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Cell transformation by v-Jun deactivates ERK MAP kinase signalling

Oncogene volume 21, pages 6540–6548 (2002)Cite this article

Abstract

Previous studies have shown that v-Jun accelerates G1 progression and enables cells to sustain S phase entry in the absence of serum growth factors. Since growth factor-dependent ERK MAP kinase signalling plays an important role in regulating the G1/S transition, we investigated whether aberrant ERK regulation might contribute to cell cycle deregulation by v-Jun. Contrary to expectation, we find that cells transformed by v-Jun exhibit a profound reduction in the basal level of active, dual-phosphorylated ERK. In addition, ERK becomes refractory to stimulation by a subset of agonists including serum, LPA, and EGF, but remains partially responsive to the phorbol ester, TPA. Biochemical analysis indicates that these defects are attributable to a combination of inefficient signal propagation between Ras and Raf within the ERK pathway and increased tonic deactivation by MAP kinase phosphatases. Taken together, these results demonstrate that cell transformation by v-Jun induces alterations in cell physiology which antagonize ERK signalling at multiple levels. The potential significance of this phenotype for oncogenesis by v-Jun is discussed.

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References

  • Barnard D, Diaz B, Clawson D, Marshall M . 1998 Oncogene 17: 1539–1547

  • Black EJ, Clark W, Gillespie DA . 2000 Curr. Biol. 10: 1119–1122

  • Brunet A, Roux D, Lenormand P, Dowd S, Keyse S, Pouyssegur J . 1999 EMBO J. 18: 664–674

  • Clark W, Black EJ, MacLaren A, Kruse U, LaThangue N, Vogt PK, Gillespie DA . 2000 Mol. Cell. Biol. 20: 2529–2542

  • Clark W, Gillespie DA . 1997 Cell Growth Differ. 8: 371–380

  • Cowley S, Paterson H, Kemp P, Marshall CJ . 1994 Cell 77: 841–852

  • Fang L, Li G, Liu G, Lee SW, Aaronson SA . 2001 EMBO J. 20: 1931–1939

  • Fu S, Bottoli I, Goller M, Vogt PK . 1999 Proc. Natl. Acad. Sci. USA 96: 5716–5721

  • Fu SL, Waha A, Vogt PK . 2000 Oncogene 19: 3537–3545

  • Keyse SM . 2000 Curr. Opin. Cell. Biol. 12: 186–192

  • Kilbey A, Black EJ, Unlu M, Gillespie DA . 1996 Oncogene 12: 2409–2418

  • Kruse U, Iacovoni JS, Goller ME, Vogt PK . 1997 Proc. Natl. Acad. Sci. USA 94: 12396–12400

  • Lewis TS, Shapiro PS, Ahn NG . 1998 Adv. Cancer Res. 74: 49–139

  • MacLaren A, Clark W, Gillespie DA . 2000 Oncogene 19: 5906–5918

  • Marais R, Light Y, Mason C, Paterson H, Olson MF, Marshall CJ . 1998 Science 280: 109–112

  • Marshall CJ . 1995 Cell 80: 179–185

  • McCarthy SA, Samuels ML, Pritchard CA, Abraham JA, McMahon M . 1995 Genes Dev. 9: 1953–1964

  • Nori M, L'Allemain G, Weber MJ . 1992 Mol. Cell. Biol. 12: 936–945

  • Olson MF, Paterson HF, Marshall CJ . 1998 Nature 394: 295–299

  • Pages G, Lenormand P, L'Allemain G, Chambard JC, Meloche S, Pouyssegur J . 1993 Proc. Natl. Acad. Sci. USA 90: 8319–8323

  • Sahai E, Olson MF, Marshall CJ . 2001 EMBO J. 20: 755–766

  • Sanghera JS, Peter M, Nigg EA, Pelech SL . 1992 Mol. Biol. Cell. 3: 775–787

  • Sewing A, Wiseman B, Lloyd AC, Land H . 1997 Mol. Cell. Biol. 17: 5588–5597

  • Sommer A, Burkhardt H, Keyse SM, Luscher B . 2000 FEBS Lett. 474: 146–150

  • Su HY, Bos TJ, Monteclaro FS, Vogt PK . 1991 Oncogene 6: 1759–1766

  • Taylor SJ, Shalloway D . 1996 Curr. Biol. 6: 1621–1627

  • Treinies I, Paterson HF, Hooper S, Wilson R, Marshall CJ . 1999 Mol. Cell. Biol. 19: 321–329

  • Treisman R . 1994 Curr. Opin. Genet. Dev. 4: 96–101

  • Vogt PK . 2001 Oncogene 20: 2365–2377

  • Woods D, Parry D, Cherwinski H, Bosch E, Lees E, McMahon M . 1997 Mol. Cell. Biol. 17: 5598–5611

  • Zhu J, Woods D, McMahon M, Bishop JM . 1998 Genes Dev. 12: 2997–3007

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Acknowledgements

The authors are grateful to F Mackenzie for the MKP-1 antiserum, to PK Vogt for RCAS-hER and RCAS Δv-JunER, to W Kolch and A Dhillon for reagents and advice on Raf kinase assays, and to JA Wyke and V Cleghon for comments on the manuscript. This work was supported by the UK Cancer Research Campaign (CRC) (now Cancer Research UK).

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Authors and Affiliations

  1. Beatson Institute for Cancer Research, Cancer Research UK Beatson Laboratories, Garscube Estate, Switchback Road, Bearsden, Glasgow, G61 1BD, UK

    Elizabeth J Black, Mark Walker, William Clark & Ann MacLaren

  2. Institute of Biomedical and Life Sciences, University of Glasgow, Glasgow, G12 8QQ, UK

    David A F Gillespie

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  1. Elizabeth J Black
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Correspondence to David A F Gillespie.

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Black, E., Walker, M., Clark, W. et al. Cell transformation by v-Jun deactivates ERK MAP kinase signalling. Oncogene 21, 6540–6548 (2002). https://doi.org/10.1038/sj.onc.1205851

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