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Differential requirements for ERK1/2 and P38 MAPK activation by thrombin in T cells. Role of P59Fyn and PKCε

Oncogene volume 20, pages 1964–1972 (2001)Cite this article

Abstract

Activation of the mitogen-activated protein kinase (MAPK) cascade is a well documented mechanism for the G-protein-coupled receptors. Here, we have analysed the requirements for ERKs and p38 MAPK activation by thrombin in Jurkat T cells. We show that thrombin-mediated ERKs activation requires both PTK and PKC activities, whereas p38 MAPK activation is dependent only on PTKs. Thrombin-induced ERK and p38 MAPK activation was more pronounced in p56Lck deficient cells indicating that this PTK exerts a negative control on MAPK activity. Accordingly, overexpression of p50 Csk a kinase that inactivates p56Lck induced constitutive activation of ERKs. Requirement for a Src kinase was evidenced by expression of a constitutively active form of p59Fyn in Jurkat cells. Besides its effect on tyrosine phosphorylation events, thrombin also triggered a rapid and robust redistribution of PKCε and δ from the cytosol to the membrane. Expression of constitutively active and dominant negative PKCε demonstrates the pivotal role of this PKC isoform in ERKs activation by thrombin. These data are consistent with a model where thrombin induces ERK activation via both PKC-dependent and independent pathways, whereas p38 MAPK activation requires only PTKs. The PKC-independent pathway requires Src kinases other than p56Lck more likely p59Fyn, while the PKC-dependent mechanism depends on PKCε

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Acknowledgements

This work was supported by INSERM, the University of Nice Sophia Antipolis (BQR), the Association pour la Recherche contre le Cancer (ARC grants 6684 and 9502) and the Ligue Nationale contre le Cancer (Equipe labellisée LNC). We thank Georges Bismuth for helpful suggestions. L Maulon is a fellowship from the Association pour la Recherche contre le Cancer.

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Authors and Affiliations

  1. INSERM U526, 28 Avenue de Valombrose 06107 Nice Cedex 2, France

    Laurence Maulon, Bernard Mari, Corine Bertolotto, Jean Ehrland Ricci, Frederic Luciano, Nathalie Belhacene & Patrick Auberger

  2. INSERM U343, Hopital de l'Archet route de St Antoine de Ginestière, Nice, France

    Marcel Deckert

  3. Institute for Medical Biology and Human Genetics, University of Innsbruck, Innsbruck, A-6020, Austria

    Gottfried Baier

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  1. Laurence Maulon
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Maulon, L., Mari, B., Bertolotto, C. et al. Differential requirements for ERK1/2 and P38 MAPK activation by thrombin in T cells. Role of P59Fyn and PKCε. Oncogene 20, 1964–1972 (2001). https://doi.org/10.1038/sj.onc.1204266

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  • DOI: https://doi.org/10.1038/sj.onc.1204266

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