16
Views
192
CrossRef citations to date
0
Altmetric
Research Article

The Insulin-Induced Signalling Pathway Leading to S6 and Initiation Factor 4E Binding Protein 1 Phosphorylation Bifurcates at a Rapamycin-Sensitive Point Immediately Upstream of p70s6k

, , , , &
Pages 5426-5436 | Received 18 Mar 1997, Accepted 30 May 1997, Published online: 29 Mar 2023

REFERENCES

  • Avni, D., S. Shama, F. Loreni, and O. Meyuhas. 1994. Vertebrate mRNAs with a 59-terminal pyrimidine tract are candidates for translational repression in quiescent cells: characterization of the translational cis-regulatory element. Mol. Cell. Biol. 14:3822–3833.
  • Azpiazu, I., A. R. Saltiel, A. A. DePaoli-Roach, and J. C. Lawrence, Jr. 1996. Regulation of both glycogen synthase and PHAS-I by insulin in rat skeletal muscle involves mitogen-activated protein kinase-independent and rapamycin-sensitive pathways. J. Biol. Chem. 271:5033–5039.
  • Bandi, H. R., S. Ferrari, J. Krieg, H. E. Meyer, and G. Thomas. 1993. Identi®cation of 40S ribosomal protein S6 phosphorylation sites in Swiss mouse 3T3 ®broblasts stimulated with serum. J. Biol. Chem. 268:4530–4533.
  • Beretta, L., A.-C. Gingras, Y. V. Svitkin, M. N. Hall, and N. Sonenberg. 1996. Rapamycin blocks the phosphorylation of 4E-BP1 and inhibits cap-dependent initiation of translation. EMBO J. 15:658–664.
  • Bommer, U. A., A. Lazaris-Karatzas, A. DeBenedetti, P. Nurnberg, R. Benndorf, H. Bielka, and N. Sonenberg. 1994. Translational regulation of the mammalian growth-related protein P23: involvement of eIF-4E. Cell. Mol. Biol. Res. 40:633–641.
  • Brown, E. J., M. A. Albers, T. B. Shin, K. Ichikawa, C. T. Keith, W. S. Lane, and S. L. Schreiber. 1994. A mammalian protein targeted by G1-arresting rapamycin-receptor complex. Nature 369:756–758.
  • Brown, E. J., P. A. Beal, C. T. Keith, J. Chen, T. B. Shin, and S.L. Schreiber. 1995. Control of p70 S6 kinase by kinase activity of FRAP in vivo. Nature 377:441–446.
  • Brown, E. J., and S. L. Schreiber. 1996. A signalling pathway to translational control. Cell 86:517–520.
  • Brunn, G. J., J. Williams, C. Sabers, G. Wiederrecht, J. C. Lawrence, Jr., and R. T. Abraham. 1996. Direct inhibition of the signalling functions of the mammalian target of rapamycin by the phosphoinositide 3-kinase inhibitors, wortmannin and LY294002. EMBO J. 15:5256–5267.
  • Chung, J., C. J. Kuo, G. R. Crabtree, and J. Blenis. 1992. Rapamycin-FKBP speci®cally blocks growth-dependent activation of and signalling by the 70 kd S6 protein kinases. Cell 69:1227–1236.
  • Dardevet, D., C. Sornet, T. Vary, and J. Grizard. 1996. Phosphatidylinositol 3-kinase and p70 S6 kinase participate in the regulation of protein turnover in skeletal muscle by insulin and insulin-like growth factor I. Endocrinology 137:4087–4094.
  • DeBenedetti, A., B. Joshi, J. R. Graff, and S. G. Zimmer. 1994. CHO cells transformed by the translation factor eIF4E display increased c-myc expression but require overexpression of Max for tumorigenicity. Mol. Cell. Differ. 2:347–371.
  • Dennis, P. B., N. Pullen, S. C. Kozma, and G. Thomas. 1996. The principal rapamycin-sensitive p70s6k phosphorylation sites T229 and T389 are differentially regulated by rapamycin-insensitive kinase-kinases. Mol. Cell. Biol. 16:6242–6251.
  • DePhilip, R. M., W. A. Rudert, and I. Lieberman. 1980. Preferential stimulation of ribosomal protein synthesis by insulin and in the absence of ribosomal and messenger ribonucleic acid formation. Biochemistry 19:1662–1669.
  • de Vries-Smits, A. M. M., B. M. T. Burgering, S. J. Leevers, C. J. Marshall, and J. L. Bos. 1992. Involvement of p21ras in activation of extracellular signal-regulated kinase 2. Nature 357:602–604.
  • Fagan, R. J., A. Lazaris-Karatzas, N. Sonenberg, and R. Rozen. 1991. Translational control of ornithine aminotransferase: modulation by initiation factor eIF-4E. J. Biol. Chem. 266:16518–16523.
