T-cell development and function are modulated by dual specificity phosphatase DUSP5
Authors
Kovanen, Panu E.Bernard, Jerome
Al-Shami, Amin
Liu, Chengyu
Bollenbacher-Reilley, Julie
Young, Lynn
Pise-Masison, Cynthia Ann
Spolski, Rosanne
Leonard, Warren J.
Document Type
Journal ArticlePublication Date
2008-04-24Keywords
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 GlandLife Sciences
Medicine and Health Sciences
Metadata
Show full item recordAbstract
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.Source
J Biol Chem. 2008 Jun 20;283(25):17362-9. Epub 2008 Apr 21. Link to article on publisher's siteDOI
10.1074/jbc.M709887200Permanent Link to this Item
http://hdl.handle.net/20.500.14038/32937PubMed ID
18430737Related Resources
Link to Article in PubMedae974a485f413a2113503eed53cd6c53
10.1074/jbc.M709887200