The non-classical MAP kinase ERK3 controls T cell activation.
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.
Maisonneuve-Rosemont Hospital Research Centre, Montreal, Quebec, Canada ; Department of Microbiology, Infectiology and Immunology, University of Montreal, Quebec, Canada.
Miriam
M
Marquis
Maisonneuve-Rosemont Hospital Research Centre, Montreal, Quebec, Canada.
Salix
S
Boulet
Institute of Research in Immunology and Cancer, University of Montreal, Quebec, Canada.
Simon
S
Mathien
Department of Pharmacology and Molecular Biology, University of Montreal, Quebec, Canada ; Institute of Research in Immunology and Cancer, University of Montreal, Quebec, Canada.
Justine
J
Rousseau
Maisonneuve-Rosemont Hospital Research Centre, Montreal, Quebec, Canada.
Paméla
P
Thébault
Maisonneuve-Rosemont Hospital Research Centre, Montreal, Quebec, Canada.
Jean-François
JF
Daudelin
Maisonneuve-Rosemont Hospital Research Centre, Montreal, Quebec, Canada.
Julie
J
Rooney
Department of Pharmacology and Molecular Biology, University of Montreal, Quebec, Canada ; Institute of Research in Immunology and Cancer, University of Montreal, Quebec, Canada.
Benjamin
B
Turgeon
Maisonneuve-Rosemont Hospital Research Centre, Montreal, Quebec, Canada.
Claudine
C
Beauchamp
Department of Pharmacology and Molecular Biology, University of Montreal, Quebec, Canada ; Institute of Research in Immunology and Cancer, University of Montreal, Quebec, Canada.
Sylvain
S
Meloche
Maisonneuve-Rosemont Hospital Research Centre, Montreal, Quebec, Canada ; Department of Microbiology, Infectiology and Immunology, University of Montreal, Quebec, Canada ; Department of Medicine, University of Montreal, Quebec, Canada.
Nathalie
N
Labrecque
D000818:Animals; D049109:Cell Proliferation; D016207:Cytokines / Q000378:metabolism; D017931:DNA Primers / Q000235:genetics; D005434:Flow Cytometry; D005786:Gene Expression Regulation / Q000276:immunology*; D007111:Immunity, Cellular / Q000276:immunology*; D015151:Immunoblotting; D047468:Immunoprecipitation; D008213:Lymphocyte Activation / Q000276:immunology*; D051379:Mice; D048053:Mitogen-Activated Protein Kinase 6 / Q000172:deficiency / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013601:T-Lymphocytes / Q000276:immunology* / Q000378:metabolism; D001616:beta-Galactosidase
D016207:Cytokines; D017931:DNA Primers; D048053:Mitogen-Activated Protein Kinase 6; D001616:beta-Galactosidase