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http://purl.uniprot.org/citations/28060820http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28060820http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/28060820http://www.w3.org/2000/01/rdf-schema#comment"Signaling of the cytokine interleukin-6 (IL-6) via its soluble IL-6 receptor (sIL-6R) is responsible for the proinflammatory properties of IL-6 and constitutes an attractive therapeutic target, but how the sIL-6R is generated in vivo remains largely unclear. Here, we use liquid chromatography-mass spectrometry to identify an sIL-6R form in human serum that originates from proteolytic cleavage, map its cleavage site between Pro-355 and Val-356, and determine the occupancy of all O- and N-glycosylation sites of the human sIL-6R. The metalloprotease a disintegrin and metalloproteinase 17 (ADAM17) uses this cleavage site in vitro, and mutation of Val-356 is sufficient to completely abrogate IL-6R proteolysis. N- and O-glycosylation were dispensable for signaling of the IL-6R, but proteolysis was orchestrated by an N- and O-glycosylated sequon near the cleavage site and an N-glycan exosite in domain D1. Proteolysis of an IL-6R completely devoid of glycans is significantly impaired. Thus, glycosylation is an important regulator for sIL-6R generation."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.org/dc/terms/identifier"doi:10.1371/journal.pbio.2000080"xsd:string
http://purl.uniprot.org/citations/28060820http://purl.org/dc/terms/identifier"doi:10.1371/journal.pbio.2000080"xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Garbers C."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Garbers C."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Yamamoto K."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Yamamoto K."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Zhu Y."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Zhu Y."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Groetzinger J."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Groetzinger J."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Rose-John S."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Rose-John S."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Agthe M."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Agthe M."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Albrecht A."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Albrecht A."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Becker-Pauly C."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Becker-Pauly C."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Duesterhoeft S."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Duesterhoeft S."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Ehlers J.C."xsd:string
http://purl.uniprot.org/citations/28060820http://purl.uniprot.org/core/author"Ehlers J.C."xsd:string