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http://purl.uniprot.org/citations/9130696http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9130696http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/9130696http://www.w3.org/2000/01/rdf-schema#comment"Activation of furin requires autoproteolytic cleavage of its 83-amino acid propeptide at the consensus furin site, Arg-Thr-Lys-Arg107/. This RER-localized cleavage is necessary, but not sufficient, for enzyme activation. Rather, full activation of furin requires exposure to, and correct routing within, the TGN/endosomal system. Here, we identify the steps in addition to the initial propeptide cleavage necessary for activation of furin. Exposure of membrane preparations containing an inactive RER-localized soluble furin construct to either: (i) an acidic and calcium-containing environment characteristic of the TGN; or (ii) mild trypsinization at neutral pH, resulted in the activation of the endoprotease. Taken together, these results suggest that the pH drop facilitates the removal of a furin inhibitor. Consistent with these findings, following cleavage in the RER, the furin propeptide remains associated with the enzyme and functions as a potent inhibitor of the endoprotease. Co-immunoprecipitation studies coupled with analysis by mass spectrometry show that release of the propeptide at acidic pH, and hence activation of furin, requires a second cleavage within the autoinhibitory domain at a site containing a P6 arginine (-Arg70-Gly-Val-Thr-Lys-Arg75/-). The significance of this cleavage in regulating the compartment-specific activation of furin, and the relationship of the furin activation pathway to those of other serine endoproteases are discussed."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.org/dc/terms/identifier"doi:10.1093/emboj/16.7.1508"xsd:string
http://purl.uniprot.org/citations/9130696http://purl.org/dc/terms/identifier"doi:10.1093/emboj/16.7.1508"xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/author"Thomas G."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/author"Thomas G."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/author"Anderson E.D."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/author"Anderson E.D."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/author"Thulin C.D."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/author"Thulin C.D."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/author"Jean F."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/author"Jean F."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/author"VanSlyke J.K."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/author"VanSlyke J.K."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/date"1997"xsd:gYear
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/date"1997"xsd:gYear
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/name"EMBO J."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/name"EMBO J."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/pages"1508-1518"xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/pages"1508-1518"xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/title"Activation of the furin endoprotease is a multiple-step process: requirements for acidification and internal propeptide cleavage."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/title"Activation of the furin endoprotease is a multiple-step process: requirements for acidification and internal propeptide cleavage."xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/volume"16"xsd:string
http://purl.uniprot.org/citations/9130696http://purl.uniprot.org/core/volume"16"xsd:string