Document Detail

Polymorphism of murine Fas ligand that affects the biological activity.
MedLine Citation:
PMID:  9108079     Owner:  NLM     Status:  MEDLINE    
Fas ligand (FasL) is a member of the tumor necrosis factor family and induces apoptosis in Fas (CD95)-bearing target cells. In this study, we generated several mAbs that react with mouse FasL (mFasL) and characterized their functional properties. One of these mAbs, K10, specifically reacted with mFasL derived from C57BL/6 (B6) mice, but not that from BALB/c mice as estimated by surface staining and blocking of cytotoxic activities of mFasL transfectants, suggesting a polymorphism of mFasL. Sequence analysis of mFasL cDNA from several strains revealed that BALB/c and DBA/2 mice have three nucleotide differences from the known B6 and C3H sequences, which result in two amino acid substitutions (Thr-184 --> Ala-184 and Glu-218 --> Gly-218) in the extracellular region. Analysis of the K10 reactivity and genotyping by PCR-restriction fragment length polymorphism revealed that inbred mice segregate into the following two allotypes: mFasL.1 (B6, C3H, MRL, SJL, NOD, NZB, NZW) and mFasL.2 (BALB/c, DBA/1, DBA/2). Interestingly, COS7 cells expressing BALB/c FasL lysed Fas-bearing target cells more efficiently than those expressing B6 FasL. Furthermore, BALB/c-derived CD8-FasL fusion protein, which is composed of the extracellular domains of human CD8alpha and mFasL, exhibited 9-fold higher specific activity than did B6-derived CD8-FasL. These results suggest that in mFasL.2 mice the Fas/FasL system works more effectively than in mFasL.1 mice.
N Kayagaki; N Yamaguchi; F Nagao; S Matsuo; H Maeda; K Okumura; H Yagita
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Proceedings of the National Academy of Sciences of the United States of America     Volume:  94     ISSN:  0027-8424     ISO Abbreviation:  Proc. Natl. Acad. Sci. U.S.A.     Publication Date:  1997 Apr 
Date Detail:
Created Date:  1997-05-22     Completed Date:  1997-05-22     Revised Date:  2009-11-18    
Medline Journal Info:
Nlm Unique ID:  7505876     Medline TA:  Proc Natl Acad Sci U S A     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  3914-9     Citation Subset:  IM    
Department of Immunology, Juntendo University School of Medicine, Tokyo, Japan.
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MeSH Terms
Amino Acid Sequence
Fas Ligand Protein
Membrane Glycoproteins / genetics*,  metabolism
Molecular Sequence Data
Polymorphism, Genetic*
Structure-Activity Relationship
Reg. No./Substance:
0/FASLG protein, human; 0/Fas Ligand Protein; 0/Fasl protein, mouse; 0/Membrane Glycoproteins
Comment In:
Proc Natl Acad Sci U S A. 1997 Jun 10;94(12):5986-90   [PMID:  9177153 ]

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