Cutting edge: Extracellular signal-related kinase is not required for negative selection of developing T cells.
Signals initiated through the TCR during development can result in either survival and differentiation or cell death. High affinity signals that induce death elicit a robust yet transient activation of signaling pathways, including Erk, whereas low affinity ligands, which promote survival, generate a gradual and weaker activation of the same pathways. It was recently demonstrated that Erk localizes to distinct cellular locations in response to high and low affinity ligands. Although a requirement for Erk in positive selection is well established, its role in negative selection is controversial and, thus, the importance of Erk relocalization during development is not understood. In this study, we examined the role of Erk in negative selection using mice that are genetically deficient in both Erk1 and Erk2 in T cells. Results from three different models reveal that thymocyte deletion remains intact in the absence of Erk.
Molecular Biology Section, Division of Biological Sciences, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093, USA.
Maureen A
MA
McGargill
Irene L
IL
Ch'en
Carol D
CD
Katayama
Gilles
G
Pagès
Jacques
J
Pouysségur
Stephen M
SM
Hedrick
D000818:Animals; D017637:Clonal Deletion; D051379:Mice; D018345:Mice, Knockout; D008822:Mice, Transgenic; D019950:Mitogen-Activated Protein Kinase 1 / Q000235:genetics / Q000502:physiology*; D048052:Mitogen-Activated Protein Kinase 3 / Q000235:genetics / Q000502:physiology*; D009924:Organ Culture Techniques; D013601:T-Lymphocytes / Q000201:enzymology / Q000276:immunology*; D013950:Thymus Gland / Q000201:enzymology / Q000276:immunology*
D019950:Mitogen-Activated Protein Kinase 1; D048052:Mitogen-Activated Protein Kinase 3