Downregulation of Fas ligand by shedding

Nat Med. 1998 Jan;4(1):31-6. doi: 10.1038/nm0198-031.


Apoptosis-inducing Fas ligand (FasL) is a type II membrane protein, predominantly expressed in the activated T cells. FasL is cleaved by a putative metalloproteinase to produce a soluble form. Here, we blocked the shedding of human FasL by deleting its cleavage site. Although human Jurkat cells and mouse primary hepatocytes that express a low level of Fas were resistant to the soluble form of FasL, they were efficiently killed by membrane-bound FasL. Furthermore, soluble FasL inhibited cytotoxicity of the membrane-bound FasL. These results indicate that the membrane-bound form of FasL is the functional form and suggest that shedding of FasL is to prevent the killing of the healthy bystander cells by cytotoxic T cells.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cytotoxicity, Immunologic
  • Fas Ligand Protein
  • Humans
  • Jurkat Cells
  • Membrane Glycoproteins / biosynthesis*
  • Membrane Glycoproteins / isolation & purification
  • Membrane Glycoproteins / metabolism
  • Metalloendopeptidases / metabolism
  • Mice
  • Mutagenesis, Site-Directed
  • Point Mutation
  • Recombinant Proteins / biosynthesis
  • Recombinant Proteins / isolation & purification
  • Recombinant Proteins / metabolism
  • Sequence Deletion
  • T-Lymphocytes / immunology
  • Transfection


  • FASLG protein, human
  • Fas Ligand Protein
  • Fasl protein, mouse
  • Membrane Glycoproteins
  • Recombinant Proteins
  • Metalloendopeptidases