Source:http://linkedlifedata.com/resource/pubmed/id/19456860
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
13
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| pubmed:dateCreated |
2009-8-3
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| pubmed:abstractText |
Macrophage-stimulating protein (MSP) is a plasma protein that circulates as a single-chain proform. It acquires biological activity after proteolytic cleavage at the Arg483-Val484 bond, a process in which serum and cell surface serine proteinases have been implicated. In this article, we report that hepatocyte growth factor activator (HGFA), a serum proteinase which activates hepatocyte growth factor in response to tissue injury, may have a critical role in the activation of pro-MSP. In vitro analysis has revealed that human HGFA efficiently cleaves human pro-MSP at the physiological activation site without further degradation, resulting in biologically active MSP, as measured by the chemotactic response and MSP-induced morphological change of peritoneal macrophages. The processing of pro-MSP by HGFA is 10-fold more efficient than processing by factor XIa. To search for a role of HGFA in pro-MSP activation, we analyzed the processing of mouse pro-MSP in sera from HGFA-knockout (HGFA(-/-)) mice. The proform of MSP was the predominant molecular form in the plasma of both wild-type and HGFA(-/-) mice. In wild-type sera, endogenous pro-MSP was progressively converted to the mature two-chain form during incubation at 37 degrees C. However, this conversion was significantly impaired in sera from HGFA(-/-) mice. The addition of recombinant HGFA to HGFA-deficient serum restored pro-MSP convertase activity in a dose-dependent manner, and a neutralizing antibody to HGFA significantly reduced the conversion of pro-MSP in wild-type serum. Moreover, initial infiltration of macrophages into the site of mechanical skin injury was delayed in HGFA(-/-) mice. We suggest that HGFA is a major serum activator of pro-MSP.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation...,
http://linkedlifedata.com/resource/pubmed/chemical/CD68 antigen, human,
http://linkedlifedata.com/resource/pubmed/chemical/HGF activator,
http://linkedlifedata.com/resource/pubmed/chemical/Hepatocyte Growth Factor,
http://linkedlifedata.com/resource/pubmed/chemical/KLK5 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Kallikreins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Recombinant Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Serine Endopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/kallikrein 4,
http://linkedlifedata.com/resource/pubmed/chemical/macrophage stimulating protein
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| pubmed:status |
MEDLINE
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| pubmed:month |
Jul
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| pubmed:issn |
1742-4658
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| pubmed:author | |
| pubmed:issnType |
Electronic
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| pubmed:volume |
276
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
3481-90
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| pubmed:meshHeading |
pubmed-meshheading:19456860-Animals,
pubmed-meshheading:19456860-Antigens, CD,
pubmed-meshheading:19456860-Antigens, Differentiation, Myelomonocytic,
pubmed-meshheading:19456860-Enzyme Activation,
pubmed-meshheading:19456860-Hepatocyte Growth Factor,
pubmed-meshheading:19456860-Humans,
pubmed-meshheading:19456860-Kallikreins,
pubmed-meshheading:19456860-Macrophages, Peritoneal,
pubmed-meshheading:19456860-Male,
pubmed-meshheading:19456860-Mice,
pubmed-meshheading:19456860-Mice, Inbred C57BL,
pubmed-meshheading:19456860-Mice, Knockout,
pubmed-meshheading:19456860-Models, Biological,
pubmed-meshheading:19456860-Protein Precursors,
pubmed-meshheading:19456860-Proto-Oncogene Proteins,
pubmed-meshheading:19456860-Recombinant Proteins,
pubmed-meshheading:19456860-Serine Endopeptidases,
pubmed-meshheading:19456860-Serum
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| pubmed:year |
2009
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| pubmed:articleTitle |
Hepatocyte growth factor activator is a serum activator of single-chain precursor macrophage-stimulating protein.
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| pubmed:affiliation |
Section of Oncopathology and Regenerative Biology, Department of Pathology, Faculty of Medicine, University of Miyazaki, Japan.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
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