Interferon gamma signals via a high-affinity multisubunit receptor complex that contains two types of polypeptide chain.
Signaling by interferon gamma (IFN-gamma) requires two structurally related cell surface proteins: a ligand-binding polypeptide, known as the IFN-gamma receptor (IFN-gamma R), and an accessory factor. However, it is not known whether IFN-gamma forms a ternary complex with the IFN-gamma R and accessory factor to initiate signaling. Here we demonstrate complex formation between IFN-gamma and the two proteins, both in solution and at the cell surface. We observe complexes containing ligand, two molecules of IFN-gamma R (designated the IFN-gamma R alpha chain), and one or two molecules of accessory factor (designated the IFN-gamma R beta chain). Transfected cells expressing both IFN-gamma R chains bind IFN-gamma with higher affinity than do cells expressing alpha chain alone. Anti-beta-chain antibodies prevent the beta chain from participating in the ligand-receptor complex, reduce the affinity for IFN-gamma, and block signaling. Soluble alpha- or beta-chain extracellular domains also inhibit function. These results demonstrate that IFN-gamma 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-gamma by blocking the association of receptor subunits.
Marsters
S A
SA
Department of Molecular Biology, Genentech, Inc., South San Francisco, CA 94080, USA.
Pennica
D
D
Bach
E
E
Schreiber
R D
RD
Ashkenazi
A
A
D000818:Animals; D002460:Cell Line; D007371:Interferon-gamma / Q000378:metabolism*; D051379:Mice; D011485:Protein Binding; D017471:Receptors, Interferon / Q000737:chemistry / Q000378:metabolism*; D015398:Signal Transduction; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor