Interferon α (IFNα) signaling in cells expressing the variant form of the type I IFN receptor

Oscar R. Colamonici, Paul Domanski, John J. Krolewski, Xin Yuang Fu, Nancy C. Reich, Lawrence M. Pfeffer, Michelle E. Sweet, Leonidas C. Platanias

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Abstract

Two different Type I interferon receptors (IFN-R) have been described: the normal and the variant receptors. The α subunit of the Type I IFN-R has a molecular mass of 110 kDa in cells expressing normal and variant receptors. The β subunit has a molecular mass of approximately 100 kDa in cells that express normal receptors and 55 kDa in cells expressing the variant form of the receptor. The IFNα-resistant U-937 cell line expresses variant receptors and fails to down-regulate and phosphorylate the α subunit on tyrosine residues. We report that two other myelomonocytic cell lines, YK-M2 and ML- 2, also expressing the variant form of the receptor, fail to down-regulate and phosphorylate the α subunit on tyrosine residues. However, YK-M2 and ML- 2 cells are sensitive to the antiproliferative and antiviral effects of IFNα2, indicating that phosphorylation of the α subunit is not necessary to elicit an IFNα response and that expression of variant receptors is not a source of IFNα resistance. We also determined if other proteins involved in the IFNα signal transduction pathway had a different phosphorylation pattern. Treatment of cells expressing variant receptors induced tyrosine phosphorylation of the p135(tyk2) tyrosine kinase, and the three interferon- stimulated gene factor 3α (ISGF3α) polypeptides (p113, p91, and p84), albeit at lower levels. These results indicate that cells expressing either form of the Type I IFN-R phosphorylate a similar set of proteins, with the exception of the α subunit.

Original languageEnglish (US)
Pages (from-to)5660-5665
Number of pages6
JournalJournal of Biological Chemistry
Volume269
Issue number8
StatePublished - Feb 25 1994

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ASJC Scopus subject areas

  • Biochemistry
  • Molecular Biology
  • Cell Biology

Cite this

Colamonici, O. R., Domanski, P., Krolewski, J. J., Fu, X. Y., Reich, N. C., Pfeffer, L. M., Sweet, M. E., & Platanias, L. C. (1994). Interferon α (IFNα) signaling in cells expressing the variant form of the type I IFN receptor. Journal of Biological Chemistry, 269(8), 5660-5665.