Cell
Volume 77, Issue 3, 6 May 1994, Pages 391-400
Journal home page for Cell

Article
The human interferon αβ receptor: Characterization and molecular cloning

https://doi.org/10.1016/0092-8674(94)90154-6Get rights and content

Abstract

We describe a universal ligand-binding receptor for human interferons α and interferon β (type I IFNs). A soluble 40 kDa IFN-αβ 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 immunoprecipltate both a cellular 102 kDa IFN-αβ receptor and its cross-linked complexes with IFN-α2. 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-αβ receptor. Its 331 amino acid sequence includes a leader and a transmembrane region, while its ectodomain corresponds to p40. IFN-αβ receptor is physically associated with the cytoplasmic Tyr kinase JAK1, hence, in addition to ligand binding, it is directly involved in signal transduction.

References (49)

  • G. Lutfalla et al.

    A new member of the cytokine receptor family maps on chromosome 21 at less than 35 kb from IFNAR

    Genomics

    (1993)
  • P. Matsudaira

    Sequence from picomole quantities of proteins electroblotted onto polyvinylidene difluoride membranes

    J. Biol. Chem.

    (1987)
  • T. Miki et al.

    An efficient directional cloning system to construct cDNA libraries containing full-length inserts at high frequency

    Gene

    (1989)
  • D. Novick et al.

    The human interferon-γ receptor, purification, characterization and preparation of antibodies

    J. Biol. Chem.

    (1987)
  • D. Novick et al.

    Soluble interferonalpha receptor molecules are present in body fluids

    FEBS Lett.

    (1992)
  • B.R. Oakley et al.

    A simplified ultrasensitive silver stain for detecting proteins in polyacrylamide gels

    Anal. Biochem.

    (1980)
  • J. Soh et al.

    Identification and sequence of an accessory factor required for activation of the human interferon γ receptor

    Cell

    (1994)
  • N. Stahl et al.

    The alphas, betas, and kinases of cytokine receptor complexes

    Cell

    (1993)
  • T. Taniguchi et al.

    The nucleotide sequence of human fibroblast interferon cDNA

    Gene

    (1980)
  • A. Ullrich et al.

    Signal transduction by receptors with tyrosine kinase activity

    Cell

    (1990)
  • G. Uzé et al.

    Genetic transfer of a functional human interferon α receptor into mouse cells: cloning and expression of its cDNA

    Cell

    (1990)
  • B.A. Witthuhn et al.

    JAK2 associates with the erythropoietin receptor and is tyrosine phosphorylated and activated following stimulation with erythropoietin

    Cell

    (1993)
  • M. Aguet

    High affinity binding of 125I-labeled mouse interferon to a specific cell surface receptor

    Nature

    (1980)
  • P. Benoit et al.

    A monoclonal antibody to recombinant human IFN-alpha receptor inhibits biologic activity of several species of human IFN-alpha, IFN-beta, and IFN-omega

    Detection of heterogeneity of the cellular type I IFN receptor

    J. Immunol.

    (1993)
  • Cited by (615)

    View all citing articles on Scopus
    View full text