title: The atypical MAPK ERK3 controls positive selection of thymocytes.
abstract: Extracellular signal-regulated kinase 3 (ERK3 )is an atypical member of the mitogen-activated protein kinase (MAPK) family. We have previously shown that ERK3 is expressed during thymocyte differentiation and that its expression is induced in mature peripheral T cells following activation of ERK1/2 by T-cell receptor (TCR) signalling. Herein, we have investigated whether ERK3 expression is required for proper T-cell selection. Using a knock-in mouse model in which the coding sequence of ERK3 is replaced by the gene encoding for the β-galactosidase reporter, we show that ERK3 is expressed by double-positive (DP) thymocytes undergoing positive selection. In ERK3-deficient mice with a polyclonal TCR repertoire, we observe a decrease in positive selection. This reduction in positive selection was also observed when ERK3-deficient mice were backcrossed to class I- and class II-restricted TCR transgenic mice. Furthermore, the response of DP thymocytes to in vitro TCR stimulation was strongly reduced in ERK3-deficient mice. Together, these results show that ERK3 expression following TCR signalling is critical for proper thymic positive selection.
authors.affiliation: Maisonneuve-Rosemont Hospital Research Centre, Montreal, QC, Canada; Department of Microbiology, Infection and Immunology, University of Montreal, Montreal, QC, Canada.
authors.forename: Julien
authors.initials: J
authors.lastname: Sirois
authors.forename: Jean-François
authors.initials: JF
authors.lastname: Daudelin
authors.forename: Salix
authors.initials: S
authors.lastname: Boulet
authors.forename: Miriam
authors.initials: M
authors.lastname: Marquis
authors.forename: Sylvain
authors.initials: S
authors.lastname: Meloche
authors.forename: Nathalie
authors.initials: N
authors.lastname: Labrecque
mesh_terms: D000818:Animals; D060966:Clonal Selection, Antigen-Mediated; D015971:Gene Expression Regulation, Enzymologic / Q000235:genetics / Q000276:immunology; D020935:MAP Kinase Signaling System / Q000235:genetics / Q000276:immunology*; D051379:Mice; D018345:Mice, Knockout; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000276:immunology; D048053:Mitogen-Activated Protein Kinase 6 / Q000235:genetics / Q000276:immunology*; D011948:Receptors, Antigen, T-Cell / Q000235:genetics / Q000276:immunology*; D013601:T-Lymphocytes / Q000166:cytology / Q000276:immunology*; D060168:Thymocytes / Q000166:cytology / Q000276:immunology*; D013950:Thymus Gland / Q000166:cytology / Q000276:immunology*
chemical_list: D011948:Receptors, Antigen, T-Cell; C474633:Mapk6 protein, mouse; D048052:Mitogen-Activated Protein Kinase 3; D048053:Mitogen-Activated Protein Kinase 6
keywords: mitogen-activated protein kinases; positive selection; thymus