ERK and Akt signaling pathways function through parallel mechanisms to promote mTORC1 signaling

American Journal of Physiology - Cell Physiology

Volumn 300, Issue 5, 2011, Pages

  Winter, Jeremiah N ^a   Jefferson, Leonard S ^a   Kimball, Scot R ^a  

^a PENN STATE COLLEGE OF MEDICINE   (United States)

Author keywords

Leucine; Mammalian target of rapamycin; Tuberous sclerosis complex 2

Indexed keywords

GUANOSINE TRIPHOSPHATASE ACTIVATING PROTEIN; INSULIN; LEUCINE; LYSOPHOSPHATIDIC ACID; MAMMALIAN TARGET OF RAPAMYCIN COMPLEX 1; MITOGEN ACTIVATED PROTEIN KINASE; PROTEIN KINASE B; TUBERIN;

ARTICLE; CONTROLLED STUDY; ENZYME PHOSPHORYLATION; FIBROBLAST; PRIORITY JOURNAL; PROTEIN FUNCTION; PROTEIN PROTEIN INTERACTION; SIGNAL TRANSDUCTION;

ANIMALS; CELL LINE; CELLS, CULTURED; EXTRACELLULAR SIGNAL-REGULATED MAP KINASES; FIBROBLASTS; LEUCINE; MICE; PHOSPHORYLATION; PROTEINS; PROTO-ONCOGENE PROTEINS C-AKT; RATS; SIGNAL TRANSDUCTION; TOR SERINE-THREONINE KINASES; TUMOR SUPPRESSOR PROTEINS;

MAMMALIA;

EID: 79955566182     PISSN: 03636143     EISSN: 15221563     Source Type: Journal    
DOI: 10.1152/ajpcell.00504.2010     Document Type: Article

References (60)

