Interferon γ signals via a high-affinity multisubunit receptor complex that contains two types of polypeptide chain

S. A. Marsters, D. Pennica, E. Bach, R. D. Schreiber, A. Ashkenazi

Research output: Contribution to journalArticlepeer-review

86 Scopus citations

Abstract

Signaling by interferon γ (IFN-γ) requires two structuraLly related cell surface proteins: a ligand-binding polypeptide, known as the IFN-γ receptor (IFN-γR), and an accessory factor. However, it is not known whether IFN-γ, forms a ternary complex with the IFN-γR and accessory factor to initiate signaling. Here we demonstrate complex formation between IFN-γ and the two proteins, both in solution and at the cell surface. We observe complexes containing ligand, two molecules of IFN-γR (designated the IFN-γR a chain), and one or two molecules of accessory factor (designated the IFN-γR β chain). Transfected cells expressing both IFN-γR chains bind IFN-γ with higher affinity than do cells expressing α chain alone. Anti-β-chain antibodies prevent the β chain from participating in the ligand-receptor complex, reduce the affinity for IFN-γ, and block signaling. Soluble α- or β-chain extracellular domains also inhibit function. These results demonstrate that IFN-γ signals via a high-affinity multisubunit complex that contains two types of receptor chain and suggest a potential approach to inhibiting specific actions of IFN-γ by blocking the association of receptor subunits.

Original languageEnglish
Pages (from-to)5401-5405
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume92
Issue number12
DOIs
StatePublished - 1995

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