| Roles of hepatocyte growth factor (HGF) activator and HGF activator inhibitor in the pericellular activation of HGF/scatter factor. | |
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MedLine Citation:
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PMID: 12784998 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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The activation of hepatocyte growth factor (HGF)/scatter factor (SF) in an extracellular milieu is a critical limiting step in HGF/SF-induced signaling that is believed to have important roles in invasive growth of tumor cells and regeneration of injured tissue. This activation is caused by a proteolytic cleavage at the bond between Arg494-Val495 in the single-chain HGF/SF precursor, generating an active two-chain heterodimeric form. The HGF activator (HGFA) is a coagulation factor XII-like serine proteinase critically involved in this process in injured tissues including tumor tissues. In the past several years, the identification of endogenous HGFA inhibitors (HAIs) has provided detailed knowledge of the regulation of HGFA activity. Currently, two types of HAIs, namely HAI-1 and HAI-2, have been reported. Both are Kunitz-type serine proteinase inhibitors and inhibit not only HGFA but also other serine proteinases, such as membrane-type serine protease 1 (matriptase), plasmin, trypsin and kallikreins. HAIs are of particular interest because they are synthesized as type-I transmembrane proteins. Therefore, HAIs must have important regulatory roles in a cell surface proteolytic reaction, which has emerged as an important mechanism for the generation of biologically active proteins mediating a diverse range of cellular functions. This review is a summary and interpretation of recent data regarding the regulation of pericellular HGF/SF activation mediated by HGFA and HAIs and includes a discussion of the possible role of the type I transmembrane Kunitz-type inhibitor in pericellular proteolysis. |
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Authors:
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Hiroaki Kataoka; Shiro Miyata; Shunro Uchinokura; Hiroshi Itoh |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't; Review |
Journal Detail:
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Title: Cancer metastasis reviews Volume: 22 ISSN: 0167-7659 ISO Abbreviation: Cancer Metastasis Rev. Publication Date: 2003 Jun-Sep |
Date Detail:
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Created Date: 2003-06-04 Completed Date: 2004-02-02 Revised Date: 2007-11-15 |
Medline Journal Info:
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Nlm Unique ID: 8605731 Medline TA: Cancer Metastasis Rev Country: United States |
Other Details:
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Languages: eng Pagination: 223-36 Citation Subset: IM |
Affiliation:
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Second Department of Pathology, Miyazaki Medical College, Miyazaki, Japan. mejina@fc.miyazaki-nea.ac.jp |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Membrane / physiology* Hepatocyte Growth Factor / physiology* Humans Membrane Glycoproteins / physiology* Neoplasms / metabolism, pathology Proteinase Inhibitory Proteins, Secretory Serine Endopeptidases / physiology* Signal Transduction |
| Chemical | |
Reg. No./Substance:
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0/Membrane Glycoproteins; 0/Proteinase Inhibitory Proteins, Secretory; 0/SPINT1 protein, human; 67256-21-7/Hepatocyte Growth Factor; EC 3.4.21.-/HGF activator; EC 3.4.21.-/Serine Endopeptidases; EC 3.4.21.-/matriptase |
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