Recent advances in the regulation of the TOR pathway by insulin and nutrients

Current Opinion in Clinical Nutrition and Metabolic Care

Volumn 8, Issue 1, 2005, Pages 67-72

  Avruch, Joseph ^a   Lin, Yenshou ^a   Long, Xiaomeng ^a   Murthy, Sid ^a   Ortiz Vega, Sara ^a  

^a NONE

Author keywords

LST8; Raptor; Rheb; TOR; Tuberous sclerosis complex

Indexed keywords

HAMARTIN; INSULIN; SOMATOMEDIN; TARGET OF RAPAMYCIN KINASE; TUBERIN;

AMINO ACID DEFICIENCY; CELL ENERGY; CELL GROWTH; DROSOPHILA; ENZYME INACTIVATION; ENZYME REGULATION; NONHUMAN; PROTEIN SYNTHESIS; REVIEW;

GTPASE-ACTIVATING PROTEINS; HUMANS; INSULIN; MONOMERIC GTP-BINDING PROTEINS; NEUROPEPTIDES; PROTEIN KINASES; REPRESSOR PROTEINS; SIGNAL TRANSDUCTION; TUBEROUS SCLEROSIS; TUMOR SUPPRESSOR PROTEINS;

EID: 13444252523     PISSN: 13631950     EISSN: None     Source Type: Journal    
DOI: 10.1097/00075197-200501000-00010     Document Type: Review

References (60)

