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

Keywords

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

ASJC Scopus subject areas

  • Cell Biology
  • Genetics

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    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.