SIGNALING STEPS INVOLVING THE CYTOPLASMIC DOMAIN OF THE INTERFERON-GAMMA RECEPTOR ALPHA-SUBUNIT ARE NOT SPECIES-SPECIFIC

The ligand binding chain of the interferon-gamma receptor (IFN-gamma R ) is a unique cell surface protein which has no similarities to other cytokine receptors. Expression of this receptor chain (alpha-subunit) is not sufficient to mediate responsiveness to IFN-gamma. We and other s have shown that IFN-gamma-mediated signal transduction requires a sp ecies-specific interaction of the extracellular portion of the known I FN-gamma receptor alpha-chain with an additional receptor subunit that was cloned recently and designated IFN-gamma R beta-chain or accessor y factor 1. Here, we investigated whether this tight species barrier a lso ap plies to signaling events mediated by the cytoplasmic receptor domain. A cell line derived from embryos that lack the IFN-gamma R alp ha-subunit was reconstituted with a hybrid mouse-human alpha-subunit t hat consisted of an extracellular murine and transmembrane and cytopla smic human domains. The experiments reported herein showed that in mou se cells, the human intracellular domain of the hybrid IFN-gamma R alp ha-subunit was fully functional and that, therefore, signaling steps i nvolving this domain are not species-specific.