76
Views
97
CrossRef citations to date
0
Altmetric
Cell Growth and Development

Signaling from Akt to FRAP/TOR Targets both 4E-BP and S6K in Drosophila melanogaster

, &
Pages 9117-9126 | Received 18 Jun 2003, Accepted 16 Sep 2003, Published online: 27 Mar 2023

REFERENCES

  • Backman, S. A., V. Stambolic, A. Suzuki, J. Haight, A. Elia, J. Pretorius, M. S. Tsao, P. Shannon, B. Bolon, G. O. Ivy, and T. W. Mak. 2001. Deletion of PTEN in mouse brain causes seizures, ataxia and defects in soma size resembling Lhermitte-Duclos disease. Nat. Genet. 29: 396–403.
  • Brand, A. H., and N. Perrimon. 1993. Targeted gene expression as a means of altering cell fates and generating dominant phenotypes. Development 118: 401–415.
  • Britton, J. S., W. K. Lockwood, L. Li, S. M. Cohen, and B. A. Edgar. 2002. Drosophila's insulin/PI3-kinase pathway coordinates cellular metabolism with nutritional conditions. Dev. Cell 2: 239–249.
  • Brunn, G. J., P. Fadden, T. A. J. Haystead, and J. C. Lawrence, Jr. 1997. The mammalian target of rapamycin phosphorylates sites having a (Ser/Thr)-Pro motif and is activated by antibodies to a region near its COOH terminus. J. Biol. Chem. 272: 32547–32550.
  • Cho, K. S., J. H. Lee, S. Kim, D. Kim, H. Koh, J. Lee, C. Kim, J. Kim, and J. Chung. 2001. Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway. Proc. Natl. Acad. Sci. USA 98: 6144–6149.
  • Choi, K. M., L. P. McMahon, and J. C. Lawrence, Jr. 2003. 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: 19667–19673.
  • Clemens, J. C., C. A. Worby, N. Simonson-Leff, M. Muda, T. Maehama, B. A. Hemmings, and J. E. Dixon. 2000. Use of double-stranded RNA interference in Drosophila cell lines to dissect signal transduction pathways. Proc. Natl. Acad. Sci. USA 97: 6499–6503.
  • Conlon, I., and M. Raff. 1999. Size control in animal development. Cell 96: 235–244.
  • Dufner, A., M. Andjelkovic, B. M. Burgering, B. A. Hemmings, and G. Thomas. 1999. Protein kinase B localization and activation differentially affect S6 kinase 1 activity and eukaryotic translation initiation factor 4E-binding protein 1 phosphorylation. Mol. Cell. Biol. 19: 4525–4534.
  • Fadden, P., T. A. Haystead, and J. C. Lawrence, Jr. 1997. Identification of phosphorylation sites in the translational regulator, PHAS-I, that are controlled by insulin and rapamycin in rat adipocytes. J. Biol. Chem. 272: 10240–10247.
  • Fingar, D. C., S. Salama, C. Tsou, E. Harlow, and J. Blenis. 2002. Mammalian cell size is controlled by mTOR and its downstream targets S6K1 and 4EBP1/eIF4E. Genes Dev. 16: 1472–1487.
  • Gao, X., and D. Pan. 2001. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev. 15: 1383–1392.
  • Gao, X., Y. Zhang, P. Arrazola, O. Hino, T. Kobayashi, R. S. Yeung, B. Ru, and D. Pan. 2002. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nat. Cell Biol. 4: 699–704.
  • Garami, A., F. J. Zwartkruis, T. Nobukuni, M. Joaquin, M. Roccio, H. Stocker, S. C. Kozma, E. Hafen, J. L. Bos, and G. Thomas. 2003. Insulin activation of Rheb, a mediator of mTOR/S6K/4E-BP signaling, is inhibited by TSC1 and 2. Mol. Cell 11: 1457–1466.
  • Gingras, A. C., S. P. Gygi, B. Raught, R. D. Polakiewicz, R. T. Abraham, M. F. Hoekstra, R. Aebersold, and N. Sonenberg. 1999. Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism. Genes Dev. 13: 1422–1437.
  • Gingras, A. C., S. G. Kennedy, M. A. O'Leary, N. Sonenberg, and N. Hay. 1998. 4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway. Genes Dev. 12: 502–513.
  • Gingras, A. C., B. Raught, S. P. Gygi, A. Niedzwiecka, M. Miron, S. K. Burley, R. D. Polakiewicz, A. Wyslouch-Cieszynska, R. Aebersold, and N. Sonenberg. 2001. Hierarchical phosphorylation of the translation inhibitor 4E-BP1. Genes Dev. 15: 2852–2864.
  • Gingras, A. C., B. Raught, and N. Sonenberg. 2001. Regulation of translation initiation by FRAP/mTOR. Genes Dev. 15: 807–826.
