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dc.contributor.authorLawson, VJen_US
dc.contributor.authorWeston, Ken_US
dc.contributor.authorMaurice, Den_US
dc.date.accessioned2018-08-24T08:25:41Z
dc.date.issued2010-01en_US
dc.identifier1en_US
dc.identifier.citationEUROPEAN JOURNAL OF IMMUNOLOGY, 2010, 40 pp. 232 - 241en_US
dc.identifier.issn0014-2980en_US
dc.identifier.urihttps://repository.icr.ac.uk/handle/internal/2379
dc.identifier.doi10.1002/eji.200939567en_US
dc.description.abstractThe early growth response (Egr) transcription factor family regulates multiple steps during T-cell development. We examine here the role played by Egr2 in positive selection. in double-positive cells, Egr2 is upregulated immediately following TCR ligation, and its expression requires both the MAPK and calcineurin signaling pathways. Inducible transgenic and knockout mice were generated to cause gain- or loss-of-function of Egr2 in double-positive cells, and had reciprocal effects; more mature single-positive cells were made when Egr2 was overexpressed, and fewer when Egr2 was absent. These defects were associated with changes in the survival of positively selected cells rather than perturbation of positive selection or immediate post-selection signaling. The survival function of Egr2 at least partly depends upon its ability to activate the cytokine-mediated survival pathway, likely through negative regulation of both the IL-7R and suppressor of cytokine signaling 1 (Socs1), the molecular switch whose downregulation normally results in restored responsiveness to cytokine signaling following selection. While gain of Egr2 caused a decrease in Socs1 mRNA, loss of Egr2 resulted in downregulation of IL-7R, upregulation of Socs1, and inhibition of Stat5 phosphorylation and IL-7-mediated survival post-selection. Therefore, expression of Egr2 following positive selection links the initial TCR signaling event to subsequent survival of signaled cells.en_US
dc.format.extent232 - 241en_US
dc.languageEnglishen_US
dc.language.isoEnglishen_US
dc.publisherWILEY-V C H VERLAG GMBHen_US
dc.titleEarly growth response 2 regulates the survival of thymocytes during positive selectionen_US
dc.typeJournal Article
rioxxterms.versionofrecord10.1002/eji.200939567en_US
rioxxterms.licenseref.startdate2010-01en_US
rioxxterms.typeJournal Article/Reviewen_US
dc.relation.isPartOfEUROPEAN JOURNAL OF IMMUNOLOGYen_US
pubs.notesaffiliation: Weston, K (Reprint Author), Inst Canc Res, Sect Cell & Mol Biol, 237 Fulham Rd, London SW3 6JB, England. Lawson, Victoria J.; Weston, Kathleen; Maurice, Diane, Inst Canc Res, Sect Cell & Mol Biol, London SW3 6JB, England. keywords: Bcl2; Egr2; Positive selection; Suppressor of cytokine signaling 1; T-cell keywords-plus: T-CELL DEVELOPMENT; PRE-TCR SIGNALS; TRANSCRIPTION FACTORS; NEGATIVE SELECTION; LINEAGE COMMITMENT; TRANSGENIC MICE; CYTOKINE SIGNALING-1; THYMIC SELECTION; BETA-SELECTION; GENE INDUCTION research-areas: Immunology web-of-science-categories: Immunology author-email: kathy.weston@icr.ac.uk funding-acknowledgement: Cancer Research UK; Institute of Cancer Research funding-text: This work was supported by Cancer Research UK and the Institute of Cancer Research. The authors thank Fredrik Wallberg, Derek Davies, Demelza Bird, Mathew Sargent and Vladimir Grigoriev for technical assistance, and Patrick Costello and Richard Treisman for helpful discussions. number-of-cited-references: 47 times-cited: 17 usage-count-last-180-days: 0 usage-count-since-2013: 3 journal-iso: Eur. J. Immunol. doc-delivery-number: 549IP unique-id: ISI:000274041800026 oa: gold_or_bronze da: 2018-08-23en_US
pubs.notesNot knownen_US
pubs.organisational-group/ICR
pubs.volume40en_US
pubs.embargo.termsNot knownen_US
dc.contributor.icrauthorMaurice, Dianeen_US
dc.contributor.icrauthorWeston, Kathleenen_US
dc.contributor.icrauthorLawson, Victoriaen_US


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