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) bind s to a soluble form of its receptor via both the N-terminus and C-term inus. The IFN gamma N-terminus binds extracellular receptor residues 9 5-120. Here we report that the C-terminus of IFN gamma binds to the me mbrane proximal region of the cytoplasmic domain of the receptor, resi dues 253-287. Peptide binding to fixed/permeabilized cells is specific ally 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 mechanis m could have broader implications for the activation of signal transdu ction pathways by both IFN gamma and other cytokines whose receptors a re members. (C) 1994 Academic Press, Inc.