  • Haruta, T., T. Uno, J. Kawahara, A. Takano, K. Egawa, P. M. Sharma, J. M. Olefsky, and M. Kobayashi. 2000. A rapamycin-sensitive pathway down-regulates insulin signaling via phosphorylation and proteasomal degradation of insulin receptor substrate-1. Mol. Endocrinol. 14: 783–794.
  • Heesom, K. J., M. B. Avison, T. A. Diggle, and R. M. Denton. 1998. Insulin-stimulated kinase from rat fat cells that phosphorylates initiation factor-4E binding protein 1 on the rapamycin-insensitive site (serine-111). Biochem. J. 336: 39–48.
  • Inoki, K., Y. Li, T. Xu, and K. L. Guan. 2003. Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling. Genes Dev. 17: 1829–1834.
  • Jaeschke, A., J. Hartkamp, M. Saitoh, W. Roworth, T. Nobukuni, A. Hodges, J. Sampson, G. Thomas, and R. Lamb. 2002. Tuberous sclerosis complex tumor suppressor-mediated S6 kinase inhibition by phosphatidylinositide-3-OH kinase is mTOR independent. J. Cell Biol. 159: 217–224.
  • Kozma, S. C., and G. Thomas. 2002. Regulation of cell size in growth, development and human disease: PI3K, PKB and S6K. Bioessays 24: 65–71.
  • Kwon, C. H., X. Zhu, J. Zhang, L. L. Knoop, R. Tharp, R. J. Smeyne, C. G. Eberhart, P. C. Burger, and S. J. Baker. 2001. PTEN regulates neuronal soma size: a mouse model of Lhermitte-Duclos disease. Nat. Genet. 29: 404–411.
  • Lachance, P. E., M. Miron, B. Raught, N. Sonenberg, and P. Lasko. 2002. Phosphorylation of eukaryotic translation initiation factor 4E is critical for growth. Mol. Cell. Biol. 22: 1656–1663.
  • Lawlor, M. A., A. Mora, P. R. Ashby, M. R. Williams, V. Murray-Tait, L. Malone, A. R. Prescott, J. M. Lucocq, and D. R. Alessi. 2002. Essential role of PDK1 in regulating cell size and development in mice. EMBO J. 21: 3728–3738.
  • Lin, T. A., and J. C. Lawrence, Jr. 1996. Control of the translational regulators PHAS-I and PHAS-II by insulin and cAMP in 3T3-L1 adipocytes. J. Biol. Chem. 271: 30199–30204.
  • Lizcano, J. M., S. Alrubaie, A. Kieloch, M. Deak, S. J. Leevers, and D. R. Alessi. 2003. Insulin-induced Drosophila S6 kinase activation requires phosphoinositide 3-kinase and protein kinase B. Biochem. J. 374: 297–306.
  • Mader, S., H. Lee, A. Pause, and N. Sonenberg. 1995. The translation initiation factor eIF-4E binds to a common motif shared by the translation factor eIF-4γ and the translational repressors 4E-binding proteins. Mol. Cell. Biol. 15: 4990–4997.
  • Marcotrigiano, J., A. C. Gingras, N. Sonenberg, and S. K. Burley. 1999. Cap-dependent translation initiation in eukaryotes is regulated by a molecular mimic of eIF4G. Mol. Cell 3: 707–716.
  • Marygold, S. J., and S. J. Leevers. 2002. Growth signaling: TSC takes its place. Curr. Biol. 12: R785–R787.
  • McManus, E. J., and D. R. Alessi. 2002. TSC1-TSC2: a complex tale of PKB-mediated S6K regulation. Nat. Cell Biol. 4: E214–E216.
  • Miron, M., J. Verdu, P. E. Lachance, M. J. Birnbaum, P. F. Lasko, and N. Sonenberg. 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.
  • Nojima, H., C. Tokunaga, S. Eguchi, N. Oshiro, S. Hidayat, K. Yoshino, K. Hara, N. Tanaka, J. Avruch, and K. Yonezawa. 2003. 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: 15461–15464.
  • Oldham, S., H. Stocker, M. Laffargue, F. Wittwer, M. Wymann, and E. Hafen. 2002. The Drosophila insulin/IGF receptor controls growth and size by modulating PtdInsP(3) levels. Development 129: 4103–4109.
  • Patel, P. H., N. Thapar, L. Guo, M. Martinez, J. Maris, C. L. Gau, J. A. Lengyel, and F. Tamanoi. 2003. Drosophila Rheb GTPase is required for cell cycle progression and cell growth. J. Cell Sci. 116: 3601–3610.
  • Pause, A., G. J. Belsham, A.-C. Gingras, O. Donzé, T. A. Lin, J. C. Lawrence, Jr., and N. Sonenberg. 1994. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 5′-cap function. Nature 371: 762–767.
  • Peng, X.-D., P.-Z. Xu, M.-L. Chen, A. Hahn-Windgassen, J. Skeen, J. Jacobs, D. Sundararajan, W. S. Chen, S. E. Crawford, K. G. Coleman, and N. Hay. 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.
