The Journal of Experimental Medicine
Track the topics, authors and articles important to you
  Home | Help | Feedback | Subscriptions | Archive | Search | Table of Contents
Published online 20 March 2000.
This Article
Right arrow Full Text
Right arrow Full Text (PDF)
Right arrow Alert me when this article is cited
Right arrow Citation Map
Services
Right arrow Email this article
Right arrow Similar articles in this journal
Right arrow Similar articles in PubMed
Right arrow Alert me to new content in the JEM
Right arrow Download to citation manager
Citing Articles
Right arrow Citing Articles via HighWire
Right arrow Citing Articles via CrossRef
Right arrow Citing Articles via Google Scholar
Google Scholar
Right arrow Articles by Zhang, J.
Right arrow Articles by Delovitch, T. L.
Right arrow Search for Related Content
PubMed
Right arrow PubMed Citation
Right arrow Articles by Zhang, J.
Right arrow Articles by Delovitch, T. L.
Social Bookmarking
Add to CiteULike   Add to Complore   Add to Connotea   Add to Del.icio.us   Add to Digg   Add to Reddit   Add to Technorati  
What's this?
© The Rockefeller University Press, 0022-1007/2000/3/1017/ $5.00
The Journal of Experimental Medicine, Volume 191, Number 6, March 20, 2000 1017-1030

Original Article

Regulation of Fas Ligand Expression during Activation-induced Cell Death in T Cells by p38 Mitogen-activated Protein Kinase and c-Jun NH2-terminal Kinase

Jian Zhanga, Jian-Xin Gaoa, Kostantin Salojina, Qing Shaod, Marsha Grattana, Craig Meaghera,b, Dale W. Lairdd, and Terry L. Delovitcha,b,c
a Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, Ontario N6G 2V4, Canada
b Department of Microbiology and Immunology, University of Western Ontario, London, Ontario N6A 5C1, Canada
c Department of Medicine, University of Western Ontario, London, Ontario N6A 5C1, Canada
d Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario N6A 5C1, Canada

Correspondence to: Terry L. Delovitch, Director, Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, 1400 Western Rd., London, Ontario N6G 2V4, Canada. Tel:519-663-3972 Fax:519-663-3847 E-mail:del{at}rri.on.ca.

Released online: 20 March 2000

Activation-induced cell death (AICD) is a mechanism of peripheral T cell tolerance that depends upon an interaction between Fas and Fas ligand (FasL). Although c-Jun NH2-terminal kinase (JNK) and p38 mitogen-activated protein kinase (MAPK) may be involved in apoptosis in various cell types, the mode of regulation of FasL expression during AICD in T cells by these two MAPKs is incompletely understood. To investigate the regulatory roles of these two MAPKs, we analyzed the kinetics of TCR-induced p38 MAPK and JNK activity and their regulation of FasL expression and AICD. We report that both JNK and p38 MAPK regulate AICD in T cells. Our data suggest a novel model of T cell AICD in which p38 MAPK acts early to initiate FasL expression and the Fas-mediated activation of caspases. Subsequently, caspases stimulate JNK to further upregulate FasL expression. Thus, p38 MAPK and downstream JNK converge to regulate FasL expression at different times after T cell receptor stimulation to elicit maximum AICD.

Key Words: Fas ligand, apoptosis, p38 MAPK, JNK, T cells


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


This article has been cited by other articles:



  Home | Help | Feedback | Subscriptions | Archive | Search
TABLE OF CONTENTS