Binding of IFN gamma and its C-terminal peptide to a cytoplasmic domain of its receptor that is essential for function.
We have previously shown that murine interferon gamma (IFN gamma) binds to a soluble form of its receptor via both the N-terminus and C-terminus. The IFN gamma N-terminus binds extracellular receptor residues 95-120. Here we report that the C-terminus of IFN gamma binds to the membrane proximal region of the cytoplasmic domain of the receptor, residues 253-287. Peptide binding to fixed/permeabilized cells is specifically blocked by anti-(253-287) antibodies. These data suggest a novel mechanism by which IFN gamma binds to its receptor, involving both the extracellular and the intracellular receptor domains. Such a mechanism could have broader implications for the activation of signal transduction pathways by both IFN gamma and other cytokines whose receptors are members of the cytokine receptor superfamily.
Szente
B E
BE
Department of Microbiology, University of Florida, Gainesville 32611.
Johnson
H M
HM
D000595:Amino Acid Sequence; D000818:Animals; D003600:Cytosol / Q000378:metabolism; D007371:Interferon-gamma / Q000378:metabolism*; D007739:L Cells; D051379:Mice; D008969:Molecular Sequence Data; D010446:Peptide Fragments / Q000378:metabolism; D017471:Receptors, Interferon / Q000737:chemistry / Q000378:metabolism*; D012995:Solubility; D000096743:Interferon gamma Receptor
D007371:Interferon-gamma; D010446:Peptide Fragments; D017471:Receptors, Interferon; D000096743:Interferon gamma Receptor