  • Ferrari, S., H. R. Bandi, B. M. Bussian, and G. Thomas. 1991. Mitogen-activated 70K S6 kinase. J. Biol. Chem. 266:22770–22775.
  • Ferrari, S., W. Bannwarth, S. J. Morley, N. F. Totty, and G. Thomas. 1992. Activation of p70s6k is associated with phosphorylation of four clustered sites displaying Ser/Thr-Pro motifs. Proc. Natl. Acad. Sci. USA 89:7282–7285.
  • Ferrari, S., R. B. Pearson, M. Siegmann, S. C. Kozma, and G. Thomas. 1993. The immunosuppressant rapamycin induces inactivation of p70s6k through dephosphorylation of a novel set of sites. J. Biol. Chem. 268:16091–16094.
  • Ferrari, S., and G. Thomas. 1994. S6 phosphorylation and the p70s6k/p85s6k. Crit. Rev. Biochem. Mol. Biol. 29:385–413.
  • Flotow, H., and G. Thomas. 1992. Substrate recognition determinants of the mitogen-activated 70K S6 kinase from rat liver. J. Biol. Chem. 267:3074–3078.
  • Gingras, A.-C., Y. Svitkin, G. J. Belsham, A. Pause, and N. Sonenberg. 1996. Activation of the translational suppressor 4E-BP1 following infection with encephalomyocarditis virus and poliovirus. Proc. Natl. Acad. Sci. USA 93:5578–5583.
  • Hammond, M., and L. H. Bowman. 1988. Insulin stimulates the translation of ribosomal proteins and the transcription of rDNA in mouse myoblasts. J. Biol. Chem. 263:17785–17791.
  • Han, J. W., R. B. Pearson, P. B. Dennis, and G. Thomas. 1995. Rapamycin, wortmannin, and the methylxanthine SQ20006 inactivate p70s6k by inducing dephosphorylation of the same subset of sites. J. Biol. Chem. 270:21396–21403.
  • Haystead, T. A. J., C. M. M. Haystead, C. Hu, T. A. Lin, and J. C. Lawrence, Jr. 1994. Phosphorylation of PHAS-I by mitogen-activated protein (MAP) kinase. J. Biol. Chem. 269:23185–23191.
  • Hunter, T. 1995. When is a lipid kinase not a lipid kinase? When it is a protein kinase. Cell 83:1–4.
  • Jefferies, H. B. J., C. Reinhard, S. C. Kozma, and G. Thomas. 1994. Rapamycin selectively represses translation of the “polypyrimidine tract” mRNA family. Proc. Natl. Acad. Sci. USA 91:4441–4445.
  • Jefferies, H. B. J., G. Thomas, and G. Thomas. 1994. Elongation factor-1a mRNA is selectively translated following mitogenic stimulation. J. Biol. Chem. 269:4367–4372.
  • Jefferies, H. B. J., S. Fumagalli, P. B. Dennis, D. Reinhard, R. B. Pearson, and G. Thomas. 1997. Rapamycin suppresses 59TOp mRNA translation through inhibition of p70s6k, EMBO J. 16:3693–3704.
  • Joshi, B., A.-L. Cai, B. D. Keiper, W. B. Minich, R. Mendez, C. M. Beach, J. Stepinski, R. Stolarski, E. Darzynkiewicz, and R. E. Rhoads. 1995. Phosphorylation of eukaryotic protein synthesis initiation factor 4E at Ser-209. J. Biol. Chem. 270:14597–14603.
  • Kardalinou, E., N. Zhelev, C. A. Hazzalin, and L. C. Mahadevan. 1994. Anisomycin and rapamycin de®ne an area upstream of p70/85S6k containing a bifurcation to histone H3-HMG-like protein phosphorylation and c-fos- c-jun induction. Mol. Cell. Biol. 14:1066–1074.
  • Kato, J. Y., M. Matsuoka, K. Polyak, J. Massague, and C. J. Sherr. 1994. Cyclic AMP-induced G1 phase arrest mediated by an inhibitor (p27kip1) of cyclin-dependent kinase 4 activation. Cell 79:487–496.
  • Kolodziej, P. A., and R. A. Young. 1991. Epitope tagging and protein surveillance. Methods Enzymol. 194:508–519.
  • Krieg, J., J. Hofsteenge, and G. Thomas. 1988. Identi®cation of the 40S ribosomal protein S6 phosphorylation sites induced by cycloheximide. J. Biol. Chem. 263:11473–11477.
  • Krieg, J., A. R. Olivier, and G. Thomas. 1988. Analysis of 40S ribosomal protein S6 phosphorylation during the mitogenic response. Methods Enzymol. 164:575.
