title: Chimeric erythropoietin-interferon gamma receptors reveal differences in functional architecture of intracellular domains for signal transduction.
abstract: Binding of interferon gamma (IFN-gamma) causes oligomerization of the two interferon gamma receptor (IFN-gammaR) subunits, receptor chain 1 (IFN-gammaR1, the ligand-binding chain) and the second chain of the receptor (IFN-gammaR2), 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-gammaR1 and IFN-gammaR2 chains demonstrate that the architecture of the EpoR and the IFN-gammaR complexes differ significantly. Although IFN-gammaR1 alone cannot initiate signal transduction, the chimera EpoR/gammaR1 (extracellular/intracellular) generates slight responses characteristic of IFN-gamma in response to Epo and the EpoR/gammaR1. EpoR/gammaR2 heterodimer is a fully functional receptor complex. The results demonstrate that the configuration of the extracellular domains influences the architecture of the intracellular domains.
authors.affiliation: Department of Molecular Genetics and Microbiology, University of Medicine and Dentistry of New Jersey, Robert Wood Johnson Medical School, Piscataway, New Jersey 08854-5635, USA.
authors.forename: G
authors.initials: G
authors.lastname: Muthukumaran
authors.forename: S
authors.initials: S
authors.lastname: Kotenko
authors.forename: R
authors.initials: R
authors.lastname: Donnelly
authors.forename: J N
authors.initials: JN
authors.lastname: Ihle
authors.forename: S
authors.initials: S
authors.lastname: Pestka
mesh_terms: D006801:Humans; D017467:Receptors, Erythropoietin / Q000235:genetics* / Q000378:metabolism; D017471:Receptors, Interferon / Q000235:genetics* / Q000378:metabolism; D011993:Recombinant Fusion Proteins / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction; D000096743:Interferon gamma Receptor
chemical_list: D017467:Receptors, Erythropoietin; D017471:Receptors, Interferon; D011993:Recombinant Fusion Proteins; D000096743:Interferon gamma Receptor