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Interleukin-6 signaling requires EHD1-mediated alteration of membrane rafts

DC Field Value Language
dc.contributor.authorWoo, JH-
dc.contributor.authorPark, SJ-
dc.contributor.authorPark, SM-
dc.contributor.authorJoe, EH-
dc.contributor.authorJou, I-
dc.date.accessioned2023-03-24T06:27:04Z-
dc.date.available2023-03-24T06:27:04Z-
dc.date.issued2022-
dc.identifier.issn1742-464X-
dc.identifier.urihttp://repository.ajou.ac.kr/handle/201003/25130-
dc.description.abstractInterleukin-6 (IL-6) is involved in many inflammatory diseases. IL-6 binds to membrane-bound IL-6 receptor alpha (IL-6Ralpha) (classic signaling) or soluble IL-6Ralpha (trans-signaling); this complex then associates with the signal-transducing membrane protein gp130. IL-6Ralpha and gp130 float on membrane (i.e., lipid) rafts; however, how membrane rafts regulate IL-6 signaling remains unclear. Here, we demonstrate that both IL-6 classic signaling and trans-signaling depend on membrane cholesterol, an essential raft component. Super-resolution fluorescence imaging using perfringolysin O D4 fragments that selectively bind to high cholesterol concentrations revealed that IL-6 and hyper-IL-6, a fusion protein of IL-6 and soluble IL-6Ralpha, induce the alteration of membrane rafts. IL-6 and hyper-IL-6 induced D4-positive raft (D4 raft) formation without affecting cholera toxin subunit B (CTB)-positive rafts (CTB rafts). Receptor clustering of IL-6Ralpha and gp130 and STAT3 phosphorylation occurred in D4 rafts. These results indicate that D4 rafts serve as platforms for the assembly of functional IL-6 receptor complexes. We found that Eps15 homology domain-containing protein 1 (EHD1) mediates the formation of functional IL-6 receptor complexes through D4 rafts. Overall, we uncover a novel regulatory mechanism of the EHD1-mediated alteration of membrane raft in IL-6 signaling.-
dc.language.isoen-
dc.subject.MESHCholera Toxin-
dc.subject.MESHCholesterol-
dc.subject.MESHCytokine Receptor gp130-
dc.subject.MESHInterleukin-6-
dc.subject.MESHMembrane Microdomains-
dc.subject.MESHMembrane Proteins-
dc.subject.MESHReceptors, Interleukin-6-
dc.titleInterleukin-6 signaling requires EHD1-mediated alteration of membrane rafts-
dc.typeArticle-
dc.identifier.pmid35429212-
dc.subject.keywordEHD1-
dc.subject.keywordIL-6-
dc.subject.keywordinflammation-
dc.subject.keywordmembrane raft-
dc.subject.keywordSTAT3-
dc.contributor.affiliatedAuthorPark, SJ-
dc.contributor.affiliatedAuthorPark, SM-
dc.contributor.affiliatedAuthorJoe, EH-
dc.type.localJournal Papers-
dc.identifier.doi10.1111/febs.16458-
dc.citation.titleThe FEBS journal-
dc.citation.volume289-
dc.citation.number19-
dc.citation.date2022-
dc.citation.startPage5914-
dc.citation.endPage5932-
dc.identifier.bibliographicCitationThe FEBS journal, 289(19). : 5914-5932, 2022-
dc.embargo.liftdate9999-12-31-
dc.embargo.terms9999-12-31-
dc.identifier.eissn1742-4658-
dc.relation.journalidJ01742464X-
Appears in Collections:
Journal Papers > Research Organization > Inflamm-aging Translational Research Center
Journal Papers > School of Medicine / Graduate School of Medicine > Pharmacology
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