Downregulation of Fas ligand by shedding.
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.
Tanaka
M
M
Department of Genetics, Osaka University Medical School, Suita, Japan.
Itai
T
T
Adachi
M
M
Nagata
S
S
D000818:Animals; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D053222:Fas Ligand Protein; D006801:Humans; D019169:Jurkat Cells; D008562:Membrane Glycoproteins / Q000096:biosynthesis* / Q000302:isolation & purification / Q000378:metabolism; D008666:Metalloendopeptidases / Q000378:metabolism; D051379:Mice; D016297:Mutagenesis, Site-Directed; D017354:Point Mutation; D011994:Recombinant Proteins / Q000096:biosynthesis / Q000302:isolation & purification / Q000378:metabolism; D017384:Sequence Deletion; D013601:T-Lymphocytes / Q000276:immunology; D014162:Transfection
C505661:FASLG protein, human; D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D011994:Recombinant Proteins; D008666:Metalloendopeptidases