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NF-κB is a target of AKT in anti-apoptotic PDGF signalling

Romashkova, Julia A., Makarov, Sergei S.·1999·Nature
DOI 10.1038/43474
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Abstract

The mechanisms of cell proliferation and transformation are intrinsically linked to the process of apoptosis: the default of proliferating cells is to die unless specific survival signals are provided. Platelet-derived growth factor (PDGF) is a principal survival factor that inhibits apoptosis and promotes proliferation, but the mechanisms mediating its anti-apoptotic properties are not completely understood. Here we show that the transcription factor NF-kappaB is important in PDGF signalling. NF-kappaB transmits two signals: one is required for the induction of proto-oncogene c-myc and proliferation, and the second, an anti-apoptotic signal, counterbalances c-Myc cytotoxicity. We have traced a putative pathway whereby PDGF activates NF-kappaB through Ras and phospatidylinositol-3-kinase (PI(3)K) to the PKB/Akt protein kinase and the IkappaB kinase (IKK); NF-kappaB thus appears to be a target of the anti-apoptotic Ras/PI(3)K/Akt pathway. We show that, upon PDGF stimulation, Akt transiently associates in vivo with IKK and induces IKK activation. These findings establish a role for NF-kappaB in growth factor signalling and define an anti-apoptotic Ras/PI(3)K/Akt/IKK/NF-kappaB pathway, thus linking anti-apoptotic signalling with transcription machinery.

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Research works printed but not linked: 30

