T-cell development and function are modulated by dual specificity phosphatase DUSP5
dc.contributor.author | Kovanen, Panu E. | |
dc.contributor.author | Bernard, Jerome | |
dc.contributor.author | Al-Shami, Amin | |
dc.contributor.author | Liu, Chengyu | |
dc.contributor.author | Bollenbacher-Reilley, Julie | |
dc.contributor.author | Young, Lynn | |
dc.contributor.author | Pise-Masison, Cynthia Ann | |
dc.contributor.author | Spolski, Rosanne | |
dc.contributor.author | Leonard, Warren J. | |
dc.date | 2022-08-11T08:08:52.000 | |
dc.date.accessioned | 2022-08-23T16:10:27Z | |
dc.date.available | 2022-08-23T16:10:27Z | |
dc.date.issued | 2008-04-24 | |
dc.date.submitted | 2009-02-24 | |
dc.identifier.citation | J 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.issn | 0021-9258 (Print) | |
dc.identifier.doi | 10.1074/jbc.M709887200 | |
dc.identifier.pmid | 18430737 | |
dc.identifier.uri | http://hdl.handle.net/20.500.14038/32937 | |
dc.description.abstract | 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. | |
dc.language.iso | en_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.url | http://dx.doi.org/10.1074/jbc.M709887200 | |
dc.subject | 1-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.subject | Life Sciences | |
dc.subject | Medicine and Health Sciences | |
dc.title | T-cell development and function are modulated by dual specificity phosphatase DUSP5 | |
dc.type | Journal Article | |
dc.source.journaltitle | The Journal of biological chemistry | |
dc.source.volume | 283 | |
dc.source.issue | 25 | |
dc.identifier.legacycoverpage | https://escholarship.umassmed.edu/gsbs_sp/1489 | |
dc.identifier.contextkey | 738054 | |
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.submissionpath | gsbs_sp/1489 | |
dc.contributor.department | Laboratory of Molecular Immunology | |
dc.contributor.department | Graduate School of Biomedical Sciences | |
dc.source.pages | 17362-9 |