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The Non-Classical MAP Kinase ERK3 Controls T Cell Activation |
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| Authors: | Miriam Marquis Salix Boulet Simon Mathien Justine Rousseau Paméla Thébault Jean-Fran?ois Daudelin Julie Rooney Benjamin Turgeon Claudine Beauchamp Sylvain Meloche Nathalie Labrecque |
| Affiliation: | 1. Maisonneuve-Rosemont Hospital Research Centre, Montreal, Quebec, Canada.; 2. Department of Microbiology, Infectiology and Immunology, University of Montreal, Quebec, Canada.; 3. Department of Pharmacology and Molecular Biology, University of Montreal, Quebec, Canada.; 4. Department of Medicine, University of Montreal, Quebec, Canada.; 5. Institute of Research in Immunology and Cancer, University of Montreal, Quebec, Canada.; Oklahoma Medical Research Foundation, United States of America, |
| Abstract: | The classical mitogen-activated protein kinases (MAPKs) ERK1 and ERK2 are activated upon stimulation of cells with a broad range of extracellular signals (including antigens) allowing cellular responses to occur. ERK3 is an atypical member of the MAPK family with highest homology to ERK1/2. Therefore, we evaluated the role of ERK3 in mature T cell response. Mouse resting T cells do not transcribe ERK3 but its expression is induced in both CD4+ and CD8+ T cells following T cell receptor (TCR)-induced T cell activation. This induction of ERK3 expression in T lymphocytes requires activation of the classical MAPK ERK1 and ERK2. Moreover, ERK3 protein is phosphorylated and associates with MK5 in activated primary T cells. We show that ERK3-deficient T cells have a decreased proliferation rate and are impaired in cytokine secretion following in vitro stimulation with low dose of anti-CD3 antibodies. Our findings identify the atypical MAPK ERK3 as a new and important regulator of TCR-induced T cell activation. |
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