CLONING AND CHARACTERIZATION OF SOLUBLE AND TRANSMEMBRANE ISOFORMS OFA NOVEL COMPONENT OF THE MURINE TYPE-I INTERFERON RECEPTOR, IFNAR-2

This report describes the cloning of cDNAs encoding transmembrane and soluble isoforms of a novel chain of the murine type I interferon (IFN ) receptor and characterization of its capability to bind ligand and t ransduce signals, The transmembrane receptor (murine IFNAR 2c) has an extracellular domain of 215 amino acids and an intracellular domain of 250 amino acids, with 48% amino acid and 71% nucleotide identity with human IFNAR 2c, The cDNA for the soluble murine receptor (IFNAR 2a) e ncodes a 221-amino acid polypeptide identical to the first 210 amino a cids of IFNAR 2c plus a novel 11 amino acids, Northern blot analyses s how that murine IFNAR 2 is expressed as two transcripts of 4 kilobases encoding the transmembrane isoform and 1.5 kilobases encoding the mor e abundant soluble isoform, Studies using primary murine cells that la ck IFNAR 1 show that IFNAR 2 is expressed, and cells bind type I IFN l igand, but do not transduce signals as detected by electrophoretic mob ility shift assays of ISGF3 or GAF complexes binding to their cognate oligonucleotides, These cells show no effects on the ability of IFN ga mma to activate these complexes, These studies demonstrate that the IF NAR 2 transmembrane (2c) and soluble (2a) isoforms are conserved betwe en the human and mouse and that IFNAR 2c has intrinsic ligand binding activity, but no intrinsic signal transducing activity as measured in this study.