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Rap1A protein interferes with various MAP kinase activating pathways in skeletal myogenic cells

Oncogene volume 19, pages 6074–6081 (2000)Cite this article

Abstract

Constitutive expression of the activated Rap1A protein inhibits differentiation of myogenic C2 cells whereas the inactivated Rap1A protein favours cell differentiation and induces late endocytic compartments clustering. Although the role of Rap1A in MAPK activation has been analysed in various cell types, the signalling pathways activated by Rap1A have not been explored in myogenic cells. In this study, we investigated MAP kinase activity in control C2 myoblasts and in stable C2 cell lines expressing mutated Rap1A proteins. We provide evidence that Rap1A mutants promote ERK activation and that the active protein induces a more sustained activation than the inactive protein. In addition, we established that various pathways mediate transient ERK activation in control cells and in cells expressing the inactivated Rap1A protein. In these cells, ERK are activated by a Raf/MEK-dependent pathway, a PI3K/Raf-independent pathway and a third undetermined pathway. In cells expressing the activated Rap1A protein, a PI3K/Raf/MEK-dependent pathway mediates transient ERK activation. However, MAPK activation appears more complex since, according to the state of the myoblasts or the duration of MAPK stimulation, we observed that Rap1A protein could interfere or not with ERK activation.

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Acknowledgements

We particularly express our gratitude to Drs Serge Leibovitch and Marie-Pierre Leibovitch for their encouragement and suggestions. This work was supported in part by the INSERM and the CNRS and in part by a grant from the Association Française de lutte contre les Myopathies (AFM) to V Pizon.

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  1. Institut André Lwoff, UPR 1983, 7 rue Guy Moquet, BP8, 94801, Villejuif, France

    Véronique Pizon

  2. Institut Curie, UMR 2027, Université Paris Sud Bât 110, 91405, Orsay, France

    Giuseppe Baldacci

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  1. Véronique Pizon
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  2. Giuseppe Baldacci
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Pizon, V., Baldacci, G. Rap1A protein interferes with various MAP kinase activating pathways in skeletal myogenic cells. Oncogene 19, 6074–6081 (2000). https://doi.org/10.1038/sj.onc.1203984

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