A naturally occurring soluble isoform of murine Fas generated by alternative splicing.
We report a soluble isoform of mouse Fas, which is generated by alternative splicing of Fas mRNA to a newly identified exon located between exons 2 and 3 of the previously published Fas sequence. This splicing event creates a novel Fas transcript, Fas beta, with the potential to encode a truncated form of the extracellular domain, termed Fas B. In vitro, P815 mastocytoma cells transfected with Fas B become resistant to Fas ligand-induced apoptosis, and the resistance is mediated by a secreted product of the transfected cells. In vivo, Fas beta mRNA expression is correlated inversely with apoptosis among subsets of intrahepatic T lymphocytes, a cell population in which activation-induced T cell apoptosis occurs. We propose that Fas B is a new cytokine that acts physiologically to limit apoptosis induced by Fas ligand.
Hughes
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Immunobiology Section, Yale University Medical School, New Haven, Connecticut 06510, USA.
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D000595:Amino Acid Sequence; D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D001483:Base Sequence; D005091:Exons / Q000235:genetics; D053222:Fas Ligand Protein; D008099:Liver / Q000276:immunology; D008213:Lymphocyte Activation; D008232:Lymphoproliferative Disorders / Q000235:genetics; D012515:Mast-Cell Sarcoma / Q000473:pathology; D008562:Membrane Glycoproteins / Q000494:pharmacology; D051379:Mice; D008810:Mice, Inbred C57BL; D008969:Molecular Sequence Data; D012326:RNA Splicing; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D012995:Solubility; D014162:Transfection; D014407:Tumor Cells, Cultured; D019014:fas Receptor / Q000737:chemistry / Q000235:genetics*
D053222:Fas Ligand Protein; C505658:Fasl protein, mouse; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D011994:Recombinant Proteins; D019014:fas Receptor