Complexity of the TOR signaling network

Trends in Cell Biology

Volumn 16, Issue 4, 2006, Pages 206-212

  Inoki, Ken ^a   Guan, Kun Liang ^a  

^a UNIVERSITY OF MICHIGAN HEALTH SYSTEM   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

GROWTH FACTOR; PHOSPHATIDYLINOSITOL KINASE; PROTEIN DERIVATIVE; PROTEIN SERINE THREONINE KINASE; RAS HOMOLOG ENRICHED IN BRAIN PROTEIN; TARGET OF RAPAMYCIN KINASE; UNCLASSIFIED DRUG;

CELL GROWTH; DROSOPHILA MELANOGASTER; ENZYME ACTIVATION; ENZYME PHOSPHORYLATION; ENZYME REGULATION; ENZYME SUBSTRATE; EUKARYOTE; FLY; GROWTH REGULATION; HUMAN; MAMMAL; NONHUMAN; NUTRIENT; PRIORITY JOURNAL; PROTEIN FAMILY; PROTEIN FUNCTION; REGULATORY MECHANISM; REVIEW; SIGNAL TRANSDUCTION; STRESS; YEAST;

1-PHOSPHATIDYLINOSITOL 3-KINASE; ANIMALS; CELL COMMUNICATION; CELL ENLARGEMENT; DROSOPHILA PROTEINS; MODELS, BIOLOGICAL; MULTIPROTEIN COMPLEXES; PROTEIN KINASES; SACCHAROMYCES CEREVISIAE PROTEINS; SIGNAL TRANSDUCTION;

DROSOPHILA MELANOGASTER; EUKARYOTA; MAMMALIA;

EID: 33645738458     PISSN: 09628924     EISSN: None     Source Type: Journal    
DOI: 10.1016/j.tcb.2006.02.002     Document Type: Review

References (74)

