Cloning and characterization of soluble and transmembrane isoforms of a 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 transduce 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) encodes a 221-amino acid polypeptide identical to the first 210 amino acids of IFNAR 2c plus a novel 11 amino acids. Northern blot analyses show that murine IFNAR 2 is expressed as two transcripts of 4 kilobases encoding the transmembrane isoform and 1.5 kilobases encoding the more abundant soluble isoform. Studies using primary murine cells that lack IFNAR 1 show that IFNAR 2 is expressed, and cells bind type I IFN ligand, but do not transduce signals as detected by electrophoretic mobility shift assays of ISGF3 or GAF complexes binding to their cognate oligonucleotides. These cells show no effects on the ability of IFNgamma to activate these complexes. These studies demonstrate that the IFNAR 2 transmembrane (2c) and soluble (2a) isoforms are conserved between the human and mouse and that IFNAR 2c has intrinsic ligand binding activity, but no intrinsic signal transducing activity as measured in this study.
Owczarek
C M
CM
Molecular Genetics and Development Group, Institute of Reproduction and Development, Monash University, Clayton Victoria 3168, Australia.
Hwang
S Y
SY
Holland
K A
KA
Gulluyan
L M
LM
Tavaria
M
M
Weaver
B
B
Reich
N C
NC
Kola
I
I
Hertzog
P J
PJ
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D003001:Cloning, Molecular; D018076:DNA, Complementary; D006801:Humans; D008565:Membrane Proteins / Q000235:genetics*; D051379:Mice; D008969:Molecular Sequence Data; D011485:Protein Binding; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid; D015398:Signal Transduction; D012995:Solubility
D018076:DNA, Complementary; C507964:IFNAR1 protein, human; C508034:Ifnar2 protein, mouse; D008565:Membrane Proteins; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta