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Cutting Edge: Extracellular Signal-Related Kinase Is Not Required for Negative Selection of Developing T Cells¹

Maureen A. McGargill,^2* Irene L. Ch'en,^* Carol D. Katayama,^* Gilles Pagès, Jacques Pouysségur, and Stephen M. Hedrick^3*

^*Molecular Biology Section, Division of Biological Sciences, Department of Cellular and Molecular Medicine, University of California San Diego, La Jolla, CA 92093; and University of Nice-Sophia Antipolis, Institute of Developmental Biology and Cancer Research, UMR Centre National de la Recherche Scientifique 6543, Centre Antoine Lacassagne, Nice, France

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.

The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked advertisement in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

¹ This work was supported by Public Health Service Grant 5R01 AI021372-26 (to S.M.H.) and by Juvenile Diabetes Research Foundation Grant 2-2007-105 (to M.A.M.).

² Current Address: St. Jude Children’s Research Hospital, Department of Immunology, Memphis, TN 38105.

³ Address correspondence and reprint requests to Dr. Stephen M. Hedrick, Molecular Biology Section, Room 5121, Natural Science Building, 9500 Gilman Drive, University of California San Diego, La Jolla, CA 92093-0377. E-mail address: shedrick{at}ucsd.edu

⁴ Abbreviations used in this paper: OVAp, OVA peptide; DKO, double knockout; DN, double negative; DP, double positive; FTOC, fetal thymic organ culture; RIP-mOVA, membrane-bound OVA under control of the rat insulin promoter; SP, single positive; WT, wild type.