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, inc luding T lymphocytes. Fas ligand (Fast), a 40-kD type II membrane protein a lso expressed in activated T cells, belongs to the tumor necrosis factor li gand family. We describe a new alternative splicing of mouse Fast, named Fa st 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 75 6 and preserves the same reading frame as Fast, resulting in a short molecu le lacking the intracellular, the transmembrane, and part of the extracellu lar domains. RNase protection and immunoprecipitation analysis showed that Fasts is expressed in nonactivated normal spleen cells and in hybridoma T c ells and that it is upregulated upon activation by anti-CD3 monoclonal anti body (MoAb). Moreover, FasLs-transfected cells expressed soluble Fasts in t he supernatant and became resistant to apoptosis induced by agonist anti-Fa s 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 Socie ty of Hematology.