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 language | English (US) |
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Pages (from-to) | 5871-5877 |
Number of pages | 7 |
Journal | The EMBO journal |
Volume | 13 |
Issue number | 24 |
State | Published - 1994 |
Externally published | Yes |
Keywords
- β-PTyr
- IFNAR chain
- Type I interferon receptor
- Tyrosine phosphorylation
ASJC Scopus subject areas
- Cell Biology
- Genetics