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dc.contributor.authorKovanen, Panu E.
dc.contributor.authorBernard, Jerome
dc.contributor.authorAl-Shami, Amin
dc.contributor.authorLiu, Chengyu
dc.contributor.authorBollenbacher-Reilley, Julie
dc.contributor.authorYoung, Lynn
dc.contributor.authorPise-Masison, Cynthia Ann
dc.contributor.authorSpolski, Rosanne
dc.contributor.authorLeonard, Warren J.
dc.date2022-08-11T08:08:52.000
dc.date.accessioned2022-08-23T16:10:27Z
dc.date.available2022-08-23T16:10:27Z
dc.date.issued2008-04-24
dc.date.submitted2009-02-24
dc.identifier.citationJ Biol Chem. 2008 Jun 20;283(25):17362-9. Epub 2008 Apr 21. <a href="http://dx.doi.org/10.1074/jbc.M709887200">Link to article on publisher's site</a>
dc.identifier.issn0021-9258 (Print)
dc.identifier.doi10.1074/jbc.M709887200
dc.identifier.pmid18430737
dc.identifier.urihttp://hdl.handle.net/20.500.14038/32937
dc.description.abstractInterleukin-2 (IL-2) is a pleiotropic cytokine that regulates lymphocyte proliferation and peripheral tolerance. IL-2 activates mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase, and signal transducer and activator of transcription (STAT) pathways and modulates expression of target genes. Systematic analysis of IL-2 target genes has revealed regulation of potential feedback inhibitors of IL-2 signaling, including several suppressor of cytokine signaling (SOCS) family members as well as MAPK pathway-regulating dual specificity phosphatases (DUSPs). Here we have evaluated the in vivo actions of DUSP5, an extracellular signal-regulated kinase 1/2 (ERK1/2)-specific phosphatase, by generating transgenic mice overexpressing DUSP5 within the lymphoid compartment. We show that transgenic DUSP5 expression results in a block in thymocyte development at the double positive stage. We also demonstrate that DUSP5-expressing mature T cells exhibit decreased IL-2-dependent proliferation and defective IL-2-mediated induction of genes. Finally, DUSP5 transgenic mice develop autoimmune symptoms, suggesting a role for the MAPK pathway in the regulation of tolerance. Thus, proper regulation of DUSP5 activity is critical for normal immune system development, IL-2 actions, and tolerance.
dc.language.isoen_US
dc.relation<a href="http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed&cmd=Retrieve&list_uids=18430737&dopt=Abstract">Link to Article in PubMed</a>
dc.relation.urlhttp://dx.doi.org/10.1074/jbc.M709887200
dc.subject1-Phosphatidylinositol 3-Kinase; Animals; Dual-Specificity Phosphatases; Humans; Immune Tolerance; Interleukin-2; MAP Kinase Signaling System; Mice; Mice, Inbred C57BL; Mice, Transgenic; Mitogen-Activated Protein Kinase 1; Mitogen-Activated Protein Kinase 3; Models, Biological; T-Lymphocytes; Thymus Gland
dc.subjectLife Sciences
dc.subjectMedicine and Health Sciences
dc.titleT-cell development and function are modulated by dual specificity phosphatase DUSP5
dc.typeJournal Article
dc.source.journaltitleThe Journal of biological chemistry
dc.source.volume283
dc.source.issue25
dc.identifier.legacycoverpagehttps://escholarship.umassmed.edu/gsbs_sp/1489
dc.identifier.contextkey738054
html.description.abstract<p>Interleukin-2 (IL-2) is a pleiotropic cytokine that regulates lymphocyte proliferation and peripheral tolerance. IL-2 activates mitogen-activated protein kinase (MAPK), phosphatidylinositol 3-kinase, and signal transducer and activator of transcription (STAT) pathways and modulates expression of target genes. Systematic analysis of IL-2 target genes has revealed regulation of potential feedback inhibitors of IL-2 signaling, including several suppressor of cytokine signaling (SOCS) family members as well as MAPK pathway-regulating dual specificity phosphatases (DUSPs). Here we have evaluated the in vivo actions of DUSP5, an extracellular signal-regulated kinase 1/2 (ERK1/2)-specific phosphatase, by generating transgenic mice overexpressing DUSP5 within the lymphoid compartment. We show that transgenic DUSP5 expression results in a block in thymocyte development at the double positive stage. We also demonstrate that DUSP5-expressing mature T cells exhibit decreased IL-2-dependent proliferation and defective IL-2-mediated induction of genes. Finally, DUSP5 transgenic mice develop autoimmune symptoms, suggesting a role for the MAPK pathway in the regulation of tolerance. Thus, proper regulation of DUSP5 activity is critical for normal immune system development, IL-2 actions, and tolerance.</p>
dc.identifier.submissionpathgsbs_sp/1489
dc.contributor.departmentLaboratory of Molecular Immunology
dc.contributor.departmentGraduate School of Biomedical Sciences
dc.source.pages17362-9


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