Re-evaluating AKT regulation: Role of TOR complex 2 in tissue growth

Genes and Development

Volumn 21, Issue 6, 2007, Pages 632-637

  Hietakangas, Ville ^a   Cohen, Stephen M ^a  

^a EUROPEAN MOLECULAR BIOLOGY LABORATORY   (Germany)

Author keywords

AKT; Growth control; Phosphorylation; PI3K

Indexed keywords

PHOSPHATIDYLINOSITOL 3 KINASE; PHOSPHATIDYLINOSITOL 3,4,5 TRISPHOSPHATE 3 PHOSPHATASE; PROTEIN KINASE B BETA; TARGET OF RAPAMYCIN KINASE; TARGET OF RAPAMYCIN KINASE COMPLEX 2; UNCLASSIFIED DRUG;

ANIMAL CELL; ANIMAL EXPERIMENT; ARTICLE; CONTROLLED STUDY; DROSOPHILA; ENZYME ACTIVITY; ENZYME PHOSPHORYLATION; ENZYME REGULATION; GENE; GENE DELETION; HYDROPHOBICITY; HYPERPLASIA; NONHUMAN; PRIORITY JOURNAL; RICTOR GENE; SIGNAL TRANSDUCTION; TISSUE GROWTH;

AMINO ACID SEQUENCE; ANIMALS; DROSOPHILA; DROSOPHILA PROTEINS; GENES, INSECT; MOLECULAR SEQUENCE DATA; MUTATION; PROTO-ONCOGENE PROTEINS C-AKT; SIGNAL TRANSDUCTION; TRANS-ACTIVATORS;

EID: 33947330747     PISSN: 08909369     EISSN: 15495477     Source Type: Journal    
DOI: 10.1101/gad.416307     Document Type: Article

References (35)

