Chimeric erythropoietin-interferon γ receptors reveal differences in functional architecture of intracellular domains for signal transduction

Abstract

Binding of interferon gamma (IFN-γ) causes oligomerization of the two interferon γ receptor (IFN-γR) subunits, receptor chain 1 (IFN-γR1, the ligand-binding chain) and the second chain of the receptor (IFN-γR2), and causes activation of two Jak kinases (Jak1 and Jak2). In contrast, the erythropoietin receptor (EpoR) requires only one receptor chain and one Jak kinase (Jak2). Chimeras between the EpoR and the IFN-γR1 and IFN-γR2 chains demonstrate that the architecture of the EpoR and the IFN-γR complexes differ significantly. Although IFN-γR1 alone cannot initiate signal transduction, the chimera EpoR/γR1 (extracellular/intracellular) generates slight responses characteristic of IFN-γ in response to Epo and the EpoR/γR1·EpoR/γR2 heterodimer is a fully functional receptor complex. The results demonstrate that the configuration of the extracellular domains influences the architecture of the intracellular domains.