Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon receptor and of an associated surface protein in response to IFN-α and IFN-β

C. Abramovich, L. M. Shulman, E. Ratovitski, S. Harroch, M. Tovey, P. Eid, M. Revel

Research output: Contribution to journalArticle

Abstract

The human interferon α-receptor (IFNAR gene product) is a transmembranal protein of 557 amino acids with an intracytoplasmic domain of 100 amino acids containing four tyrosines. Antibodies to a C-terminal peptide (residues 521-536) were developed which efficiently immunoprecipitate the 105 kDa IFNAR protein from detergent extracts of human cells. We show that the IFNAR protein becomes tyrosine phosphorylated within 5 min after treatment of human myeloma U266 cells with IFN-α2, IFN-α8 or IFN-β. The IFNAR chain interacts with both IFN-α2 and IFN-β, as demonstrated by cross-linking. Among elements involved in signal transduction by type I IFNs, the tyrosine kinase Tyk2 but not Jak1, and the ISGF3 transcription factor subunit Stat2 (p113) but not Stat1 (p91), are found associated with the IFNAR protein. After IFN-β treatment for 5 min, a tyrosine-phosphorylated protein of -95 kDa (β-PTyr) is found bound to IFNAR, but can be dissociated by denaturation. The β-PTyr protein is present on the cell surface, like IFNAR, as shown by extracellular biotin tagging. The ratio of β-PTyr to IFNAR tyrosine phosphorylation is much higher with IFN-β than with IFN-α2 or 8. Both are IFN dependent and abrogated by a monoclonal antibody which blocks IFNAR action. The β-PTyr component may represent an important difference in the action of IFN-β as compared with IFN-α in their shared receptor system.

Original languageEnglish (US)
Pages (from-to)5871-5877
Number of pages7
JournalThe EMBO journal
Volume13
Issue number24
StatePublished - 1994
Externally publishedYes

Fingerprint

Interferon alpha-beta Receptor
Phosphorylation
Tyrosine
Membrane Proteins
Proteins
Interferon-Stimulated Gene Factor 3
Interferon Receptors
Amino Acids
Signal transduction
Denaturation
Biotin
Cell Extracts
Detergents
Protein-Tyrosine Kinases
Signal Transduction
Genes
Monoclonal Antibodies
Cells
Peptides
Antibodies

Keywords

  • β-PTyr
  • IFNAR chain
  • Type I interferon receptor
  • Tyrosine phosphorylation

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

Cite this

Abramovich, C., Shulman, L. M., Ratovitski, E., Harroch, S., Tovey, M., Eid, P., & Revel, M. (1994). Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon receptor and of an associated surface protein in response to IFN-α and IFN-β. The EMBO journal, 13(24), 5871-5877.

Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon receptor and of an associated surface protein in response to IFN-α and IFN-β. / Abramovich, C.; Shulman, L. M.; Ratovitski, E.; Harroch, S.; Tovey, M.; Eid, P.; Revel, M.

In: The EMBO journal, Vol. 13, No. 24, 1994, p. 5871-5877.

Research output: Contribution to journalArticle

Abramovich, C, Shulman, LM, Ratovitski, E, Harroch, S, Tovey, M, Eid, P & Revel, M 1994, 'Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon receptor and of an associated surface protein in response to IFN-α and IFN-β', The EMBO journal, vol. 13, no. 24, pp. 5871-5877.
Abramovich, C. ; Shulman, L. M. ; Ratovitski, E. ; Harroch, S. ; Tovey, M. ; Eid, P. ; Revel, M. / Differential tyrosine phosphorylation of the IFNAR chain of the type I interferon receptor and of an associated surface protein in response to IFN-α and IFN-β. In: The EMBO journal. 1994 ; Vol. 13, No. 24. pp. 5871-5877.
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