Transmembrane Signaling by the Subunit of the Type I Interferon Receptor Is Essential for Activation of the Jak Kinases and the Transcriptional Factor ISGF3

• Published in: The Journal of biological chemistry 1995-04, Vol.270 (14), p.8188
• Main Authors: Oscar R. Colamonici, Leonidas C. Platanias, Paul Domanski, Raj Handa, Kimberly C. Gilmour, Manuel O. Diaz, Nancy Reich, Paula Pitha-Rowe
• Format: Article
• Language: English
• ISSN: 0021-9258; 1083-351X
• DOI: 10.1074/jbc.270.14.8188

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 α subunit in mouse L-929 cells confers antiviral response to human IFNα8, but not to human IFNα2 or IFNβ. This antiviral 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 antiviral 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 α subunit are able to tyrosine-phosphorylate p135 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.