論文 - 詳細
| RRC ID | 35669 |
|---|---|
| 著者 | Miyamori H, Takino T, Kobayashi Y, Tokai H, Itoh Y, Seiki M, Sato H. |
| タイトル | Claudin promotes activation of pro-matrix metalloproteinase-2 mediated by membrane-type matrix metalloproteinases. |
| ジャーナル | J Biol Chem |
| Abstract |
Genes associated with regulation of membrane-type matrix metalloproteinase-1 (MT1-MMP)-mediated pro-MMP-2 processing were screened in 293T cells by a newly developed expression cloning method. One of the gene products, which promoted processing of pro-MMP-2 by MT1-MMP was claudin-5, a major component of endothelial tight junctions. Expression of claudin-5 not only replaced TIMP-2 in pro-MMP-2 activation by MT1-MMP but also promoted activation of pro-MMP-2 mediated by all MT-MMPs and MT1-MMP mutants lacking the transmembrane domain (DeltaMT1-MMP). A carboxyl-terminal deletion mutant of pro-MMP-2 (proDeltaMMP-2) was processed to an intermediate form by MT1-MMP in 293T cells and was further converted to an activated form by introduction of claudin-5. In contrast to the stimulatory effect of TIMP-2 on pro-MMP-2 activation by MT1-MMP, activation of pro-MMP-2 by DeltaMT1-MMP in the presence of claudin-5 and proDeltaMMP-2 processing by MT1-MMP were both inversely repressed by expression of exogenous TIMP-2. These results suggest that TIMP-2 is not involved in cluadin-5-induced pro-MMP-2 activation by MT-MMPs. Stimulation of MT-MMP-mediated pro-MMP-2 activation was also observed with other claudin family members, claudin-1, claudin-2, and claudin-3. Amino acid substitutions or deletions in ectodomain of claudin-1 abolished stimulatory effect. Direct interaction of claudin-1 with MT1-MMP and MMP-2 was demonstrated by immunoprecipitation analysis. MT1-MMP was co-localized with claudin-1 not only at cell-cell borders, but also at other parts of the cells. TIMP-2 enhanced cell surface localization of MMP-2 mediated by MT1-MMP, and claudin-1 also stimulated it. These results suggest that claudin recruits all MT-MMPs and pro-MMP-2 on the cell surface to achieve elevated focal concentrations and, consequently, enhances activation of pro-MMP-2. |
| 巻・号 | 276(30) |
| ページ | 28204-11 |
| 公開日 | 2001-7-27 |
| DOI | 10.1074/jbc.M103083200 |
| PII | S0021-9258(19)31627-8 |
| PMID | 11382769 |
| MeSH | Animals COS Cells Cell Line Cell Membrane / enzymology* Claudin-1 Claudin-3 Claudin-5 Claudins Cloning, Molecular DNA, Complementary / metabolism Enzyme Activation Enzyme-Linked Immunosorbent Assay Gene Deletion Gene Library Green Fluorescent Proteins Humans Luminescent Proteins / metabolism Matrix Metalloproteinase 14 Matrix Metalloproteinase 2 / metabolism* Matrix Metalloproteinases, Membrane-Associated Membrane Proteins / chemistry* Membrane Proteins / metabolism Membrane Proteins / physiology* Metalloendopeptidases / metabolism* Microscopy, Fluorescence Plasmids / metabolism Precipitin Tests Protein Binding Protein Structure, Tertiary Recombinant Fusion Proteins / metabolism Tight Junctions Tissue Inhibitor of Metalloproteinase-2 / metabolism Transfection |
| IF | 4.238 |
| 引用数 | 182 |
| 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 | Wikipedia |
| 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 | |
| 遺伝子材料 | pEAK-Claudin-5 (RDB02846) |