fan J, Rabinowitz JD, Thompson CB. Pyruvate kinase M2 promotes de novo serine synthesis to sustain mTORC1 activity and cell proliferation. Proc Natl Acad Sci USA 109: 6904-6909, 2012.
152. Youk H, van Oudenaarden A. Growth landscape formed by perception and import of glucose in yeast. Nature 462: 875-879, 2009.
153. Young BP, Shin JJ, Orij R, Chao JT, Li SC, Guan XL, Khong A, Jan E, Wenk MR, Prinz WA, Smits GJ, Loewen CJ. Phosphatidic acid is a pH biosensor that links membrane biogenesis to metabolism. Science 329: 1085-1088, 2010.
154. Zaman S, Lippman SI, Schneper L, Slonim N, Broach JR. Glucose regulates transcription in yeast through a network of signaling pathways. Mol Sys Biol 5: 245, 2009.
155. Zaman S, Lippman SI, Zhao X, Broach JR. How Saccharomyces responds to nutrients. Annu Rev Genetics 42: 27-81, 2008.
156. Zheng L, Roeder RG, Luo Y. S phase activation of the histone H2B promoter by OCA-S, a coactivator complex that contains GAPDH as a key component. Cell 114: 255-266, 2003.
157. +-ATPase. Science 334: 678-683, 2011.
158. Zoncu R, Efeyan A, Sabatini DM. mTOR: from growth signal integration to cancer, diabetes and ageing. Nat Rev Mol Cell Biol 12: 21-35, 2011.