1. Vezina C., et al. Rapamycin (AY-22,989), a new antifungal antibiotic. I. Taxonomy of the producing streptomycete and isolation of the active principle. J. Antibiot. 28 (1975) 721-726
2. Easton J.B., and Houghton P.J. Therapeutic potential of target of rapamycin inhibitors. Expert Opin. Ther. Targets 8 (2004) 551-564
3. Moses J.W., et al. Sirolimus-eluting stents versus standard stents in patients with stenosis in a native coronary artery. N. Engl. J. Med. 349 (2003) 1315-1323
4. Bjornsti M.A., and Houghton P.J. The TOR pathway: a target for cancer therapy. Nat. Rev. Cancer 4 (2004) 335-348
5. Heitman J., et al. Targets for cell cycle arrest by the immunosuppressant rapamycin in yeast. Science 253 (1991) 905-909
6. Manning G., et al. The protein kinase complement of the human genome. Science 298 (2002) 1912-1934
7. Bakkenist C.J., and Kastan M.B. Initiating cellular stress responses. Cell 118 (2004) 9-17
8. Koltin Y., et al. Rapamycin sensitivity in Saccharomyces cerevisiae is mediated by a peptidyl-prolyl cis-trans isomerase related to human FK506-binding protein. Mol. Cell. Biol. 11 (1991) 1718-1723
9. Chung J., et al. Rapamycin-FKBP specifically blocks growth-dependent activation of and signaling by the 70 kd S6 protein kinases. Cell 69 (1992) 1227-1236
10. Helliwell S.B., et al. TOR1 and TOR2 are structurally and functionally similar but not identical phosphatidylinositol kinase homologues in yeast. Mol. Biol. Cell 5 (1994) 105-118
11. Hay N., and Sonenberg N. Upstream and downstream of mTOR. Genes Dev. 18 (2004) 1926-1945
12. Fingar D.C., et al. Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev. 16 (2002) 1472-1487
13. Montagne J., et al. Drosophila S6 kinase: a regulator of cell size. Science 285 (1999) 2126-2129
14. Gao X., et al. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nat. Cell Biol. 4 (2002) 699-704
15. Hara K., et al. Amino acid sufficiency and mTOR regulate p70 S6 kinase and eIF-4E BP1 through a common effector mechanism. J. Biol. Chem. 273 (1998) 14484-14494
16. Dennis P.B., et al. Mammalian TOR: a homeostatic ATP sensor. Science 294 (2001) 1102-1105
17. Desai B.N., et al. FKBP12-rapamycin-associated protein associates with mitochondria and senses osmotic stress via mitochondrial dysfunction. Proc. Natl. Acad. Sci. U. S. A. 99 (2002) 4319-4324
18. Brugarolas J., et al. Regulation of mTOR function in response to hypoxia by REDD1 and the TSC1/TSC2 tumor suppressor complex. Genes Dev. 18 (2004) 2893-2904
19. Harris T.E., and Lawrence Jr. J.C. TOR signaling. Sci. STKE 2003 (2003) re15
20. Fingar D.C., and 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 (2004) 3151-3171
21. Zheng X.F., et al. TOR kinase domains are required for two distinct functions, only one of which is inhibited by rapamycin. Cell 82 (1995) 121-130
22. Kunz J., et al. Target of rapamycin in yeast, TOR2, is an essential phosphatidylinositol kinase homolog required for G1 progression. Cell 73 (1993) 585-596
23. Schmidt A., et al. The yeast phosphatidylinositol kinase homolog TOR2 activates RHO1 and RHO2 via the exchange factor ROM2. Cell 88 (1997) 531-542
24. Loewith R., et al. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol. Cell 10 (2002) 457-468
25. Reinke A., et al. TOR complex 1 (TORC1) includes a novel component, Tco89p (YPL180w), and cooperates with Ssd1p to maintain cellular integrity in S. cerevisiae. J. Biol. Chem. 279 (2004) 14752-14756
26. Fadri M., et al. The pleckstrin homology domain proteins Slm1 and Slm2 are required for actin cytoskeleton organization in yeast and bind phosphatidylinositol-4,5-bisphosphate and TORC2. Mol. Biol. Cell 16 (2005) 1883-1900
27. Audhya A., et al. Genome-wide lethality screen identifies new PI4,5P2 effectors that regulate the actin cytoskeleton. EMBO J. 23 (2004) 3747-3757
28. Crespo J.L., and Hall M.N. Elucidating TOR signaling and rapamycin action: lessons from Saccharomyces cerevisiae. Microbiol. Mol. Biol. Rev. 66 (2002) 579-591
29. Rudra D., et al. Central role of Ifh1p-Fhl1p interaction in the synthesis of yeast ribosomal proteins. EMBO J. 24 (2005) 533-542
30. Schawalder S.B., et al. Growth-regulated recruitment of the essential yeast ribosomal protein gene activator Ifh1. Nature 432 (2004) 1058-1061
31. Wade J.T., et al. The transcription factor Ifh1 is a key regulator of yeast ribosomal protein genes. Nature 432 (2004) 1054-1058
32. Martin D.E., et al. TOR regulates ribosomal protein gene expression via PKA and the Forkhead transcription factor FHL1. Cell 119 (2004) 969-979
33. Lee T.I., et al. Transcriptional regulatory networks in Saccharomyces cerevisiae. Science 298 (2002) 799-804
34. Brown E.J., et al. Control of p70 s6 kinase by kinase activity of FRAP in vivo. Nature 377 (1995) 441-446
35. Lorenz M.C., and Heitman J. TOR mutations confer rapamycin resistance by preventing interaction with FKBP12-rapamycin. J. Biol. Chem. 270 (1995) 27531-27537
36. Thomas G. The S6 kinase signaling pathway in the control of development and growth. Biol. Res. 35 (2002) 305-313