1. Alessi, D.R., Andjelkovic, M., Caudwell, B., Cron, P., Morrice, N., Cohen, P., and Hemmings, B.A. 1996. Mechanism of activation of protein kinase B by insulin and IGF-1. EMBO J. 15: 6541-6551.
2. Basler, K. and Struhl, G. 1994. Compartment boundaries and the control of Drosophila limb pattern by hedgehog protein. Nature 368: 208-214.
3. Böhni, R., Riesgo-Escovar, J., Oldham, S., Brogiolo, W., Stocker, H., Andruss, B.F., Beckingham, K., and Hafen, E. 1999. Autonomous control of cell and organ size by CHICO, a Drosophila homolog of vertebrate IRS1-4. Cell 97: 865-875.
4. Brogiolo, W., Stocker, H., Ikeya, T., Rintelen, F., Fernandez, R., and Hafen, E. 2001. An evolutionarily conserved function of the Drosophila insulin receptor and insulin-like peptides in growth control. Curr. Biol. 11: 213-221.
5. Chen, W.S., Xu, P.Z., Gottlob, K., Chen, M.L., Sokol, K., Shiyanova, T., Roninson, I., Weng, W., Suzuki, R., Tobe, K., et al. 2001. Growth retardation and increased apoptosis in mice with homozygous disruption of the Akt1 gene. Genes & Dev. 15: 2203-2208.
6. Cho, H., Mu, J., Kim, J.K., Thorvaldsen, J.L., Chu, Q., Crenshaw III, E.B., Kaestner, K.H., Bartolomei, M.S., Shulman, G.I., and Birnbaum, M.J. 2001a. Insulin resistance and a diabetes mellitus-like syndrome in mice lacking the protein kinase Akt2 (PKB β). Science 292: 1728-1731.
7. Cho, H., Thorvaldsen, J.L., Chu, Q., Feng, F., and Birnbaum, M.J. 2001b. Akt1/PKBα is required for normal growth but dispensable for maintenance of glucose homeostasis in mice. J. Biol. Chem. 276: 38349-38352.
8. Frias, M.A., Thoreen, C.C., Jaffe, J.D., Schroder, W., Sculley, T., Carr, S.A., and Sabatini, D.M. 2006. mSin1 is necessary for Akt/PKB phosphorylation, and its isoforms define three distinct mTORC2s. Curr. Biol. 16: 1865-1870.
9. Gao, X. and Pan, D. 2001. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes & Dev. 15: 1383-1392.
10. Gao, X., Neufeld, T.P., and Pan, D. 2000. Drosophila PTEN regulates cell growth and proliferation through PI3K-dependent and -independent pathways. Dev. Biol. 221: 404-418.
11. Goberdhan, D.C., Paricio, N., Goodman, E.C., Mlodzik, M., and Wilson, C. 1999. Drosophila tumor suppressor PTEN controls cell size and number by antagonizing the Chico/PI3-kinase signaling pathway. Genes & Dev. 13: 3244-3258.
12. Hay, N. 2005. The Akt-mTOR tango and its relevance to cancer. Cancer Cell 8: 179-183.
13. Jacinto, E., Loewith, R., Schmidt, A., Lin, S., Ruegg, M.A., Hall, A., and Hall, M.N. 2004. Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat. Cell Biol. 6: 1122-1128.
14. Jacinto, E., Facchinetti, V., Liu, D., Soto, N., Wei, S., Jung, S.Y., Huang, Q., Qin, J., and Su, B. 2006. SIN1/MIP1 maintains rictor-mTOR complex integrity and regulates Akt phosphorylation and substrate specificity. Cell 127: 125-137.
15. Junger, M.A., Rintelen, F., Stocker, H., Wasserman, J.D., Vegh, M., Radimerski, T., Greenberg, M.E., and Hafen, E. 2003. The Drosophila forkhead transcription factor FOXO mediates the reduction in cell number associated with reduced insulin signaling. J. Biol. 2: 20.
16. Leevers, S.J., Weinkove, D., MacDougall, L.K., Hafen, E., and Waterfield, M.D. 1996. The Drosophila phosphoinositide 3-kinase Dp110 promotes cell growth. EMBO J. 15: 6584-6594.
17. Loewith, R., Jacinto, E., Wullschleger, S., Lorberg, A., Crespo, J.L., Bonenfant, D., Oppliger, W., Jenoe, P., and Hall, M.N. 2002. Two TOR complexes, only one of which is rapamycin sensitive, have distinct roles in cell growth control. Mol. Cell 10: 457-468.
18. Miron, M., Verdu, J., Lachance, P.E., Birnbaum, M.J., Lasko, P.F., and Sonenberg, N. 2001. The translational inhibitor 4E-BP is an effector of PI(3)K/Akt signalling and cell growth in Drosophila. Nat. Cell Biol. 3: 596-601.
19. Newsome, T.P., Asling, B., and Dickson, B.J. 2000. Analysis of Drosophila photoreceptor axon guidance in eye-specific mosaics. Development 127: 851-860.
20. Peng, X.D., Xu, P.Z., Chen, M.L., Hahn-Windgassen, A., Skeen, J., Jacobs, J., Sundararajan, D., Chen, W.S., Crawford, S.E., Coleman, K.G., et al. 2003. Dwarfism, impaired skin development, skeletal muscle atrophy, delayed bone development, and impeded adipogenesis in mice lacking Akt1 and Akt2. Genes & Dev. 17: 1352-1365.
21. Potter, C.J., Huang, H., and Xu, T. 2001. Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 105: 357-368.
22. Puig, O., Marr, M.T., Ruhf, M.L., and Tjian, R. 2003. Control of cell number by Drosophila FOXO: Downstream and feedback regulation of the insulin receptor pathway. Genes & Dev. 17: 2006-2020.
23. Rintelen, F., Stocker, H., Thomas, G., and Hafen, E. 2001. PDK1 regulates growth through Akt and S6K in Drosophila. Proc. Natl. Acad. Sci. 98: 15020-15025.
24. Sarbassov, D.D., Ali, S.M., Kim, D.H., Guertin, D.A., Latek, R.R., Erdjument-Bromage, H., Tempst, P., and Sabatini, D.M. 2004. Rictor, a novel binding partner of mTOR, defines a rapamycin-insensitive and raptor-independent pathway that regulates the cytoskeleton. Curr. Biol. 14: 1296-1302.
25. Sarbassov, D.D., Guertin, D.A., Ali, S.M., and Sabatini, D.M. 2005. Phosphorylation and regulation of Akt/PKB by the rictor-mTOR complex. Science 307: 1098-1101.
26. Shiota, C., Woo, J.T., Lindner, J., Shelton, K.D., and Magnuson, M.A. 2006. Multiallelic disruption of the rictor gene in mice reveals that mTOR complex 2 is essential for fetal growth and viability. Dev. Cell 11: 583-589.
27. Staveley, B.E., Ruel, L., Jin, J., Stambolic, V., Mastronardi, F.G., Heitzler, P., Woodgett, J.R., and Manoukian, A.S. 1998. Genetic analysis of protein kinase B (AKT) in Drosophila. Curr. Biol. 8: 599-602.
28. Stewart, M.J., Berry, C.O., Zilberman, F., Thomas, G., and Kozma, S.C. 1996. The Drosophila p70s6k homolog exhibits conserved regulatory elements and rapamycin sensitivity. Proc. Natl. Acad. Sci. 93: 10791-10796.
29. Tapon, N., Ito, N., Dickson, B.J., Treisman, J.E., and Hariharan, I.K. 2001. The Drosophila tuberous sclerosis complex gene homologs restrict cell growth and cell proliferation. Cell 105: 345-355.
30. Teleman, A.A., Chen, Y.W., and Cohen, S.M. 2005. Drosophila melted modulates FOXO and TOR activity. Dev. Cell 9: 271-281.
31. Thomas, C.C., Deak, M., Alessi, D.R., and van Aalten, D.M. 2002. High-resolution structure of the pleckstrin homology domain of protein kinase b/akt bound to phosphatidylinositol (3,4,5)-trisphosphate. Curr. Biol. 12: 1256-1262.
32. Verdu, J., Buratovich, M.A., Wilder, E.L., and Birnbaum, M.J. 1999. Cellautonomous regulation of cell and organ growth in Drosophila by Akt/PKB. Nat. Cell Biol. 1: 500-506.
33. Weinkove, D., Neufeld, T.P., Twardzik, T., Waterfield, M.D., and Leevers, S.J. 1999. Regulation of imaginal disc cell size, cell number and organ size by Drosophila class I(A) phosphoinositide 3-kinase and its adaptor. Curr. Biol. 9: 1019-1029. [Erratum. 1999. Curr. Biol. 9: R867]
34. Wullschleger, S., Loewith, R., and Hall, M.N. 2006. TOR signaling in growth and metabolism. Cell 124: 471-484.
35. Yang, Q., Inoki, K., Ikenoue, T., and Guan, K.L. 2006. Identification of Sin1 as an essential TORC2 component required for complex formation and kinase activity. Genes & Dev. 20: 2820-2832.