1. Abraham RT. Lysosomal Rag-ulation of mTOR complex 1 activity. Cell Metab 11: 341-342, 2010.
2. Anthony JC, Reiter AK, Anthony TG, Crozier SJ, Lang CH, MacLean DA, Kimball SR, Jefferson LS. Orally administered leucine enhances protein synthesis in skeletal muscle of diabetic rats in the absence of increases in 4E-BP1 or S6K1 phosphorylation. Diabetes 51: 928-936, 2002.
3. Balage M, Sinaud S, Prod'Homme M, Dardevet D, Vary TC, Kimball SR, Jefferson LS, Grizard J. Amino acids and insulin are both required to regulate assembly of the eIF4E·eIF4G complex in rat skeletal muscle. Am J Physiol Endocrinol Metab 281: E565-E574, 2001.
4. Bodine SC, Stitt TN, Gonzalez M, Kline WO, Stover GL, Bauerlein R, Zlotchenko E, Scrimgeour A, Lawrence JC, Glass DJ, Yancopoulous GD. Akt/mTOR pathway is a crucial regulator of skeletal muscle hypertrophy and can prevent muscle atrophy in vivo. Nature Cell Biol 3: 1014-1019, 2001.
5. Bueno OF, De Windt LJ, Tymitz KM, Witt SA, Kimball TR, Klevitsky R, Hewett TE, Jones SP, Lefer DJ, Peng CF, Kitsis RN, Molkentin JD. The MEK1-ERK1/2 signaling pathway promotes compensated cardiac hypertrophy in transgenic mice. EMBO J 19: 6341-6350, 2000.
6. Burd NA, West DW, Staples AW, Atherton PJ, Baker JM, Moore DR, Holwerda AM, Parise G, Rennie MJ, Baker SK, Phillips SM. Lowload high volume resistance exercise stimulates muscle protein synthesis more than high-load low volume resistance exercise in young men. PLoS ONE 5: e12033, 2010.
7. Carlson CJ, Fan Z, Gordon SE, Booth FW. Time course of the MAPK and PI3-kinase response within 24 h of skeletal muscle overload. J Appl Physiol 91: 2079-2087, 2001.
8. Carrière A, Cargnello M, Julien LA, Gao H, Bonneil É, Thibault P, Roux PP. Oncogenic MAPK signaling stimulates mTORC1 activity by promoting RSK-mediatedrRaptor phosphorylation. Curr Biol 18: 1269-1277, 2008.
9. Carrière A, Romeo Y, Acosta-Jaquez HA, Moreau J, Bonneil E, Thibault P, Fingar DC, Roux PP. ERK1/2 phosphorylate raptor to promote Ras-dependent activation of mTOR complex 1 (mTORC1). J Biol Chem 286: 567-577, 2011.
10. Dan HC, Sun M, Yang L, Feldman RI, Sui XM, Ou CC, Nellist M, Yeung RS, Halley DJJ, Nicosia SV, Pledger WJ, Cheng JQ. Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin. J Biol Chem 277: 35364-35370, 2002.
11. Drummond MJ, Fry CS, Glynn EL, Dreyer HC, Dhanani S, Timmerman KL, Volpi E, Rasmussen BB. Rapamycin administration in humans blocks the contraction-induced increase in skeletal muscle protein synthesis. J Physiol 587: 1535-1546, 2009.
12. Düvel K, Yecies JL, Menon S, Raman P, Lipovsky AI, Souza AL, Triantafellow E, Ma Q, Gorski R, Cleaver S, Vander Heiden MG, MacKeigan JP, Finan PM, Clish CB, Murphy LO, Manning BD. Activation of a metabolic gene regulatory network downstream of mTOR complex 1. Mol Cell 39: 171-183, 2010.
13. Engelman JA, Chen L, Tan X, Crosby K, Guimaraes AR, Upadhyay R, Maira M, McNamara K, Perera SA, Song Y, Chirieac LR, Kaur R, Lightbown A, Simendinger J, Li T, Padera RF, Garcia-Echeverria C, Weissleder R, Mahmood U, Cantley LC, Wong KK. Effective use of PI3K and MEK inhibitors to treat mutant Kras G12D and PIK3CA H1047R murine lung cancers. Nature Med 14: 1351-1356, 2008.
14. Haar EV, Lee Si Bandhakavi S, Griffin TJ, Kim DH. Insulin signalling to mTOR mediated by the Akt/PKB substrate PRAS40. Nature Cell Biol 9: 316-323, 2007.
15. Heitman J, Movva NR, Hall MN. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253: 905-909, 1991.
16. Herbert TP, Tee AR, Proud CG. The extracellular signal-regulated kinase pathway regulates the phosphorylation of 4E-BP1 at multiple sites. J Biol Chem 277: 11591-11596, 2002.
17. Hoeflich KP, O'Brien C, Boyd Z, Cavet G, Guerrero S, Jung K, Januario T, Savage H, Punnoose E, Truong T, Zhou W, Berry L, Murray L, Amler L, Belvin M, Friedman LS, Lackner MR. In vivo antitumor activity of MEK and phosphatidylinositol 3-kinase inhibitors in basal-like breast cancer models. Clin Cancer Res 15: 4649-4664, 2009.
