Cloning and expression of a short Fas ligand: A new alternatively spliced product of the mouse Fas ligand gene

The Fas/FasL system mediates apoptosis in several different cell types, including T lymphocytes. Fas ligand (Fast), a 40-kD type II membrane protein also expressed in activated T cells, belongs to the tumor necrosis factor ligand family. We describe a new alternative splicing of mouse Fast, named Fast short (FasLs), cloned by reverse transcriptase-polymerase chain reaction. Fasts is encoded by part: of exon 1 and part of exon 4 of Fast gene. The protein encoded by Fasts mRNA has a putative initiation code at position 756 and preserves the same reading frame as Fast, resulting in a short molecule lacking the intracellular, the transmembrane, and part of the extracellular domains. RNase protection and immunoprecipitation analysis showed that Fasts is expressed in nonactivated normal spleen cells and in hybridoma T cells and that it is upregulated upon activation by anti-CD3 monoclonal antibody (MoAb). Moreover, FasLs-transfected cells expressed soluble Fasts in the supernatant and became resistant to apoptosis induced by agonist anti-Fas MoAb. Thus, Fasts, a new alternative splicing of Fast, is involved in the regulation of Fas/FasL-mediated cell death. (C) 1999 by The American Society of Hematology.