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  • Original Paper
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A-Raf and Raf-1 work together to influence transient ERK phosphorylation and Gl/S cell cycle progression

Oncogene volume 24, pages 5207–5217 (2005)Cite this article

Abstract

The Raf/MEK/ERK (extracellular regulated kinase) signal transduction pathway controls the ability of cells to respond to proliferative, apoptotic, migratory and differentiation signals. We have investigated the combined contribution of A-Raf and Raf-1 isotypes to signalling through this pathway by generating mice with knockout mutations of both A-raf and raf-1 genes. Double knockout (DKO) mice have a more severe phenotype than single null mutations of either gene, dying in embryogenesis at E10.5. The DKO embryos show no changes in apoptosis, but staining for Ki67 indicates a generalized reduction in proliferation. DKO mouse embryonic fibroblasts (MEFs) exhibit a delayed ability to enter S phase of the cell cycle. This is associated with a reduction in levels of transiently induced MEK and ERK phosphorylation and reduced expression of c-Fos and cyclin Dl. Levels of sustained ERK phosphorylation are not significantly altered. Thus, Raf-1 and A-Raf have a combined role in controlling physiological transient ERK activation and in maintenance of cell cycle progression at its usual rate.

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Acknowledgements

We are extremely grateful to The Wellcome Trust and Cancer Research UK for providing financial support for this project. We thank Mabel Iwobi and Vicky Aldridge for help during the initial stages of this project and Simon Cook for advice on detecting c-Fos.

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Authors and Affiliations

  1. Department of Biochemistry, University of Leicester, 7RH, Adrian Building, University Road, Leicester, LEI, UK

    Kathryn Mercer, Susan Giblett & Catrin Pritchard

  2. Division of Biomedical Services, University of Leicester, 7RH, University Road, Leicester, LEI, UK

    Anthony Oakden & Jane Brown

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

    Richard Marais

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  1. Kathryn Mercer
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Correspondence to Catrin Pritchard.

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Mercer, K., Giblett, S., Oakden, A. et al. A-Raf and Raf-1 work together to influence transient ERK phosphorylation and Gl/S cell cycle progression. Oncogene 24, 5207–5217 (2005). https://doi.org/10.1038/sj.onc.1208707

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