DC Field | Value | Language |
dc.contributor.author | Wilmes, Stephan | |
dc.contributor.author | Beutel, Oliver | |
dc.contributor.author | Li, Zhi | |
dc.contributor.author | Francois-Newton, Veronique | |
dc.contributor.author | Richter, Christian P. | |
dc.contributor.author | Janning, Dennis | |
dc.contributor.author | Kroll, Cindy | |
dc.contributor.author | Hanhart, Patrizia | |
dc.contributor.author | Hoette, Katharina | |
dc.contributor.author | You, Changjiang | |
dc.contributor.author | Uze, Gilles | |
dc.contributor.author | Pellegrini, Sandra | |
dc.contributor.author | Piehler, Jacob | |
dc.date.accessioned | 2021-12-23T16:17:08Z | - |
dc.date.available | 2021-12-23T16:17:08Z | - |
dc.date.issued | 2015 | |
dc.identifier.issn | 00219525 | |
dc.identifier.uri | https://osnascholar.ub.uni-osnabrueck.de/handle/unios/12217 | - |
dc.description.abstract | Type I interferons (IFNs) activate differential cellular responses through a shared cell surface receptor composed of the two subunits, IFNAR1 and IFNAR2. We propose here a mechanistic model for how IFN receptor plasticity is regulated on the level of receptor dimerization. Quantitative single-molecule imaging of receptor assembly in the plasma membrane of living cells clearly identified IFN-induced dimerization of IFNAR1 and IFNAR2. The negative feedback regulator ubiquitin-specific protease 18 (USP18) potently interferes with the recruitment of IFNAR1 into the ternary complex, probably by impeding complex stabilization related to the associated Janus kinases. Thus, the responsiveness to IFN alpha 2 is potently down-regulated after the first wave of gene induction, while IFN beta, due to its similar to 100-fold higher binding affinity, is still able to efficiently recruit IFNAR1. Consistent with functional data, this novel regulatory mechanism at the level of receptor assembly explains how signaling by IFN beta is maintained over longer times compared with IFN alpha 2 as a temporally encoded cause of functional receptor plasticity. | |
dc.description.sponsorship | Deutsche ForschungsgemeinschaftGerman Research Foundation (DFG) [Sonderforschungsbereich 944]; European Community's Seventh Framework Program (FP7) [223608]; Institut PasteurEuropean Commission; Centre National pour la Recherche Scientifique; Institut National de la Sante et de la Recherche Medicate; Ligue contre le CancerLigue nationale contre le cancer; This project was supported by funding from the Deutsche Forschungsgemeinschaft (Sonderforschungsbereich 944) to J. Piehler and by the European Community's Seventh Framework Program (FP7/2007-2013) under grant agreement no. 223608 (IFNaction) to J. Piehler, S. Pellegrini, and G. Uze. S. Pellegrini was supported by Institut Pasteur, Centre National pour la Recherche Scientifique, and Institut National de la Sante et de la Recherche Medicate. V. Francois-Newton was supported by the Ligue contre le Cancer. | |
dc.language.iso | en | |
dc.publisher | ROCKEFELLER UNIV PRESS | |
dc.relation.ispartof | JOURNAL OF CELL BIOLOGY | |
dc.subject | ALPHA/BETA-RECEPTOR | |
dc.subject | Cell Biology | |
dc.subject | CELL-SURFACE | |
dc.subject | ERYTHROPOIETIN RECEPTOR | |
dc.subject | IFN-BETA | |
dc.subject | LIGAND-BINDING | |
dc.subject | MUTATIONAL ANALYSIS | |
dc.subject | POLYMER-SUPPORTED MEMBRANES | |
dc.subject | RESONANCE ENERGY-TRANSFER | |
dc.subject | SINGLE-MOLECULE TRACKING | |
dc.subject | TRANSMEMBRANE DOMAIN | |
dc.title | Receptor dimerization dynamics as a regulatory valve for plasticity of type I interferon signaling | |
dc.type | journal article | |
dc.identifier.doi | 10.1083/jcb.201412049 | |
dc.identifier.isi | ISI:000355643900014 | |
dc.description.volume | 209 | |
dc.description.issue | 4 | |
dc.description.startpage | 579 | |
dc.description.endpage | 593 | |
dc.contributor.orcid | 0000-0002-7839-6397 | |
dc.contributor.orcid | 0000-0001-5837-7589 | |
dc.contributor.orcid | 0000-0001-5837-7589 | |
dc.contributor.orcid | 0000-0003-4422-4914 | |
dc.contributor.orcid | 0000-0002-4112-710X | |
dc.contributor.orcid | 0000-0002-4150-5772 | |
dc.contributor.researcherid | L-3901-2014 | |
dc.contributor.researcherid | O-6383-2019 | |
dc.contributor.researcherid | G-5546-2015 | |
dc.contributor.researcherid | Y-6351-2019 | |
dc.contributor.researcherid | Q-4790-2018 | |
dc.identifier.eissn | 15408140 | |
dc.publisher.place | 950 THIRD AVE, 2ND FLR, NEW YORK, NY 10022 USA | |
dcterms.isPartOf.abbreviation | J. Cell Biol. | |
dcterms.oaStatus | Green Published, Green Submitted | |
crisitem.author.dept | Sonderforschungsbereich 944: Physiologie und Dynamik zellulärer Mikrokompartimente | - |
crisitem.author.dept | FB 05 - Biologie/Chemie | - |
crisitem.author.deptid | organisation19 | - |
crisitem.author.deptid | fb05 | - |
crisitem.author.orcid | 0000-0002-7839-6397 | - |
crisitem.author.orcid | 0000-0002-2143-2270 | - |
crisitem.author.parentorg | FB 05 - Biologie/Chemie | - |
crisitem.author.parentorg | Universität Osnabrück | - |
crisitem.author.grandparentorg | Universität Osnabrück | - |
crisitem.author.netid | YoCh745 | - |
crisitem.author.netid | PiJa938 | - |