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 Zhang; Jian-Xin Gao; Kostantin Salojin; Qing Shao; Marsha Grattan; Craig Meagher; Dale W Laird; Terry L Delovitch

doi:10.1084/jem.191.6.1017

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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

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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 Zhang, Jian-Xin Gao, Kostantin Salojin, Qing Shao, Marsha Grattan, Craig Meagher, Dale W Laird and Terry L Delovitch

The Journal of experimental medicine, Vol.191(6), pp.1017-1030

03/20/2000

DOI: 10.1084/jem.191.6.1017

PMCID: PMC2193110

PMID: 10727463

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Abstract

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.

Details

Title: Subtitle: 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
Creators: Jian Zhang - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, Ontario N6G 2V4, Canada
Jian-Xin Gao - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, Ontario N6G 2V4, Canada
Kostantin Salojin - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, Ontario N6G 2V4, Canada
Qing Shao - Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario N6A 5C1, Canada
Marsha Grattan - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, Ontario N6G 2V4, Canada
Craig Meagher - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, Ontario N6G 2V4, Canada, Department of Microbiology and Immunology, University of Western Ontario, London, Ontario N6A 5C1, Canada
Dale W Laird - Department of Anatomy and Cell Biology, University of Western Ontario, London, Ontario N6A 5C1, Canada
Terry L Delovitch - Autoimmunity/Diabetes Group, The John P. Robarts Research Institute, London, Ontario N6G 2V4, Canada, Department of Microbiology and Immunology, University of Western Ontario, London, Ontario N6A 5C1, Canada, Department of Medicine, University of Western Ontario, London, Ontario N6A 5C1, Canada
Resource Type: Journal article
Publication Details: The Journal of experimental medicine, Vol.191(6), pp.1017-1030
DOI: 10.1084/jem.191.6.1017
PMID: 10727463
PMCID: PMC2193110
ISSN: 0022-1007
eISSN: 1540-9538
Language: English
Date published: 03/20/2000
Academic Unit: Pathology
Record Identifier: 9984046814302771

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