Document Detail

Qualitative and quantitative differences in the intensity of Fas-mediated intracellular signals determine life and death in T cells.
MedLine Citation:
PMID:  20658220     Owner:  NLM     Status:  MEDLINE    
Fas stimulation has been reported to promote the activation and proliferation of T lymphocytes, but the intracellular signalling pathways that mediate non-apoptotic responses to Fas are poorly defined. To distinguish between the activation signalling and the death-inducing pathway downstream of Fas, we generated a novel T cell line expressing a chimeric hCD8-FasC protein and found that stimulation with the anti-CD8 antibodies induced tyrosine phosphorylation of TCR-proximal proteins, activation of Raf-1/ERK, p38 and JNK, and increased expression of CD69, Fas, and Fas ligand. Stimulation of hCD8-FasC-induced activation of an atypical NF-kappaB pathway, partial cleavage of caspases, and increased expression of TRAF1, FLIP(L) and FLIP(S), thereby protecting T cells from FasL-mediated apoptosis. The proliferative response transmitted through hCD8-FasC chimeric receptors was converted into death signals when cells were stimulated, resulting in increased expression of IL-2 and Nur77 and increased caspase cleavage. Surprisingly, both the enhanced expression of FLIP(L) and FLIP(S) and the complete inhibition of FLIP(S) expression were functionally associated with cell death induction. These findings imply that Fas is able to trigger intracellular signalling events driving both apoptosis and activation of T cells but that cell fate is determined by quantitative and qualitative differences in intracellular signalling following Fas stimulation.
Min-Jung Shin; Jae-Hyuck Shim; Jae-Young Lee; Wook-Jin Chae; Heung-Kyu Lee; Tomohiro Morio; Jun Han Park; Eun-Ju Chang; Sang-Kyou Lee
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-24
Journal Detail:
Title:  International journal of hematology     Volume:  92     ISSN:  1865-3774     ISO Abbreviation:  Int. J. Hematol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-09     Completed Date:  2010-12-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9111627     Medline TA:  Int J Hematol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  262-70     Citation Subset:  IM    
Department of Biotechnology, College of Life Science and Biotechnology, Yonsei University, Seoul, Korea.
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MeSH Terms
Antigens, CD95 / immunology,  physiology*
Apoptosis / immunology*
Cell Line
Cell Proliferation
Lymphocyte Activation*
Protein Engineering
Recombinant Fusion Proteins
Signal Transduction / immunology*
T-Lymphocytes / cytology,  immunology*
Reg. No./Substance:
0/Antigens, CD95; 0/Recombinant Fusion Proteins

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