  1. Harrington,E. A., Bennett,M. R., Fanidi,A. & Evan,G. I. c-Myc-induced apoptosis in fibroblasts is inhibited by specific cytokines. EMBO J. 13, 3286–3295 (1994). · DOI
  2. Evan,G. Cancer—a matter of life and cell death. Int. J. Cancer 71, 709–711 (1997). · DOI
  3. Baldwin, A. S. Jr. The NF-κB and I-κB proteins: new discoveries and insights. Annu. Rev. Immunol. 14, 649–683 (1996). · DOI
  4. Yin Foo,S. & Nolan,G. P. NF-kappaB to the rescue: RELS, apoptosis and cellular transformation. Trends Genet. 15, 229–235 (1999). · DOI
  5. Mercurio,F. & Manning,A. M. Multiple signals converging on NF-kappaB. Curr. Opin. Cell Biol. 11, 226–232 (1999). · DOI
  6. Kauffmann-Zeh,A. et al. Suppression of c-Myc-induced apoptosis by Ras signalling through PI(3)K and PKB. Nature 385, 544–548 (1997). · DOI
  7. Kennedy,S. G. et al. The PI 3-kinase/Akt signaling pathway delivers an anti-apoptotic signal. Genes Dev. 11, 701–713 (1997). · DOI
  8. Evan,G. I. et al. Induction of apoptosis in fibroblasts by c-myc protein. Cell 69, 119–128 (1992). · DOI
  9. Olashaw,N. E., Kowalik,T. F., Huang,E. S. & Pledger,W. J. Induction of NF-κB-like activity by platelet-derived growth factor in mouse fibroblasts. Mol. Biol. Cell 3, 1131–1139 (1992). · DOI
  10. Hinz,M. et al. NF-κB function in growth control: regulation of cyclin D1 expression an dG0/G1-to-S-phase transition. Mol. Cell. Biol. 19, 2690–2698 (1999). · DOI
  11. Kessler,D. J., Duyao,M. P., Spicer,D. B. & Sonenshein,G. E. NF-κB-like factors mediate interleukin 1 induction of c-myc gene transcription in fibroblasts. J. Exp. Med. 176, 787–792 (1992). · DOI
  12. Miagkov,A. V. et al. NF-κB activation provides the potential link between inflammation and hyperplasia in the arthritic joint. Proc. Natl Acad. Sci. USA 95, 13859–13864 (1998). · DOI
  13. Downward,J. Mechanisms and consequences of activation of protein kinase B/Akt. Curr. Opin. Cell Biol. 10, 262–267 (1998). · DOI
  14. Franke,T. F. et al. The protein kinase encoded by the Akt proto-oncogene is a target of the PDGF-activated phosphatidylinositol 3-kinase. Cell 81, 727–736 (1995). · DOI
  15. Mercurio,F. et al. IKK-1 and IKK-2: cytokine-activated IκB kinases essential for NF-κB activation. Science 278, 860–866 (1997). · DOI
  16. Mayo,M. W. et al. Requirement of NF-κB activation to suppress p53-independent apoptosis induced by oncogenic Ras. Science 278, 1812–1815 (1997). · DOI
  17. Marte,B. M., Rodriguez-Viciana,P., Wennstrom,S. Warne,P. H. & Downward,J. R-Ras can activate the phosphoinositide 3-kinase but not the MAP kinase arm of the Ras effector pathways. Curr. Biol. 7, 63–70 (1997). · DOI · Paper page
  18. Firestein,G. S. & Manning,A. M. Signal transduction and transcription factors in rheumatic disease. Arthritis Rheum. 42, 609–621 (1999). · DOI
  19. Datta,S. R. et al. Akt phosphorylation of BAD couples survival signals to the cell-intrinsic death machinery. Cell 91, 231–241 (1997). · DOI · Paper page
  20. del Peso,L., Gonzalez-Garcia,M., Page,C., Herrera,R. & Nunez,G. Interleukin-3-induced phosphorylation of BAD through the protein kinase Akt. Science 278, 687–689 (1997). · DOI · Paper page
  21. Cardone,M. H. et al. Regulation of cell death protease caspase-9 by phosphorylation. Science 282, 1318–1321 (1998). · DOI · Paper page
  22. Brunet,A. et al. Akt promotes cell survival by phosphorylating and inhibiting a Forkhead transcription factor. Cell 96, 857–868 (1999). · DOI · Paper page
  23. Kops,G. J. P. L. et al. Direct control of the Forkhead transcription factor AFX by protein kinase B. Nature 398, 630–634 (1999). · DOI · Paper page
  24. Beraud,C., Henzel,W. J. & Baeuerle,P. A. Involvement of regulatory and catalytic subunits of phosphoinositide 3-kinase in NF-κB activation. Proc. Natl Acad. Sci. USA 96, 429–434 (1999). · DOI
  25. Berra,E. et al. Protein kinase C-ζ isoform is critical for mitogenic signal transduction. Cell 74, 555–563 (1993). · DOI
  26. Sundaresan,M., Yu, Z.-X., Ferrans,V. J., Irani,K. & Finkel,T. Requirement for generation of H2O2 for platelet-derived growth factor signal transduction. Science 270, 296–299 (1995). · DOI · Paper page
  27. Konishi,H., Shinomura,T., Kuroda,S., Ono,Y. & Kikkawa,U. Molecular cloning of rat RAC protein kinase α and β and their association with protein kinase C ζ. Biochem. Biophys. Res. Commun. 205, 817–825 (1994). · DOI
  28. Lallena,M. J., Diaz-Meco,M. T., Bren,G., Paya,C. V. & Moscat,J. Activation of κB kinase beta by protein kinase C isoforms. Mol. Cell. Biol. 19, 2180–2188 (1999). · DOI
  29. Karin,M. & Delhase,M. JNK or IKK, AP-1 or NF-κB, which are the targets for MEK kinase 1 action? Proc. Natl Acad. Sci. USA 95, 9067–9069 (1998). · DOI
  30. Makarov,S. S. et al. Suppression of experimental arthritis by gene transfer of interleukin 1 receptor antagonist cDNA. Proc. Natl Acad. Sci. USA 93, 402–406 (1996). · DOI

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Metadata

Authors
Romashkova, J. A., & Makarov, S. S.
Venue
Nature
Publisher
Springer Science and Business Media LLC
Published
1999-09
Volume
401
Issue
6748
Pages
86-90
ISSN
  • 0028-0836
  • 1476-4687
DOI
10.1038/43474
Cited by
1,517
References
0
Language
en
Licence
www.springer.com/tdm (tdm)

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