Regulation of TORC1 by Rag GTPases in nutrient response

Nature Cell Biology

Volumn 10, Issue 8, 2008, Pages 935-945

  Kim, Eunjung ^a,c   Goraksha Hicks, Pankuri ^b   Li, Li ^a   Neufeld, Thomas P ^b   Guan, Kun Liang ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF MINNESOTA   (United States)

^c Catholic University of Daegu   (South Korea)

Author keywords

[No Author keywords available]

Indexed keywords

AMINO ACID; GUANOSINE TRIPHOSPHATASE; MAMMALIAN TARGET OF RAPAMYCIN; PROTEIN TORC1; RAG GUANOSINE TRIPHOSPHATASE; TARGET OF RAPAMYCIN COMPLEX 1;

ANIMAL CELL; ANIMAL TISSUE; ARTICLE; AUTOPHAGY; CELL GROWTH; CONTROLLED STUDY; DROSOPHILA MELANOGASTER; GENE EXPRESSION; GENETIC TRANSFECTION; HISTOLOGY; INSECT CELL CULTURE; INSECT GENETICS; MAMMAL CELL; NONHUMAN; PRIORITY JOURNAL; REGULATORY MECHANISM; RNA INTERFERENCE; SIGNAL TRANSDUCTION; STARVATION; WESTERN BLOTTING;

1-PHOSPHATIDYLINOSITOL 3-KINASE; AMINO ACIDS; ANIMALS; AUTOPHAGY; CELL LINE; CELL PROLIFERATION; CELL SIZE; DROSOPHILA MELANOGASTER; DROSOPHILA PROTEINS; FOOD; HUMANS; MONOMERIC GTP-BINDING PROTEINS; RNA, SMALL INTERFERING; SIGNAL TRANSDUCTION;

ANIMALIA; DROSOPHILA MELANOGASTER; MAMMALIA;

EID: 48649085816     PISSN: 14657392     EISSN: None     Source Type: Journal    
DOI: 10.1038/ncb1753     Document Type: Article

References (48)

