HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

J. Biol. Chem., Vol. 281, Issue 18, 12587-12595, May 5, 2006

This Article Full Text Full Text (PDF) All Versions of this Article: 281/18/12587    most recent M600497200v1 Submit a Letter to Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Mao, J. Articles by Wu, J. Search for Related Content PubMed PubMed Citation Articles by Mao, J. Articles by Wu, J. Social Bookmarking                      What's this?

Transgenic Drak2 Overexpression in Mice Leads to Increased T Cell Apoptosis and Compromised Memory T Cell Development^*

Jianning Mao¹, Xiaoying Qiao¹, Hongyu Luo², and Jiangping Wu, National Scholar of the Fonds de la Recherche en Santé du Québec³

From the Laboratory of Immunology and Nephrology Service, Centre Hospitalier de l'Université de Montréal, Notre Dame Hospital, Montreal, Quebec H2L 4M1, Canada

Drak2 is a death-associated protein family serine-threonine kinase. Its expression and roles in the immune system were investigated in this study. According to in situ hybridization, Drak2 expression was ubiquitous at the mid-gestation stage in embryos, followed by more focal expression in various organs in the perinatal period and adulthood, notably in the thymus, spleen, lymph nodes, cerebellum, suprachiasmatic nuclei, pituitary, olfactory lobes, adrenal medulla, stomach, skin, and testes. Drak2 transgenic (Tg) mice were generated using the human -actin promoter. These Tg mice showed normal T cell versus B cell and CD4 versus CD8 populations in the spleen, but their spleen weight cellularity was lower in comparison with wild type mice. After TCR activation, the proliferation response in Drak2 Tg T cells was normal, although their interleukin (IL)-2 and IL-4 but not interferon- production was augmented. Activated Drak2 Tg T cells demonstrated significantly enhanced apoptosis in the presence of exogenous IL-2. At the molecular level, Drak2 Tg T cells manifested a lower increase of anti-apoptotic factors during activation; such a change probably rendered the cells vulnerable to subsequent IL-2 insults. The compromised apoptosis in Drak2 Tg T cells was associated with reduced numbers of T cells with the memory cell phenotype (CD62L^lo) and repressed secondary T cell responses in delayed type hypersensitivity. Our study demonstrates that Drak2 expresses in the T cell compartment but is not T cell-specific; it plays critical roles in T cell apoptosis and memory T cell development.

Received for publication, January 17, 2006 , and in revised form, February 24, 2006.

^* This work was supported by Canadian Institutes of Health Research Grants MOP57697 and MOP69089 and funds from the Kidney Foundation of Canada, funds from the Heart and Stroke Foundation of Quebec, Juvenile Diabetes Research Foundation USA Grant 1-2005-197, and funds from the J.-Louis Levesque Foundation (to J. W.). This work was also supported by group grants from the Canadian Institutes of Health Research for New Emerging Teams in Transplantation and from Fonds de la Recherche en Santé du Québec for Transfusional and Hemovigilance Medical Research. 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 These authors contributed equally to this work.

² To whom correspondence may be addressed: Laboratory of Immunology, Research Centre, CHUM, Notre Dame Hospital, Pavilion DeSève, Rm. Y-5616, 1560 Sherbrooke St. East, Montreal, PQ H2L 4M1, Canada. Tel.: 514-890-8000 (ext. 27421); Fax: 514-412-7596; E-mail: hongyu.luo{at}umontreal.ca. ³ To whom correspondence may be addressed: Laboratory of Immunology, Research Centre, CHUM, Notre Dame Hospital, Pavilion DeSève, Rm. Y-5616, 1560 Sherbrooke St. East, Montreal, PQ H2L 4M1, Canada. Tel.: 514-890-8000 (ext. 25164); Fax: 514-412-7596; E-mail: jianping.wu{at}umontreal.ca.

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this?

This article has been cited by other articles:

				M. Gatzka, R. H. Newton, and C. M. Walsh Altered Thymic Selection and Increased Autoimmunity Caused by Ectopic Expression of DRAK2 during T Cell Development J. Immunol., July 1, 2009; 183(1): 285 - 297. [Abstract] [Full Text] [PDF]

				J. Mao, H. Luo, B. Han, R. Bertrand, and J. Wu Drak2 Is Upstream of p70S6 Kinase: Its Implication in Cytokine-Induced Islet Apoptosis, Diabetes, and Islet Transplantation J. Immunol., April 15, 2009; 182(8): 4762 - 4770. [Abstract] [Full Text] [PDF]

				M. A. McGargill, C. Choy, B. G. Wen, and S. M. Hedrick Drak2 Regulates the Survival of Activated T Cells and Is Required for Organ-Specific Autoimmune Disease J. Immunol., December 1, 2008; 181(11): 7593 - 7605. [Abstract] [Full Text] [PDF]

				S. J. Ramos, J. B. Hernandez, M. Gatzka, and C. M. Walsh Enhanced T Cell Apoptosis within Drak2-Deficient Mice Promotes Resistance to Autoimmunity J. Immunol., December 1, 2008; 181(11): 7606 - 7616. [Abstract] [Full Text] [PDF]

				D. A. Dalmas, M. S. Scicchitano, Y. Chen, J. Kane, R. Mirabile, L. W. Schwartz, H. C. Thomas, and R. W. Boyce Transcriptional Profiling of Laser Capture Microdissected Rat Arterial Elements: Fenoldopam-induced Vascular Toxicity as a Model System Toxicol Pathol, April 1, 2008; 36(3): 496 - 519. [Abstract] [Full Text] [PDF]

				Y.-T. Chuang, L.-W. Fang, M.-H. Lin-Feng, R.-H. Chen, and M.-Z. Lai The Tumor Suppressor Death-Associated Protein Kinase Targets to TCR-Stimulated NF-{kappa}B Activation J. Immunol., March 1, 2008; 180(5): 3238 - 3249. [Abstract] [Full Text] [PDF]

				H. Kuwahara, M. Nishizaki, and H. Kanazawa Nuclear Localization Signal and Phosphorylation of Serine350 Specify Intracellular Localization of DRAK2 J. Biochem., March 1, 2008; 143(3): 349 - 358. [Abstract] [Full Text] [PDF]