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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
20
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pubmed:dateCreated |
2003-5-12
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pubmed:abstractText |
Bone morphogenetic protein (BMP)-1 is a zinc-dependent metalloproteinase that cleaves a variety of extracellular matrix substrates, including type I procollagen. Little is known about the site of action of BMP-1, although the extracellular matrix seems likely to be it. BMP-1 is synthesized with an N-terminal prodomain. The removal of the prodomain presumably activates the proteinase. In this study we show that the prodomain is cleaved in the trans-Golgi network (TGN) and by furin-like/paired basic proprotein convertases. Inhibitors of furin resulted in the secretion of pro-BMP-1, which could not cleave procollagen. Recombinant furin cleaved the prodomain from pro-BMP-1. Site-directed mutagenesis of the prodomain cleavage site (RSRR) to RSAA resulted in efficient secretion of pro-BMP-1. Therefore, prodomain cleavage was not required for secretion. Using peptide N-glycosidase and neuraminidase digestion to determine the post-translational status of pro-BMP-1 during its conversion to BMP-1, we showed that BMP-1 first appears in the TGN during sialylation of the molecule. Furthermore, immunofluorescence studies using an antibody to the nascent N terminus of BMP-1 showed localization to the TGN and plasma membrane. The observation that BMP-1 occurs inside the cell raises the possibility that BMP-1 might begin to cleave its substrates prior to secretion to the extracellular matrix.
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Amidohydrolases,
http://linkedlifedata.com/resource/pubmed/chemical/BMP1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Protein 1,
http://linkedlifedata.com/resource/pubmed/chemical/Bone Morphogenetic Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Brefeldin A,
http://linkedlifedata.com/resource/pubmed/chemical/DNA, Complementary,
http://linkedlifedata.com/resource/pubmed/chemical/Epitopes,
http://linkedlifedata.com/resource/pubmed/chemical/Furin,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Monensin,
http://linkedlifedata.com/resource/pubmed/chemical/Peptide-N4-(N-acetyl-beta-glucosamin...,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Subtilisins
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pubmed:status |
MEDLINE
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pubmed:month |
May
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
16
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pubmed:volume |
278
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
18478-84
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pubmed:dateRevised |
2008-11-21
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pubmed:meshHeading |
pubmed-meshheading:12637569-Amidohydrolases,
pubmed-meshheading:12637569-Blotting, Western,
pubmed-meshheading:12637569-Bone Morphogenetic Protein 1,
pubmed-meshheading:12637569-Bone Morphogenetic Proteins,
pubmed-meshheading:12637569-Brefeldin A,
pubmed-meshheading:12637569-Cell Membrane,
pubmed-meshheading:12637569-DNA, Complementary,
pubmed-meshheading:12637569-Dose-Response Relationship, Drug,
pubmed-meshheading:12637569-Epitopes,
pubmed-meshheading:12637569-Extracellular Matrix,
pubmed-meshheading:12637569-Fibroblasts,
pubmed-meshheading:12637569-Furin,
pubmed-meshheading:12637569-Gene Library,
pubmed-meshheading:12637569-Humans,
pubmed-meshheading:12637569-Metalloendopeptidases,
pubmed-meshheading:12637569-Microscopy, Fluorescence,
pubmed-meshheading:12637569-Monensin,
pubmed-meshheading:12637569-Mutagenesis, Site-Directed,
pubmed-meshheading:12637569-Peptide-N4-(N-acetyl-beta-glucosaminyl) Asparagine Amidase,
pubmed-meshheading:12637569-Plasmids,
pubmed-meshheading:12637569-Protein Binding,
pubmed-meshheading:12637569-Protein Processing, Post-Translational,
pubmed-meshheading:12637569-Protein Structure, Tertiary,
pubmed-meshheading:12637569-Recombinant Proteins,
pubmed-meshheading:12637569-Subtilisins,
pubmed-meshheading:12637569-Transfection,
pubmed-meshheading:12637569-Tumor Cells, Cultured,
pubmed-meshheading:12637569-trans-Golgi Network
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pubmed:year |
2003
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pubmed:articleTitle |
Paired basic/Furin-like proprotein convertase cleavage of Pro-BMP-1 in the trans-Golgi network.
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pubmed:affiliation |
Wellcome Trust Centre for Cell-Matrix Research, School of Biological Sciences, University of Manchester, Stopford Building 2.205, Oxford Road, Manchester M13 9PT, United Kingdom.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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