1. Hay, N. & Sonenberg, N. Upstream and downstream of mTOR. Genes Dev. 18, 1926-1945 (2004).
2. Wullschleger, S., Loewith, R. & Hall, M. N. TOR signaling in growth and metabolism. Cell 124, 471-484 (2006).
3. Sabatini, D. M., Erdjument-Bromage, H., Lui, M., Tempst, P. & Snyder, S. H. RAFT1: A mammalian protein that binds to FKBP12 in a rapamycin-dependent fashion and is homologous to yeast TORs. Cell 78, 35-43 (1994).
4. Jacinto, E. et al. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nature Cell Biol. 6 1122-1128 (2004).
5. Loewith, R. et al. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol. Cell 10, 457-468 (2002).
6. 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, 1296-1302 (2004).
7. Fingar, D. C., Salama, S., Tsou, C., Harlow, E. & Blenis, J. Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev. 16, 1472-1487 (2002).
8. Blommaart, E. F., Luiken, J. J., Blommaart, P. J., van Woerkom, G. M. & Meijer, A. J. Phosphorylation of ribosomal protein S6 is inhibitory for autophagy in isolated rat hepatocytes. J. Biol. Chem. 270, 2320-2326 (1995).
9. Noda, T. & Ohsumi, Y. Tor, a phosphatidylinositol kinase homologue, controls autophagy in yeast. J. Biol. Chem. 273, 3963-3966 (1998).
10. Shigemitsu, K. et al. Regulation of translational effectors by amino acid and mammalian target of rapamycin signaling pathways. Possible involvement of autophagy in cultured hepatoma cells. J. Biol. Chem. 274, 1058-1065 (1999).
11. Gingras, A. C., Kennedy, S. G., O'Leary, M. A., Sonenberg, N. & Hay, N. 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes Dev. 12 502-513 (1998).
12. Thomas, G. The S6 kinase signaling pathway in the control of development and growth. Biol. Res. 35, 305-313 (2002).
13. Inoki, K., Li, Y., Zhu, T., Wu, J. & Guan, K. L. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nature Cell Biol. 4, 648-657 (2002).
14. Manning, B. D., Tee, A. R., Logsdon, M. N., Blenis, J. & Cantley, L. C. 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).
15. Potter, C. J., Pedraza, L. G. & Xu, T. Akt regulates growth by directly phosphorylating Tsc2. Nature Cell Biol. 4, 658-665 (2002).
16. Kwiatkowski, D. J. Rhebbing up mTOR: New insights on TSC1 and TSC2, and the pathogenesis of tuberous sclerosis. Cancer Biol. Ther. 2 471-476 (2003).
17. Long, X., Ortiz-Vega, S., Lin, Y. & Avruch, J. Rheb binding to mammalian target of rapamycin (mTOR) is regulated by amino acid sufficiency. J. Biol. Chem. 280, 23433-23436 (2005).
18. Sancak, Y. et al. PRAS40 is an insulin-regulated inhibitor of the mTORC1 protein kinase. Mol. Cell 25, 903-915 (2007).
19. 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, 14484-14494 (1998).
20. Byfield, M. P., Murray, J. T. & Backer, J. M. hVps34 is a nutrient-regulated lipid kinase required for activation of p70 S6 kinase. J. Biol. Chem. 280, 33076-33082 (2005).
21. Nobukuni, T. et al. Amino acids mediate mTOR/raptor signaling through activation of class 3 phosphatidylinositol 3OH-kinase. Proc. Natl Acad. Sci. USA 102, 14238-14243 (2005).
22. Nakashima, N., Noguchi, E. & Nishimoto, T. Saccharomyces cerevisiae putative G protein, Gtr1p, which forms complexes with itself and a novel protein designated as Gtr2p, negatively regulates the Ran/Gsp1p G protein cycle through Gtr2p. Genetics 152, 853-867 (1999).
23. Bun-Ya, M., Harashima, S. & Oshima, Y. Putative GTP-binding protein, Gtr1, associated with the function of the Pho84 inorganic phosphate transporter in Saccharomyces cerevisiae. Mol. Cell Biol. 12, 2958-2966 (1992).
24. Nakashima, N., Hayashi, N., Noguchi, E. & Nishimoto, T. Putative GTPase Gtr1p genetically interacts with the RanGTPase cycle in Saccharomyces cerevisiae. J. Cell Sci. 109 (Pt 9), 2311-2318 (1996).
25. 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).
26. Gao, M. & Kaiser, C. A. A conserved GTPase-containing complex is required for intracellular sorting of the general amino-acid permease in yeast. Nature Cell Biol. 8, 657-667 (2006).
27. Schurmann, A., Brauers, A., Massmann, S., Becker, W. & Joost, H. G. Cloning of a novel family of mammalian GTP-binding proteins (RagA, RagBs, RagB1) with remote similarity to the Ras-related GTPases. J. Biol. Chem. 270, 28982-28988 (1995).
28. Sekiguchi, T., Hirose, E., Nakashima, N., Ii, M. & Nishimoto, T. Novel G proteins, Rag C and Rag D, interact with GTP-binding proteins, Rag A and Rag B. J. Biol. Chem. 276, 7246-7257 (2001).
29. Hirose, E., Nakashima, N., Sekiguchi, T. & Nishimoto, T. RagA is a functional homologue of S. cerevisiae Gtr1p involved in the Ran/ Gsp1-GTPase pathway. J. Cell Sci. 111, 11-21 (1998).
30. Giot, L. et al. A protein interaction map of Drosophila melanogaster. Science 302, 1727-1736 (2003).
31. Harrington, L. S. et al. The TSC1-2 tumor suppressor controls insulin-PI3K signaling via regulation of IRS proteins. J. Cell Biol. 166, 213-223 (2004).
32. Shah, O. J., Wang, Z. & Hunter, T. Inappropriate activation of the TSC/Rheb/mTOR/S6K cassette induces IRS1/2 depletion, insulin resistance, and cell survival deficiencies. Curr. Biol. 14, 1650-1656 (2004).
33. Sarbassov, D. D., Guertin, D. A., Ali, S. M. & Sabatini, D. M. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307, 1098-1101 (2005).
34. 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. 17, 1829-1834 (2003).
35. Oldham, S., Montagne, J., Radimerski, T., Thomas, G. & Hafen, E. Genetic and biochemical characterization of dTOR, the Drosophila homolog of the target of rapamycin. Genes Dev. 14, 2689-2694 (2000).
36. Zhang, H., Stallock, J. P., Ng, J. C., Reinhard, C. & Neufeld, T. P. Regulation of cellular growth by the Drosophila target of rapamycin dTOR. Genes Dev. 14, 2712-2724 (2000).
37. Colombani, J. et al. A nutrient sensor mechanism controls Drosophila growth. Cell 114, 739-749 (2003).
38. Saucedo, L. J. et al. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nature Cell Biol. 5, 566-571 (2003).
39. Radimerski, T., Montagne, J., Hemmings-Mieszczak, M. & Thomas, G. Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling. Genes Dev. 16, 2627-2632 (2002).
40. Zhang, Y., Billington, Jr., C. J., Pan, D. & Neufeld, T. P. Drosophila target of rapamycin kinase functions as a multimer. Genetics 172, 355-362 (2006).
41. Scott, R. C., Schuldiner, O. & Neufeld, T. P. Role and regulation of starvation-induced autophagy in the Drosophila fat body. Dev. Cell 7, 167-178 (2004).
42. Klionsky, D. J., Cuervo, A. M. & Seglen, P. O. Methods for monitoring autophagy from yeast to human. Autophagy 3, 181-206 (2007).
43. Britton, J. S., Lockwood, W. K., Li, L., Cohen, S. M. & Edgar, B. A. Drosophila's insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions. Dev. Cell 2, 239-249 (2002).
44. Juhasz, G., Erdi, B., Sass, M. & Neufeld, T. P. Atg7-dependent autophagy promotes neuronal health, stress tolerance, and longevity but is dispensable for metamorphosis in Drosophila. Genes Dev. 21, 3061-3066 (2007).
45. Juhasz, G. et al. The class III PI(3)K Vps34 promotes autophagy and endocytosis but not TOR signaling in Drosophila. J. Cell Biol. 181, 655-666 (2008).
46. Clemens, J. C. et al. Use of double-stranded RNA interference in Drosophila cell lines to dissect signal transduction pathways. Proc. Natl Acad. Sci. USA 97, 6499-6503 (2000).
47. Scott, R. C., Juhasz, G. & Neufeld, T. P. Direct induction of autophagy by Atg1 inhibits cell growth and induces apoptotic cell death. Curr. Biol. 17, 1-11 (2007).
48. Hennig, K. M., Colombani, J. & Neufeld, T. P. TOR coordinates bulk and targeted endocytosis in the Drosophila melanogaster fat body to regulate cell growth. J. Cell Biol. 173, 963-974 (2006).