Linked Life Data

21550985

Source:http://linkedlifedata.com/resource/pubmed/id/21550985

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
26
pubmed:dateCreated
2011-6-27
pubmed:abstractText
Bone morphogenetic protein 10 (BMP10) is a member of the TGF-? 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.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
1083-351X
pubmed:author
pubmed:issnType
Electronic
pubmed:day
1
pubmed:volume
286
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
22785-94
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
Furin is the major processing enzyme of the cardiac-specific growth factor bone morphogenetic protein 10.
pubmed:affiliation
Laboratory of Biochemical Neuroendocrinology, Clinical Research Institute of Montreal, Université de Montréal, Montreal, Quebec H2W 1R7, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't