  • Kuo, C. J., J. Chung, D. F. Fiorentino, W. M. Flanagan, J. Blenis, and G. R. Crabtree. 1992. Rapamycin selectively inhibits interleukin-2 activation of p70 S6 kinase. Nature 358:70–73.
  • Kyriakis, J. M., and J. Avruch. 1994. S6 kinases and MAP kinases: sequential intermediates in insulin/mitogen-activated protein kinase cascades, p. 84–184. In J. R. Woodgett (ed.), Protein kinases. Oxford University Press, Oxford, United Kingdom.
  • Lane, H. A., A. Fernandez, N. J. C. Lamb, and G. Thomas. 1993. p70s6k function is essential for G1 progression. Nature 363:170–172.
  • Lane, H. A., S. J. Morley, M. Doree, S. C. Kozma, and G. Thomas. 1992. Identi®cation and early activation of a Xenopus laevis p70s6k following progesterone-induced meiotic maturation. EMBO J. 11:1743–1749.
  • Lane, H. A., and G. Thomas. 1991. Puri®cation and properties of mitogen-activated S6 kinase from rat liver and 3T3 cells. Methods Enzymol. 200:269–291.
  • Lin, T., X. Kong, T. A. J. Haystead, A. Pause, G. Belsham, N. Sonenberg, and J. C. Lawrence, Jr. 1994. PHAS-I as a link between mitogen-activated protein kinase and translation initiation. Science 266:653–656.
  • Lin, T. A., X. Kong, A. R. Saltiel, P. J. Blackshear, and J. C. Lawrence, Jr. 1995. Control of PHAS-I by insulin in 3T3-L1 adipocytes. J. Biol. Chem. 270:18531–18538.
  • 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-4g and the translational repressors 4E-binding proteins. Mol. Cell. Biol. 15:4990–4997.
  • Manzella, J. M., W. Rychlik, R. E. Rhoads, J. W. B. Hershey, and P. J. Blackshear. 1991. Insulin induction of ornithine decarboxylase. J. Biol. Chem. 266:2383–2389.
  • Meloche, S., G. Pages, and J. Pouyssegur. 1992. Functional expression and growth factor activation of an epitope-tagged p44 mitogen-activated protein kinase, p44mapk. Mol. Biol. Cell 3:63–71.
  • Mendez, R., M. G. Myers, Jr., M. F. White, and R. E. Rhoads. 1996. 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. 16:2857–2864.
  • Meyuhas, O., D. Avni, and S. Shama. 1996. Translational control of ribosomal protein mRNAs in eukaryotes, p. 363–388. In J. W. B. Hershey, M. B. Mathews, and N. Sonenberg (ed.), Translational control. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
  • Ming, X. F., B. M. T. Burgering, S. Wennstrom, L. Claesson-Welsh, C. H. Heldin, J. L. Bos, S. C. Kozma, and G. Thomas. 1994. Activation of p70/p85 S6 kinase by a pathway independent of p21ras. Nature 371:426–429.
  • Morley, S. J., and G. Thomas. 1993. Intracellular messengers and the control of protein synthesis, p. 447–483. In C. W. Taylor (ed.), The international encyclopedia of pharmacology and therapeutics: intracellular messengers. Pergamon Press, New York, N.Y.
  • Nairn, A. C., and H. C. Palfrey. 1987. Identi®cation of the major Mr 100,000 substrate for calmodulin-dependent protein kinase III in mammalian cells as elongation factor-2. J. Biol. Chem. 262:17299–17303.
  • Nourse, J., E. Firpo, W. M. Flanagan, S. Coats, K. Polyak, M.-H. Lee, J. Massague, G. R. Crabtree, and J. M. Roberts. 1994. Interleukin-2-mediated elimination of the p27Kip cyclin-dependent kinase inhibitor prevented by rapamycin. Nature 372:570–573.
  • Nygard, O., and L. Nilsson. 1990. Translational dynamics. Interactions between the translational factors, tRNA and ribosomes during eukaryotic protein synthesis. Eur. J. Biochem. 191:1–17.
  • Okayama, H., and C. A. Chen. 1988. Calcium phosphate-mediated gene transfer: a highly ef®cient transfection system for stably transforming cells with plasmid DNA. BioTechniques 6:632–638.
  • Pause, A., G. J. Belsham, A.-C. Gingras, O. Donze, T. A. Lin, J. C. Lawrence, Jr., and N. Sonenberg. 1994. Insulin-dependent stimulation of protein synthesis by phosphorylation of a regulator of 59-cap function. Nature 371:762–767.