18. Inoki K, Li Y, Xu T, Guan KL. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev 17: 1829-1834, 2003.
19. Inoki K, Zhu T, Guan KL. TSC2 mediates cellular energy response to control cell growth and survival. Cell 115: 577-590, 2003.
20. Jacinto E, Loewith R, Schmidt A, Lin S, Ruegg MA, Hall A, Hall MN. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nature Cell Biol 6: 1122-1128, 2004.
21. Kim E, Guan KL. RAG GTPases in nutrient-mediated TOR signaling pathway. Cell Cycle 8: 1014-1018, 2009.
22. Kim SH, Roth KA, Moser AR, Gordon JI. Transgenic mouse models that explore the multistep hypothesis of intestinal neoplasia. J Cell Biol 123: 877-893, 1993.
23. Kimball SR, Siegfried BA, Jefferson LS. Glucagon represses signaling through the mammalian target of rapamycin in rat liver by activating AMP-activated protein kinase. J Biol Chem 279: 54103-54109, 2004.
24. Kubica N, Crispino JL, Gallagher JW, Kimball SR, Jefferson LS. Activation of the mammalian target of rapamycin complex 1 is both necessary and sufficient to stimulate eukaryotic initiation factor 2Bε mRNA translation and protein synthesis. Int J Biochem Cell Biol 40: 2522-2533, 2008.
25. Kwiatkowski DJ. Rhebbing up mTOR. New insights on TSC1 and TSC2, and the pathogenesis of tuberous sclerosis. Cancer Biol Ther 2: 471-476, 2003.
26. Laplante M, Sabatini DM. An emerging role of mTOR in lipid biosynthesis. Curr Biol 19: R1046-R1052, 2009.
27. Laplante M, Sabatini DM. mTOR signaling at a glance. J Cell Sci 122: 3589-3594, 2009.
28. Liu Z, Hou P, Ji M, Guan H, Studeman K, Jensen K, Vasko V, El-Naggar AK, Xing M. Highly prevalent genetic alterations in receptor tyrosine kinases and phosphatidylinositol 3-kinase/Akt and mitogen-activated protein kinase pPathways in anaplastic and follicular thyroid cancers. J Clin Endocrinol Metab 93: 3106-3116, 2008.
29. Long X, Lin Y, Ortiz-Vega S, Yonezawa K, Avruch J. Rheb binds and regulates the mTOR kinase. Curr Biol 15: 702, 2005.
30. Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP. Phosphorylation and functional inactivation of TSC2 by Erk: Implications for tuberous sclerosis and cancer pathogenesis. Cell 121: 179-193, 2005.
31. Ma L, Teruya-Feldstein J, Bonner P, Bernardi R, Franz DN, Witte D, Cordon-Cardo C, Pandolfi PP. Identification of S664 TSC2 phosphorylation as a marker for extracellular signal-regulated kinase mediated mTOR activation in tuberous sclerosis and human cancer. Cancer Res 67: 7106-7112, 2007.
32. Manning BD, Tee AR, Logsdon MN, Blenis J, Cantley LC. 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: 151-162, 2002.
33. Montagne J, Stewart MJ, Stocker H, Hafen E, Kozma SC, Thomas G. Drosophila S6 kinase: a regulator of cell size. Science 285: 2126-2129, 1999.
34. Nave BT, Ouwens DM, Withers DJ, Alessi DR, Shepherd PR. Mammalian target of rapamycin is a direct target for protein kinase B: Identification of a convergence point for opposing effects of insulin and amino acid deficiency on protein translation. Biochem J 344: 427-431, 1999.
35. Pallafacchina G, Calabria E, Serrano A, Kalhovde JM, Schiaffino S. A protein kinase B-dependent and rapamycin-sensitive pathway controls skeletal muscle growth but not fiber type specification. Proc Natl Acad Sci USA 99: 9213-9218, 2002.
36. Polak P, Cybulski N, Feige JN, Auwerx J, R, Egg MA, Hall MN. Adipose-specific knockout of raptor results in lean mice with enhanced mitochondrial respiration. Cell Metab 8: 399-410, 2008.
37. Polak P, Hall MN. mTOR and the control of whole body metabolism. Curr Opinion Cell Biol 21: 209-218, 2009.
38. Potter CJ, Pedraza LG, Xu T. Akt regulates growth by directly phosphorylating Tsc2. Nature Cell Biol 4: 658-665, 2002.
39. Rommel C, Bodine SC, Clarke BA, Rossman R, Nunez L, Stitt TN, Yancopoulous GD, Glass DJ. Mediation of IGF-1-induced skeletal myotube hypertrophy by PI(3)K/Akt/mTOR and PI(3)K/Akt/GSK3 pathways. Nature Cell Biol 3: 1009-1013, 2001.
40. Ruvinsky I, Sharon N, Lerer T, Cohen H, Stolovich-Rain M, Nir T, Dor Y, Zisman P, Meyuhas O. Ribosomal protein S6 phosphorylation is a determinant of cell size and glucose homeostasis. Genes Dev 19: 2199-2211, 2005.