  • Potter, C. J., L. G. Pedraza, and T. Xu. 2002. Akt regulates growth by directly phosphorylating Tsc2. Nat. Cell Biol. 4: 658–665.
  • Poulin, F., A.-C. Gingras, H. Olsen, S. Chevalier, and N. Sonenberg. 1998. 4E-BP3, a new member of the eukaryotic initiation factor 4E-binding protein family. J. Biol. Chem. 273: 14002–14007.
  • Radimerski, T., J. Montagne, M. Hemmings-Mieszczak, and G. Thomas. 2002. Lethality of Drosophila lacking TSC tumor suppressor function rescued by reducing dS6K signaling. Genes Dev. 16: 2627–2632.
  • Radimerski, T., J. Montagne, F. Rintelen, H. Stocker, J. van Der Kaay, C. P. Downes, E. Hafen, and G. Thomas. 2002. dS6K-regulated cell growth is dPKB/dPI(3)K-independent, but requires dPDK1. Nat. Cell Biol. 4: 251–255.
  • Raught, B., A. C. Gingras, and N. Sonenberg. 2000. Regulation of ribosomal recruitment in eukaryotes, p.245–293. In N. Sonenberg, J. W. B., Hershey,, and M. B. Mathews (ed.), Translational control of gene expression. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
  • Rintelen, F., H. Stocker, G. Thomas, and E. Hafen. 2001. PDK1 regulates growth through Akt and S6K in Drosophila. Proc. Natl. Acad. Sci. USA 98: 15020–15025.
  • Saucedo, L., and B. Edgar. 2002. Why size matters: altering cell size. Curr. Opin. Genet. Dev. 12: 565–571.
  • Saucedo, L. J., X. Gao, D. A. Chiarelli, L. Li, D. Pan, and B. A. Edgar. 2003. Rheb promotes cell growth as a component of the insulin/TOR signalling network. Nat. Cell Biol. 5: 566–571.
  • Schalm, S. S., and J. Blenis. 2002. Identification of a conserved motif required for mTOR signaling. Curr. Biol. 12: 632–639.
  • Schalm, S. S., D. C. Fingar, D. M. Sabatini, and J. Blenis. 2003. TOS motif-mediated raptor binding regulates 4E-BP1 multisite phosphorylation and function. Curr. Biol. 13: 797–806.
  • Shioi, T., P. M. Kang, P. S. Douglas, J. Hampe, C. M. Yballe, J. Lawitts, L. C. Cantley, and S. Izumo. 2000. The conserved phosphoinositide 3-kinase pathway determines heart size in mice. EMBO J. 19: 2537–2548.
  • Sigrist, S. J., P. R. Thiel, D. F. Reiff, P. E. D. Lachance, P. Lasko, and C. F. Schuster. 2000. Postsynaptic translation affects the efficacy and morphology of neuromuscular junctions. Nature 405: 1062–1065.
  • Stocker, H., M. Andjelkovic, S. Oldham, M. Laffargue, M. P. Wymann, B. A. Hemmings, and E. Hafen. 2002. Living with lethal PIP3 levels: viability of flies lacking PTEN restored by a PH domain mutation in Akt/PKB. Science 295: 2088–2091.
  • Stocker, H., T. Radimerski, B. Schindelholz, F. Wittwer, P. Belawat, P. Daram, S. Breuer, G. Thomas, and E. Hafen. 2003. Rheb is an essential regulator of S6K in controlling cell growth in Drosophila. Nat. Cell Biol. 5: 559–565.
  • Tee, A. R., and C. G. Proud. 2002. Caspase cleavage of initiation factor 4E-binding protein 1 yields a dominant inhibitor of cap-dependent translation and reveals a novel regulatory motif. Mol. Cell. Biol. 22: 1674–1683.
  • Tuttle, R. L., N. S. Gill, W. Pugh, J. P. Lee, B. Koeberlein, E. E. Furth, K. S. Polonsky, A. Naji, and M. J. Birnbaum. 2001. Regulation of pancreatic beta-cell growth and survival by the serine/threonine protein kinase Akt1/PKBα. Nat. Med. 7: 1133–1137.
  • Wang, X., W. Li, J. L. Parra, A. Beugnet, and C. G. Proud. 2003. The C terminus of initiation factor 4E-binding protein 1 contains multiple regulatory features that influence its function and phosphorylation. Mol. Cell. Biol. 23: 1546–1557.
  • Wang, X., W. Li, M. Williams, N. Terada, D. R. Alessi, and C. G. Proud. 2001. Regulation of elongation factor 2 kinase by p90(RSK1) and p70 S6 kinase. EMBO J. 20: 4370–4379.
  • Weinkove, D., and S. J. Leevers. 2000. The genetic control of organ growth: insights from Drosophila. Curr. Opin. Genet. Dev. 10: 75–80.
  • Zhang, Y., X. Gao, L. J. Saucedo, B. Ru, B. A. Edgar, and D. Pan. 2003. Rheb is a direct target of the tuberous sclerosis tumour suppressor proteins. Nat. Cell Biol. 5: 578–581.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.