Interaction between the Components of the Interferon 
Receptor Complex (*)
- Serguei V. Kotenko,
- Lara S. Izotova,
- Brian P. Pollack,
- Thomas M. Mariano,
- Robert J. Donnelly,
- Geetha Muthukumaran,
- Jeffry R. Cook,
- Gianni Garotta(2),
- Olli Silvennoinen(3),
- James N. Ihle(3) and
- Sidney Pestka(1)
- From the (1)From theDepartment of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635,
- (2)Human Genome Sciences, Rockville, Maryland 20850-3338, and the
- (3)Department of Biochemistry, St. Jude Children's Hospital, Memphis, Tennessee 38105
Abstract
Interferon 
(IFN-
) signals through a multimeric receptor complex consisting of two different chains: the IFN-
receptor binding subunit (IFN-
R, IFN-
R1), and a transmembrane accessory factor (AF-1, IFN-
R2) necessary for signal transduction. Using cell lines expressing different cloned components of the IFN-
receptor complex, we examined the function of the receptor components in signal transduction upon IFN-
treatment. A specific IFN-
R2:IFN-
cross-linked complex was observed in cells expressing both IFN-
R1 and IFN-
R2 indicating that IFN-
R2 (AF-1) interacts with IFN-
and is closely associated with IFN-
R1. We show that the intracellular domain of IFN-
R2 is necessary for signaling. Cells coexpressing IFN-
R1 and truncated IFN-
R2, lacking the COOH-terminal 51 amino acids (residues 286-337), or cells expressing IFN-
R1 alone were unresponsive to IFN-
treatment as measured by MHC class I antigen induction. Jak1, Jak2, and Stat1α were activated, and IFN-
R1 was phosphorylated only in cells expressing both IFN-
R1 and IFN-
R2. Jak2 kinase was shown to associate with the intracellular domain of the IFN-
R2.
Footnotes
-
↵* This study was supported by United States Public Health Services Grant RO1 CA46465 from the National Cancer Institute (to S. P.), National Cancer Institute Cancer Center Support Grant P30 CA21765 (to J. N. I.), Grant PO1 HL53749 from NHLBI, National Institutes of Health, and a grant from the American Lebanese Syrian Associated Charities (to J. N. I.), and New Jersey Commission on Cancer Research Fellowship 94-2006-CCR00 (to B. P.). The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore by hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
-
↵1 The abbreviations used are:
- IFN-
-
interferon
- Hu-IFN, human interferon; BS3
-
bis(sulfosuccinimidyl)suberate; PBS, phosphate-buffered saline; PAGE, polyacrylamide gel electrophoresis; MHC, major histocompatibility complex; GST, glutathione S-transferase; PVDF, polyvinylidene difluoride; IL, interleukin.
- IFN-
-
↵2S. V. Kotenko and O. Silvennoinen, unpublished observation.
-
- Received March 30, 1995.
- Revision received June 20, 1995.
- © 1995 by The American Society for Biochemistry and Molecular Biology, Inc.