1. Jacinto E, Hall MN. TOR signalling in bugs, brain and brawn. Nat Rev Mol Cell Biol 2003; 4:117-126. An up-to-date comprehensive review of TOR.
2. 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 2004; 23:3151-3171. An up-to-date comprehensive review of TOR.
3. Hay N, Sonenberg N. Upstream and downstream of mTOR. Genes Dev 2004; 18:1926-1945. An up-to-date comprehensive review of TOR.
4. Burnett PE, Barrow RK, Cohen NA, et al. RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proc Natl Acad Sci U S A 1998; 95:1432-1437.
5. Isotani S, Hara K, Tokunaga C, et al. Immunopurified mammalian target of rapamycin phosphorylates and activates p70 S6 kinase alpha in vitro. J Biol Chem 1999; 274:34 493-34 498.
6. Brunn GJ, Hudson CC, Sekulic A, et al. Phosphorylation of the translational repressor PHAS-I by the mammalian target of rapamycin. Science 1997; 277:99-101.
7. Hara K, Yonezawa K, Weng QP, et al. Amino acid sufficiency and mTOR regulate p70 S6 kinase and elF-4E BP1 through a common effector mechanism. J Biol Chem 1998; 273:14 484-14 494.
8. Weng QP, Andrabi K, Kozlowski MT, et al. Multiple independent inputs are required for activation of the p70 S6 kinase. Mol Cell Biol 1995; 15:2333-2340.
9. Garofalo RS. Genetic analysis of insulin signaling in Drosophila. Trends Endocrinol Metab 2002; 13:156-162.
10. Oldham S, Hafen E. Insulin/IGF and target of rapamycin signaling: a TOR de force in growth control. Trends Cell Biol 2003; 13:79-85. An up-to-date review of IR/IGF-1R and TOR signaling and control of growth in Drosophila.
11. Neufeld TP. Body building: regulation of shape and size by PI3K/TOR signaling during development. Mech Dev 2003; 120:1283-1296. An up-to-date review of IR/IGF-1R and TOR signaling and control of growth in Drosophila.
12. Pan D, Dong J, Zhang Y, Gao X. Tuberous sclerosis complex: from Drosophila to human disease. Trends Cell Biol 2004; 14:78-85. An up-to-date review of IR/IGF-1R and TOR signaling and control of growth in Drosophila.
13. Montagne J, Stewart MJ, Stocker H, et al. Drosophila S6 kinase: a regulator of cell size. Science 1999; 285:2126-2129.
14. Mendez R, Myers MG Jr, White MF, Rhoads RE. Stimulation of protein synthesis, eukaryotic translation initiation factor 4E phosphorylation, and PHAS-I phosphorylation by insulin requires insulin receptor substrate 1 and phosphatidylinositol 3-kinase. Mol Cell Biol 1996; 16:2857-2864.
15. Wang X, Janmaat M, Beugnet A, et al. Evidence that the dephosphorylation of Ser(535) in the epsilon-subunit of eukaryotic initiation factor (elF) 2B is insufficient for the activation of elF2B by insulin. Biochem J 2002; 367:475-481.
16. Tang H, Hornstein E, Stolovich M, et al. Amino acid-induced translation of TOP mRNAs is fully dependent on phosphatidylinositol 3-kinase-mediated signaling, is partially inhibited by rapamycin, and is independent of S6K1 and rpS6 phosphorylation. Mol Cell Biol 2001; 21:8671-8683.
17. Stolovich M, Tang H, Hornstein E, et al. Transduction of growth or mitogenic signals into translational activation of TOP mRNAs is fully reliant on the phosphatidylinositol 3-kinase-mediated pathway but requires neither S6K1 nor rpS6 phosphorylation. Mol Cell Biol 2002; 22:8101-8113.
18. Caldarola S, Amaldi F, Proud CG, Loreni F. Translational regulation of terminal oligopyrimidine mRNAs induced by serum and amino acids involves distinct signaling events. J Biol Chem 2004; 279:13 522-13 531. This describes the PI-3K and amino acid regulation of 5′TOP mRNA expression, which encode much of the translational apparatus.
19. Pende M, Um SH, Mieulet V, et al. S6K1(-/-)/S6K2(-/-) mice exhibit perinatal lethality and rapamycin-sensitive 5′-terminal oligopyrimidine mRNA translation and reveal a mitogen-activated protein kinase-dependent S6 kinase pathway. Mol Cell Biol 2004; 24:3112-3124.
20. Tapon N, Ito N, Dickson BJ, et al. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell 2001; 105:345-355.
21. Potter CJ, Huang H, Xu T. Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 2001; 105:357-368.
22. Gao X, Pan D. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev 2001; 15:1383-1392.
23. Kwiatkowski DJ. Tuberous sclerosis: from tubers to mTOR. Ann Hum Genet 2003; 67:87-96.
24. Krymskaya VP. Tumour suppressors hamartin and tuberin: intracellular signalling. Cell Signal 2003; 15:729-739.
25. Gao X, Zhang Y, Arrazola P, et al. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nat Cell Biol 2002; 4:699-704.
26. Radimerski T, Montagne J, Hemmings-Mieszczak M, Thomas G. Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling. Genes Dev 2002; 16:2627-2632.
27. Kwiatkowski DJ, Zhang H, Bandura JL, et al. A mouse model of TSC1 reveals sex-dependent lethality from liver hemangiomas, and up-regulation of p70S6 kinase activity in Tsc1 null cells. Hum Mol Genet 2002; 11:525-534.
28. Inoki K, Li Y, Zhu T, et al. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 2002; 4:648-657.
29. Tee AR, Fingar DC, Manning BD, et al. Tuberous sclerosis complex-1 and -2 gene products function together to inhibit mammalian target of rapamycin (mTOR)-mediated downstream signaling. Proc Natl Acad Sci U S A 2002; 99:13 571-13 576.