41. 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.
42. 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.
43. Sancak Y, Sarbassov DD, Ali SM, Kim DH, Guertin DA, Latek RR, Erdjument-Bromage H, Tempst P, Sabatini DM. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 14: 1296-1302, 2004.
44. She QB, Halilovic E, Ye Q, Zhen W, Shirasawa S, Sasazuki T, Solit DB, Rosen N. 4E-BP1 is a key effector of the oncogenic activation of the Akt and ERK signaling pathways that integrates their function in tumors. Cancer Cell 18: 39-51, 2010.
45. She QB, Solit DB, Ye Q, O'Reilly KE, Lobo J, Rosen N. The BAD protein integrates survival signaling by EGFR/MAPK and PI3K/Akt kinase pathways in PTEN-deficient tumor cells. Cancer Cell 8: 287-297, 2005.
46. Shi H, Scheffler JM, Zeng C, Pleitner JM, Hannon KM, Grant AL, Gerrard DE. Mitogen-activated protein kinase signaling is necessary for the maintenance of skeletal muscle mass. Am J Physiol Cell Physiol 296: C1040-C1048, 2009.
47. Shi H, Zeng C, Ricome A, Hannon KM, Grant AL, Gerrard DE. Extracellular signal-regulated kinase pathway is differentially involved in β-agonist-induced hypertrophy in slow and fast muscles. Am J Physiol Cell Physiol 292: C1681-C1689, 2007.
48. Shima H, Pende M, Chen Y, Fumagalli S, Thomas G, Kozma SC. Disruption of the p70(S6k)/p85(S6k) gene reveals a small mouse phenotype and a new functional S6 kinase. EMBO J 17: 6649-6659, 1998.
49. Simi L, Pratesi N, Vignoli M, Sestini R, Cianchi F, Valanzano R, Nobili S, Mini E, Pazzagli M, Orlando C. High-resolution melting analysis for rapid detection of KRAS, BRAF, and PIK3CA gene mutations in colorectal cancer. Am J Clin Pathol 130: 247-253, 2008.
50. Smith EM, Finn SG, Tee AR, Browne GJ, Proud CG. The tuberous sclerosis protein TSC2 is not required for the regulation of the mammalian target of rapamycin by amino acids and certain cellular stresses. J Biol Chem 280: 18717-18727, 2005.
51. Tsao H, Goel V, Wu H, Yang G, Haluska FG. Genetic interaction between NRAS and BRAF mutations and PTEN//MMAC1 inactivation in melanoma. J Invest Dermatol 122: 337-341, 2004.
52. Ueyama T, Kawashima S, Sakoda T, Rikitake Y, Ishida T, Kawai M, Yamashita T, Ishido S, Hotta H, Yokoyama M. Requirement of activation of the extracellular signal-regulated kinase cascade in myocardial cell hypertrophy. J Mol Cell Cardiol 32: 947-960, 2000.
53. Wang L, Proud CG. Ras/Erk signaling is essential for activation of protein synthesis by Gq protein-coupled receptor agonists in adult cardiomyocytes. Circ Res 91: 821-829, 2002.
54. Wang X, Proud CG. Nutrient control of TORC1, a cell-cycle regulator. Trends Cell Biol 19: 260-267, 2009.
55. Wee S, Jagani Z, Xiang KX, Loo A, Dorsch M, Yao YM, Sellers WR, Lengauer C, Stegmeier F. PI3K pathway activation mediates resistance to MEK inhibitors in KRAS mutant cancers. Cancer Res 69: 4286-4293, 2009.
56. Widegren U, Wretman C, Lionikas A, Hedin G, Henriksson J. Influence of exercise intensity on ERK/MAP kinase signalling in human skeletal muscle. Pflügers Arch 441: 317-322, 2000.
57. Winter JN, Fox TE, Kester M, Jefferson LS, Kimball SR. Phosphatidic acid mediates activation of mTORC1 through the ERK signaling pathway. Am J Physiol Cell Physiol 299: C335-C344, 2010.
58. Yoshida T, Semprun-Prieto L, Sukhanov S, Delafontaine P. IGF-1 prevents ANG II-induced skeletal muscle atrophy via Akt-and Foxodependent inhibition of the ubiquitin ligase atrogin-1 expression. Am J Physiol Heart Circ Physiol 298: H1565-H1570, 2010.
59. Yu K, Toral-Barza L, Shi C, Zhang WG, Zask A. Response and determinants of cancer cell susceptibility to PI3K inhibitors: combined targeting of PI3K and Mek1 as an effective anticancer strategy. Cancer Biol Ther 7: 307-315, 2008.
60. Zhang HH, Huang J, Duvel K, Boback B, Wu S, Squillace RM, Wu CL, Manning BD. Insulin stimulates adipogenesis through the Akt-TSC2-mTORC1 pathway. PLoS One 4: e6189, 2009.