  • Pearson, R. B., P. B. Dennis, J. W. Han, N. A. Williamson, S. C. Kozma, R. E. H. Wettenhall, and G. Thomas. 1995. The principal target of rapamycin-induced p70s6k inactivation is a novel phosphorylation site within a conserved hydrophobic domain. EMBO J. 14:5279–5287.
  • Price, D. J., J. R. Grove, V. Calvo, J. Avruch, and B. E. Bierer. 1992. Rapamycin-induced inhibition of the 70-kilodalton S6 protein kinase. Science 257:973–977.
  • Proud, C. G. 1994. Turned on by insulin. Nature 371:747–748.
  • Redpath, N. T., E. J. Foulstone, and C. G. Proud. 1996. Regulation of translation elongation factor-2 by insulin via a rapamycin-sensitive signalling pathway. EMBO J. 15:2291–2297.
  • Reinhard, C., A. Fernandez, N. J. C. Lamb, and G. Thomas. 1994. Nuclear localization of p85s6k: functional requirement for entry into S phase. EMBO J. 13:1557–1565.
  • Rosenwald, I. B., R. Kaspar, D. Rousseau, L. Gehrke, P. Leboulch, J. J. Chenn, E. V. Schmidt, N. Sonenberg, and I. M. London. 1995. Eukaryotic translation initiation factor 4E regulates expression of cyclin D1 at transcriptional and post-transcriptional levels. J. Biol. Chem. 270:21176–21180.
  • Sabers, C. J., M. M. Martin, G. J. Brunn, J. M. Williams, F. J. Dumont, G. Weiderrecht, and R. T. Abraham. 1995. Isolation of a protein target of the FKBP12-rapamycin complex in mammalian cells. J. Biol. Chem. 270:815–822.
  • Sanchez, I., R. T. Hughes, B. J. Mayer, K. Yee, J. R. Woodgett, J. Avruch, J. M. Kyriakis, and L. I. Zon. 1994. Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun. Nature 372:794–798.
  • Shama, S., D. Avni, R. M. Frederickson, N. Sonenberg, and O. Meyuhas. 1995. Overexpression of initiation factor eIF-4E does not relieve the translational repression of ribosomal protein mRNAs in quiescent cells. Gene Expr. 4:241–252.
  • Shantz, L. M., and A. E. Pegg. 1994. Overproduction of ornithine decarboxylase caused by relief of translational repression is associated with neoplastic transformation. Cancer Res. 54:2313–2316.
  • Siegmann, M., and G. Thomas. 1987. Separation of multiple phosphorylated forms of 40S ribosomal protein S6 by two dimensional polyacrylamide gel electrophoresis. Methods Enzymol. 146:362–369.
  • Sonenberg, N. 1996. mRNA 59 cap-binding protein eIF4E and control of cell growth, p. 245–269. In J. W. B. Hershey, M. B. Mathews, and N. Sonenberg (ed.), Translational control. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, N.Y.
  • Sun, X. J., P. Rothenberg, C. R. Kahn, J. M. Backer, E. Araki, P. A. Wilden, D. A. Cahill, B. J. Goldstein, and M. F. White. 1991. Structure of the insulin receptor substrate IRS-1 de®nes a unique signal tranduction protein. Nature 352:73–77.
  • Sutherland, C., D. G. Campbell, and P. Cohen. 1993. Identi®cation of insulin stimulated protein kinase-1 as the rabbit equivalent of rskmo-2. Identi®cation of two threonines phosphorylated during activation of mitogen-activated protein kinase. Eur. J. Biochem. 212:581–588.
  • Von Manteuffel, S. R., A.-C. Gingras, X.-F. Ming, N. Sonenberg, and G. Thomas. 1996. 4E-BP1 phosphorylation is mediated by the FRAP-p70s6k pathway and is independent of mitogen-activated protein kinase. Proc. Natl. Acad. Sci. USA 93:4076–4080.
  • Weng, Q.-P., K. Andrabi, M. T. Kozlowski, J. R. Grove, and J. Avruch. 1995. Multiple independent inputs are required for activation of the p70 S6 kinase. Mol. Cell. Biol. 15:2333–2340.
  • Whalen, S. G., A.-C. Gingras, L. Amankwa, S. Mader, P. E. Branton, R. Aebersold, and N. Sonenberg. 1996. Phosphorylation of eIF4E on serine 209 by protein kinase C is inhibited by the translational repressors, 4E-binding proteins. J. Biol. Chem. 271:11831–11837.
  • White, M. F., and C. R. Kahn. 1994. The insulin signalling system. J. Biol. Chem. 269:1–4.
  • Ziemiecki, A., R. G. Muoller, F. Xiao-Chang, N. E. Hynes, and S. Kozma. 1990. Oncogenic activation of the human trk proto-oncogene by recombination with the ribosomal large subunit protein L7a. EMBO J. 9:191–196.

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.