Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Paper
  • Published:

ERK signalling and oncogene transformation are not impaired in cells lacking A-Raf

Oncogene volume 21, pages 347–355 (2002)Cite this article

Abstract

Previous studies have indicated an important role for the Raf family of protein kinases in controlling cellular responses to extracellular stimuli and activated oncogenes, through their ability to activate the MEK/ERKs. To investigate the specific role of A-Raf in this process we generated A-Raf deficient mouse embryonic fibroblasts (MEFs) and embryonic stem (ES) cells by gene targeting and characterized their ability to undergo proliferation, differentiation, apoptosis, ERK activation, and transformation by oncogenic Ras and Src. The A-Raf deficient cells are not disrupted for any of these processes, despite the fact that this protein is normally expressed at high levels in both cell types. This implies either that A-Raf plays no role in MEK/ERK activation, that its function is fully compensated by other Raf proteins or MEK kinases or that its role in MEK/ERK activation is highly tissue-specific. Interestingly, B-Raf and Raf-1 activity towards MEK as measured by the immunoprecipitation kinase cascade assay are both significantly increased in the A-Raf deficient MEFs.

This is a preview of subscription content, access via your institution

Access options

Buy this article

  • Purchase on Springer Link
  • Instant access to full article PDF
Buy now

Prices may be subject to local taxes which are calculated during checkout

Figure 1
Figure 2
Figure 3
Figure 4
Figure 5

Similar content being viewed by others

References

  • Barnier JV, Papin C, Eychene A, Lecoq O, Calothy G . 1995 J. Biol. Chem. 270: 23381–23389

  • Bogoyevitch MA, Marshall CJ, Sugden PH . 1995 J. Biol. Chem. 270: 26303–26310

  • Daum G, Eisenmann-Tappe I, Fries HW, Troppmair J, Rapp UR . 1994 Trends Biochem. Sci. 19: 474–480

  • Gubbay J, Vivian N, Economou A, Jackson D, Goodfellow P, Lovell-Badge R . 1992 Proc. Natl. Acad. Sci. USA 89: 7953–7957

  • Hagemann C, Kalmes A, Wixler L, Schuster T, Rapp UR . 1997 FEBS Let. 403: 200–202

  • Hagemann C, Rapp UR . 1999 Exp. Cell Res. 253: 34–46

  • Huleihel M, Goldsborough M, Cleveland J, Gunnell M, Bonner T, Rapp UR . 1986 Mol. Cell. Biol. 6: 2655–2662

  • Hüser H, Luckett J, Chiloeches A, Mercer K, Iwobi M, Giblett S, Sun X-M, Brown J, Marais R, Pritchard C . 2001 EMBO J. 20: 1940–1951

  • Kolch W, Heidecker G, Lloyd P, Rapp UR . 1991 Nature 349: 426–428

  • Luckett JCA, Huser MB, Giagtzoglou N, Brown JE, Pritchard CA . 2000 Cell Growth Differ. 11: 163–171

  • Marais R, Light Y, Paterson HF, Mason CS, Marshall CJ . 1997 J. Biol. Chem. 272: 4378–4383

  • Mason CS, Springer CJ, Cooper RG, Superti-Furga G, Marshall CJ, Marais R . 1999 EMBO J. 18: 2137–2148

  • Mikula M, Schreiber M, Husak Z, Kucerova L, Ruth J, Wieser R, Zatloukal K, Beug H, Wagner EF, Baccarini M . 2001 EMBO J. 20: 1952–1962

  • Pritchard CA, Samuels ML, Bosch E, McMahon M . 1995 Mol. Cell. Biol. 15: 6430–6442

  • Pritchard CA, Bolin L, Slattery R, Murray R, McMahon M . 1996 Curr. Biol. 6: 614–617

  • Qureshi SA, Joseph CK, Hendrickson M, Song J, Gupta R, Bruder J, Rapp U, Foster DA . 1993 Biochem. Biophys. Res. Comm. 30: 969–975

  • Samuels ML, Weber MJ, Bishop JM, McMahon M . 1993 Mol. Cell. Biol. 13: 6241–6252

  • Sladek TL, Jacobberger JW . 1992 Oncogene 7: 1305–1313

  • Storm SM, Cleveland JL, Rapp UR . 1990 Oncogene 5: 345–351

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

  • Wojnowski L, Stancato LF, Larner A, Rapp UR, Zimmer A . 2000 Mech. Devel. 91: 97–104

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

  • Yuryev A, Ono M, Goff SA, Macaluso F, Wennogle LP . 2000 Mol. Cell. Biol. 20: 4870–4878

Download references

Acknowledgements

We thank Susan Giblett for embedding and sectioning the teratomas, Mabel Iwobi for the PCR data, Martin McMahon for providing the pZAS4ras and pZAS4src vectors and Lee Topping for help with statistics. We are also grateful to the Division of Biomedical Services at Leicester for their technical assistance. This work was supported by a BBSRC studentship to K Mercer, a Royal Society fellowship to C Pritchard, and project grants from the Medical Research Council and the Cancer Research Campaign. We thank these organisations for their invaluable support.

Author information

Authors and Affiliations

  1. Department of Biochemistry, University of Leicester, University Road, Leicester, LE1 7RH, UK

    Kathryn Mercer, Martin Hüser & Catrin Pritchard

  2. Institute of Cancer Research, 237 Fulham Road, London, SW3 6JB, UK

    Antonio Chiloeches & Richard Marais

  3. Department of Biological Sciences, University of Plymouth, Plymouth, PL4 8AA, UK

    Michelle Kiernan

Authors
  1. Kathryn Mercer
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Antonio Chiloeches
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Martin Hüser
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Michelle Kiernan
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Richard Marais
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Catrin Pritchard
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Catrin Pritchard.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Mercer, K., Chiloeches, A., Hüser, M. et al. ERK signalling and oncogene transformation are not impaired in cells lacking A-Raf. Oncogene 21, 347–355 (2002). https://doi.org/10.1038/sj.onc.1205101

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.onc.1205101

Keywords

This article is cited by

Search

Advanced search

Quick links