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http://purl.uniprot.org/citations/21550985http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/21550985http://www.w3.org/2000/01/rdf-schema#comment"Bone morphogenetic protein 10 (BMP10) is a member of the TGF-β superfamily and plays a critical role in heart development. In the postnatal heart, BMP10 is restricted to the right atrium. The inactive pro-BMP10 (∼60 kDa) is processed into active BMP10 (∼14 kDa) by an unknown protease. Proteolytic cleavage occurs at the RIRR(316)↓ site (human), suggesting the involvement of proprotein convertase(s) (PCs). In vitro digestion of a 12-mer peptide encompassing the predicted cleavage site with furin, PACE4, PC5/6, and PC7, showed that furin cleaves the best, whereas PC7 is inactive on this peptide. Ex vivo studies in COS-1 cells, a cell line lacking PC5/6, revealed efficient processing of pro-BMP10 by endogenous PCs other than PC5/6. The lack of processing of overexpressed pro-BMP10 in the furin- and PACE4-deficient cell line, CHO-FD11, and in furin-deficient LoVo cells, was restored by stable (CHO-FD11/Fur cells) or transient (LoVo cells) expression of furin. Use of cell-permeable and cell surface inhibitors suggested that endogenous PCs process pro-BMP10 mostly intracellularly, but also at the cell surface. Ex vivo experiments in mouse primary hepatocytes (wild type, PC5/6 knock-out, and furin knock-out) corroborated the above findings that pro-BMP10 is a substrate for endogenous furin. Western blot analyses of heart right atria extracts from wild type and PACE4 knock-out adult mice showed no significant difference in the processing of pro-BMP10, implying no in vivo role of PACE4. Overall, our in vitro, ex vivo, and in vivo data suggest that furin is the major convertase responsible for the generation of BMP10."xsd:string
http://purl.uniprot.org/citations/21550985http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m111.233577"xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/author"Bhattacharya S."xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/author"Prat A."xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/author"Benjannet S."xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/author"Hamelin J."xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/author"Seidah N.G."xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/author"Day R."xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/author"Asselin M.C."xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/author"Chamberland A."xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/author"Constam D."xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/author"Essalmani R."xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/author"Susan-Resiga D."xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/author"Szumska D."xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/date"2011"xsd:gYear
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/name"J Biol Chem"xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/pages"22785-22794"xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/title"Furin is the major processing enzyme of the cardiac-specific growth factor bone morphogenetic protein 10."xsd:string
http://purl.uniprot.org/citations/21550985http://purl.uniprot.org/core/volume"286"xsd:string
http://purl.uniprot.org/citations/21550985http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/21550985
http://purl.uniprot.org/citations/21550985http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/21550985
http://purl.uniprot.org/uniprot/#_B7ZN66-mappedCitation-21550985http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21550985
http://purl.uniprot.org/uniprot/#_P09958-mappedCitation-21550985http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21550985
http://purl.uniprot.org/uniprot/#_O95393-mappedCitation-21550985http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/21550985