37. Ruvinsky I., et al. Ribosomal protein S6 phosphorylation is a determinant of cell size and glucose homeostasis. Genes Dev. 19 (2005) 2199-2211
38. Gingras A.C., et al. 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes Dev. 12 (1998) 502-513
39. Haghighat A., et al. Repression of cap-dependent translation by 4E-binding protein 1: competition with p220 for binding to eukaryotic initiation factor-4E. EMBO J. 14 (1995) 5701-5709
40. Beretta L., et al. Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation. EMBO J. 15 (1996) 658-664
41. Kim D.H., et al. mTOR interacts with raptor to form a nutrient-sensitive complex that signals to the cell growth machinery. Cell 110 (2002) 163-175
42. Hara K., et al. Raptor, a binding partner of target of rapamycin (TOR), mediates TOR action. Cell 110 (2002) 177-189
43. Kim D.H., et al. GbetaL, a positive regulator of the rapamycin-sensitive pathway required for the nutrient-sensitive interaction between raptor and mTOR. Mol. Cell 11 (2003) 895-904
44. Schalm S.S., and Blenis J. Identification of a conserved motif required for mTOR signaling. Curr. Biol. 12 (2002) 632-639
45. Choi K.M., et al. 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. 278 (2003) 19667-19673
46. Nojima H., et al. The mammalian target of rapamycin (mTOR) partner, raptor, binds the mTOR substrates p70 S6 kinase and 4E-BP1 through their TOR signaling (TOS) motif. J. Biol. Chem. 278 (2003) 15461-15464
47. Schalm S.S., et al. TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Curr. Biol. 13 (2003) 797-806
48. Oldham S., et al. Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin. Genes Dev. 14 (2000) 2689-2694
49. Sarbassov D.D., et al. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr. Biol. 14 (2004) 1296-1302
50. Jacinto E., et al. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat. Cell Biol. 6 (2004) 1122-1128
51. Nakashima S. Protein kinase C α (PKCα): regulation and biological function. J. Biochem. (Tokyo) 132 (2002) 669-675
52. Sarbassov D.D., et al. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307 (2005) 1098-1101
53. Brazil D.P., and Hemmings B.A. Ten years of protein kinase B signalling: a hard Akt to follow. Trends Biochem. Sci. 26 (2001) 657-664
54. Alessi D.R., et al. Characterization of a 3-phosphoinositide-dependent protein kinase which phosphorylates and activates protein kinase Bα. Curr. Biol. 7 (1997) 261-269
55. Chan T.O., and Tsichlis P.N. PDK2: a complex tail in one Akt. Sci. STKE 2001 (2001) PE1
56. Rane M.J., et al. p38 Kinase-dependent MAPKAPK-2 activation functions as 3-phosphoinositide-dependent kinase-2 for Akt in human neutrophils. J. Biol. Chem. 276 (2001) 3517-3523
57. Feng J., et al. Identification of a PKB/Akt hydrophobic motif Ser-473 kinase as DNA-dependent protein kinase. J. Biol. Chem. 279 (2004) 41189-41196
58. Harrington L.S., et al. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J. Cell Biol. 166 (2004) 213-223
59. Um S.H., et al. Absence of S6K1 protects against age- and diet-induced obesity while enhancing insulin sensitivity. Nature 431 (2004) 200-205
60. Shah O.J., et al. Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Curr. Biol. 14 (2004) 1650-1656
61. Manning B.D., et al. Feedback inhibition of Akt signaling limits the growth of tumors lacking Tsc2. Genes Dev. 19 (2005) 1773-1778
62. Ma L., et al. Genetic analysis of Pten and Tsc2 functional interactions in the mouse reveals asymmetrical haploinsufficiency in tumor suppression. Genes Dev. 19 (2005) 1779-1786
63. Kwiatkowski D.J. Rhebbing up mTOR: new insights on TSC1 and TSC2, and the pathogenesis of tuberous sclerosis. Cancer Biol. Ther. 2 (2003) 471-476
64. Manning B.D., and Cantley L.C. Rheb fills a GAP between TSC and TOR. Trends Biochem. Sci. 28 (2003) 573-576
65. Potter C.J., et al. Akt regulates growth by directly phosphorylating Tsc2. Nat. Cell Biol. 4 (2002) 658-665
66. Dong J., and Pan D. Tsc2 is not a critical target of Akt during normal Drosophila development. Genes Dev. 18 (2004) 2479-2484
67. Radimerski T., et al. dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but requires dPDK1. Nat. Cell Biol. 4 (2002) 251-255
68. Lizcano J.M., et al. Insulin-induced Drosophila S6 kinase activation requires phosphoinositide 3-kinase and protein kinase B. Biochem. J. 374 (2003) 297-306
69. Long X., et al. Rheb binds and regulates the mTOR kinase. Curr. Biol. 15 (2005) 702-713
70. Long X., et al. Rheb binding to mTOR is regulated by amino acid sufficiency. J. Biol. Chem. 280 (2005) 23433-23436
71. Smith E.M., et al. 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 (2005) 18717-18727
72. Urano J., et al. Identification of novel single amino acid changes that result in hyperactivation of the unique GTPase, Rheb, in fission yeast. Mol. Microbiol. 58 (2005) 1074-1086
73. Inoki K., et al. Dysregulation of the TSC-mTOR pathway in human disease. Nat. Genet. 37 (2005) 19-24
74. Kamada Y., et al. Tor2 directly phosphorylates the AGC kinase Ypk2 to regulate actin polarization. Mol. Cell. Biol. 25 (2005) 7239-7248