The human interferon alpha/beta receptor: characterization and molecular cloning.
We describe a universal ligand-binding receptor for human interferons alpha and interferon beta (type I IFNs). A soluble 40 kDa IFN-alpha/beta receptor (p40) that blocks the activity of type I IFNs was purified from urine and sequenced. Antibodies raised against p40 completely block the activity of several type I IFNs and immuno-precipitate both a cellular 102 kDa IFN-alpha/beta receptor and its cross-linked complexes with IFN-alpha 2. The receptor is a disulfide-linked dimer, consisting of 51 kDa subunits. We isolated and expressed a 1.5 kb cDNA, coding for the IFN-alpha/beta receptor. Its 331 amino acid sequence includes a leader and a transmembrane region, while its ectodomain corresponds to p40. IFN-alpha/beta receptor is physically associated with the cytoplasmic Tyr kinase JAK1, hence, in addition to ligand binding, it is directly involved in signal transduction.
Novick
D
D
Department of Molecular Genetics and Virology Weizmann Institute of Science, Rehovot, Israel.
Cohen
B
B
Rubinstein
M
M
D016475:3T3 Cells; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000032:analysis; D000818:Animals; D000906:Antibodies; D001483:Base Sequence; D002462:Cell Membrane / Q000737:chemistry; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000032:analysis; D006801:Humans; D007370:Interferon Type I / Q000378:metabolism*; D008565:Membrane Proteins; D051379:Mice; D008969:Molecular Sequence Data; D009500:Neutralization Tests; D011505:Protein-Tyrosine Kinases / Q000032:analysis; D011817:Rabbits; D011869:Radioligand Assay; D053633:Receptor, Interferon alpha-beta; D017471:Receptors, Interferon / Q000032:analysis / Q000737:chemistry / Q000235:genetics* / Q000276:immunology / Q000302:isolation & purification / Q000378:metabolism*; D017421:Sequence Analysis; D017422:Sequence Analysis, DNA
D000596:Amino Acids; D000906:Antibodies; D018076:DNA, Complementary; D007370:Interferon Type I; D008565:Membrane Proteins; D017471:Receptors, Interferon; D053633:Receptor, Interferon alpha-beta; D011505:Protein-Tyrosine Kinases