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

Research output: Contribution to journalArticle

15 Citations (Scopus)

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
Externally publishedYes

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Interferon alpha-beta Receptor
Interferons
Cells
Phosphorylation
Tyrosine
Interferon Type I
Molecular mass
Interferon-Stimulated Gene Factor 3
Down-Regulation
Cell Line
Signal transduction
Protein-Tyrosine Kinases
Antiviral Agents
Signal Transduction
Proteins
Peptides

ASJC Scopus subject areas

  • Biochemistry

Cite this

Colamonici, O. R., Domanski, P., Krolewski, J. J., Fu, X. Y., Reich, N. C., Pfeffer, L. M., ... 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.

Interferon α (IFNα) signaling in cells expressing the variant form of the type I IFN receptor. / Colamonici, Oscar R.; Domanski, Paul; Krolewski, John J.; Fu, Xin Yuang; Reich, Nancy C.; Pfeffer, Lawrence M.; Sweet, Michelle E.; Platanias, Leonidas C.

In: Journal of Biological Chemistry, Vol. 269, No. 8, 25.02.1994, p. 5660-5665.

Research output: Contribution to journalArticle

Colamonici, OR, Domanski, P, Krolewski, JJ, Fu, XY, Reich, NC, Pfeffer, LM, Sweet, ME & Platanias, LC 1994, 'Interferon α (IFNα) signaling in cells expressing the variant form of the type I IFN receptor', Journal of Biological Chemistry, vol. 269, no. 8, pp. 5660-5665.
Colamonici OR, Domanski P, Krolewski JJ, Fu XY, Reich NC, Pfeffer LM et al. Interferon α (IFNα) signaling in cells expressing the variant form of the type I IFN receptor. Journal of Biological Chemistry. 1994 Feb 25;269(8):5660-5665.
Colamonici, Oscar R. ; Domanski, Paul ; Krolewski, John J. ; Fu, Xin Yuang ; Reich, Nancy C. ; Pfeffer, Lawrence M. ; Sweet, Michelle E. ; Platanias, Leonidas C. / Interferon α (IFNα) signaling in cells expressing the variant form of the type I IFN receptor. In: Journal of Biological Chemistry. 1994 ; Vol. 269, No. 8. pp. 5660-5665.
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