30. Long X, Spycher C, Han ZS, et al. TOR deficiency in C. elegans causes developmental arrest and intestinal atrophy by inhibition of mRNA translation. Curr Biol 2002; 12:1448-1461.
31. Saucedo LJ, Gao X, Chiarelli DA, et al. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat Cell Biol 2003; 5:566-571.
32. Stocker H, Radimerski T, Schindelholz B, et al. Rheb is an essential regulator of S6K in controlling cell growth in Drosophila. Nat Cell Biol 2003; 5:559-565.
33. Patel PH, Thapar N, Guo L, et al. Drosophila Rheb GTPase is required for cell cycle progression and cell growth. J Cell Sci 2003; 116:3601-3610.
34. Zhang Y, Gao X, Saucedo LJ, et al. Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat Cell Biol 2003; 5:578-581.
35. Castro AF, Rebhun JF, Clark GJ, Quilliam LA. Rheb binds tuberous sclerosis complex 2 (TSC2) and promotes S6 kinase a rapamycin- and farnesylation-dependent manner. J Biol Chem 2003; 278:32 493-32 496.
36. Garami A, Zwartkruis FJT, Nobukuni T, et al. Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol Cell 2003; 11:1457-1466.
37. Tee AR, Manning BD, Roux PP, et al. Tuberous sclerosis complex gene products, tuberin and hamartin, control mTOR signaling by acting as a GTPase-activating protein complex toward Rheb. Current Biol 2003; 13:1259-1268.
38. Inoki K, Li Y, Xu T, Guan K-L. Rheb GTPase is a direct target of TSC2 Gap activity and regulates mTOR signaling. Genes Dev 2003; 17:1829-1834.
39. Manning BD, Tee AR, Logsdon MM, et al. Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase/Akt pathway. Mol Cell 2002; 10:151-162.
40. Dan HC, Sun M, Yang L, et al. Phosphatidylinositol 3-kinase/Akt pathway regulates tuberous sclerosis tumor suppressor complex by phosphorylation of tuberin. J Biol Chem 2002; 277:35 364-35 370.
41. Dong J, Pan D. Tsc2 is not a critical target of Akt during normal Drosophila development. Genes Dev 2004; 18:2479-2484.
42. Roux PP, Ballif BA, Anjum R, et al. Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc Natl Acad Sci U S A 2004; 101:13 489-13 494.
43. Dennis PB, Jaeschke A, Saitoh M, et al. Mammalian TOR: a homeostatic ATP sensor. Science 2001; 294:1102-1105.
44. Bolster DR, Crozier SJ, Kimball SR, Jefferson LS. AMP-activated protein kinase suppresses protein synthesis in rat skeletal muscle through down-regulated mammalian target of rapamycin (mTOR) signaling. J Biol Chem 2002; 277:23 977-23 980.
45. Kimura N, Tokunaga C, Dalal S, et al. A possible linkage between AMP-activated protein kinase (AMPK) and mammalian target of rapamycin (mTOR) signalling pathway. Genes Cells 2003; 8:65-79.
46. Inoki K, Zhu T, Guan KL. TSC2 mediates cellular energy response to control cell growth and survival. Cell 2003; 115:577-590. Provides convincing evidence that energy depletion inhibits mTOR signalling through the ability of the AMP-activated protein kinase to phosphorylate TSC2 and upregulate its Rheb-GAP activity.
47. Loewith R, Jacinto E, Wullschleger S, et al. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol Cell 2002; 10:457-468.
48. Kim DH, Sarbassov DD, Ali SM, et al. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 2002; 110:163-175.
49. Hara K, Maruki Y, Long X, et al. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 2002; 110:177-189.
50. Kim DH, Sarbassov D, Ali SM, et al. GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol Cell 2003; 11:895-904.
51. Sarbassov D, Ali SM, Kim DH, et al. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr Biol 2004; 14:1296-1302.
52. Jacinto E, Loewith R, Schmidt A, et al. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 2004; Oct 03 [Epub ahead of print].
53. Schalm SS, Blenis J. Identification of a conserved motif required for mTOR signaling. Curr Biol 2002; 8:632-639.
54. Nojima H, Tokunaga C, Eguchi S, et al. The mammalian target of rapamycin (mTOR) partner, raptor, binds the p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J Biol Chem 2003; 278:15 461-15 464.
55. Choi KM, McMahon LP, Lawrence JC Jr. Two motifs in the translational repressor PHAS-I required for efficient phosphorylation by mammalian target of rapamycin and for recognition by raptor. J Biol Chem 2003; 278:19 667-19 673.
56. Schalm SS, Fingar DC, Sabatini DM, Blenis J. TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation function. Curr Biol 2003; 13:797-806.
57. Beugnet A, Wang X, Proud CG. Target of rapamycin (TOR)-signaling and RAIP motifs play distinct roles in mammalian TOR-dependent phosphorylation of initiation factor 4E-binding. J Biol Chem 2003; 278:40 717-40 722.
58. Oshiro N, Yoshino K, Hidayat S, et al. Dissociation of raptor from mTOR is a mechanism of rapamycin-induced inhibition of mTOR function. Genes Cells 2004; 9:359-366.
59. Mach KE, Furge KA, Albright CF. Loss of Rhb1, a Rheb-related GTPase in fission yeast, causes growth arrest with a terminal phenotype similar to that caused by nitrogen starvation. Genetics 2000; 155:611-622.
60. van Slegtenhorst M, Carr E, Stoyanova R, et al. Tsc1+ and tsc2+ regulate arginine uptake and metabolism in Schizosaccharomyces pombe. J Biol Chem 2004; 279:12 706-12 713.