論文 - 詳細
| RRC ID | 6558 |
|---|---|
| 著者 | Mukai S, Fukushima T, Naka D, Tanaka H, Osada Y, Kataoka H. |
| タイトル | Activation of hepatocyte growth factor activator zymogen (pro-HGFA) by human kallikrein 1-related peptidases. |
| ジャーナル | FEBS J |
| Abstract |
Hepatocyte growth factor activator (HGFA) is a serine protease and a potent activator of prohepatocyte growth factor/scatter factor (pro-HGF/SF), a multifunctional growth factor that is critically involved in tissue morphogenesis, regeneration, and tumor progression. HGFA circulates as a zymogen (pro-HGFA) and is activated in response to tissue injury. Although thrombin is considered to be an activator of pro-HGFA, alternative pro-HGFA activation pathways in tumor microenvironments remain to be identified. In this study, we examined the effects of kallikrein 1-related peptidases (KLKs), a family of extracellular serine proteases, on the activation of pro-HGFA. Among the KLKs examined (KLK2, KLK3, KLK4 and KLK5), we identified KLK4 and KLK5 as novel activators of pro-HGFA. Using N-terminal sequencing, the cleavage site was identified as the normal processing site, Arg407-Ile408. The activation of pro-HGFA by KLK5 required a negatively charged substance such as dextran sulfate, whereas KLK4 could process pro-HGFA without dextran sulfate. KLK5 showed more efficient pro-HGFA processing than KLK4, and was expressed in 50% (13/25) of the tumor cell lines examined. HGFA processed by these KLKs efficiently activated pro-HGF/SF, and led to cellular scattering and invasion in vitro. The activities of both KLK4 and KLK5 were strongly inhibited by HGFA inhibitor type 1, an integral membrane Kunitz-type serine protease inhibitor that inhibits HGFA and other pro-HGF/SF-activating proteases. These data suggest that KLK4 and KLK5 mediate HGFA-induced activation of pro-HGF/SF within tumor tissue, which may thereafter trigger a series of events leading to tumor progression via the MET receptor. |
| 巻・号 | 275(5) |
| ページ | 1003-17 |
| 公開日 | 2008-3-1 |
| DOI | 10.1111/j.1742-4658.2008.06265.x |
| PII | EJB6265 |
| PMID | 18221492 |
| MeSH | Cell Line, Tumor Enzyme Activation Humans Kallikreins / antagonists & inhibitors Kallikreins / metabolism* Proteinase Inhibitory Proteins, Secretory / metabolism Serine Endopeptidases / metabolism* Serpins / metabolism Tissue Kallikreins / metabolism* |
| IF | 4.392 |
| 引用数 | 44 |
| WOS 分野 | BIOCHEMISTRY & MOLECULAR BIOLOGY |
| オルトメトリクス指標 |
オルトメトリクス指標項目
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| 最多言及媒体 | Patent(IFI CLAIMS) |
| 各媒体での言及数の合計 | 4 |
| 過去6か月間でのオルトメトリクス指標の変動値 | 0.0 |
| リソース情報 | |
| ヒト・動物細胞 | |