Transmembrane signaling by the α subunit of the type I interferon receptor is essential for activation of the Jak kinases and the transcriptional factor ISGF3

O. R. Colamonici*, L. C. Platanias, P. Domanski, R. Handa, K. C. Gilmour, M. O. Diaz, N. Reich, P. Pitha-Rowe

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

Abstract

The Type I interferon (IFN) receptor has a multisubunit structure. The component of the receptor that has been most thoroughly studied is the α subunit. Expression of the a subunit in mouse L-929 cells confers anti-vital response to human IFNα8, but not to human IFNα2 or IFNβ. This antivital effect is observed without a significant increase in IFN binding. It has not been determined why mouse cells expressing the human α subunit show different response to the antivital activity of distinct human Type I IFNs. In this report, we demonstrate that the response to human Type I IFNs in mouse cells expressing the α subunit is dependent on cross-binding to the mouse receptor. This is supported by the finding that human IFNα8, but not human IFNα2, cross-binds to the mouse receptor even in the absence of expression of the human α subunit. We also demonstrate that only mouse cells expressing the human a subunit are able to tyrosine-phosphorylate p135(tyk2) and JAK-1 and to form the ISGF3 complex in response to human IFNα8. These results demonstrate that the α subunit is essential for IFNα signaling through the JAK kinases and ISGF3.

Original languageEnglish (US)
Pages (from-to)8188-8193
Number of pages6
JournalJournal of Biological Chemistry
Volume270
Issue number14
DOIs
StatePublished - Apr 7 1995

ASJC Scopus subject areas

  • Molecular Biology
  • Biochemistry
  • Cell Biology

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