Plasma Membrane-bound Tissue Inhibitor of Metalloproteinases (TIMP)-2 Specifically Inhibits Matrix Metalloproteinase 2 (Gelatinase A) Activated on the Cell Surface
| Autor: | Kazushi Iwata, Yoshifumi Itoh, Hideaki Nagase, Akira Ito, Yo Mori, Kazuhiko Tanzawa |
|---|---|
| Rok vydání: | 1998 |
| Předmět: |
Gelatinase A
Cell CHO Cells Matrix metalloproteinase Hydroxamic Acids Transfection Biochemistry Extracellular matrix Cricetinae Concanavalin A medicine Animals Humans Collagenases Molecular Biology Cells Cultured Tissue Inhibitor of Metalloproteinase-2 Metalloproteinase biology Chemistry Cell Membrane Uterus Metalloendopeptidases Cell migration Cell Biology Fibroblasts Molecular biology Recombinant Proteins Cell biology Enzyme Activation Molecular Weight Kinetics Membrane medicine.anatomical_structure Matrix Metalloproteinase 9 Gelatinases biology.protein Matrix Metalloproteinase 2 Female Matrix Metalloproteinase 3 |
| Zdroj: | Journal of Biological Chemistry. 273:24360-24367 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.273.38.24360 |
| Popis: | The cell-surface activation of pro-matrix metalloproteinase 2 (pro-MMP-2) is considered to be critical for cell migration and invasion. Treatment of human uterine cervical fibroblasts with concanavalin A activates pro-MMP-2 on the cell surface by converting it to the 65-kDa form with a minor form of 45 kDa. However, the 65-kDa MMP-2 was inactivated by tissue inhibitor of metalloproteinases (TIMP)-2 that was bound to the plasma membrane upon concanavalin A treatment. TIMP-2 binds to the plasma membrane through its N-terminal domain by two different modes of interaction as follows: one is sensitive to a hydroxamate (HXM) inhibitor of MMPs and the other is HXM-insensitive. TIMP-2 bound to the membrane in a HXM-insensitive manner, comprising about 40-50% of TIMP-2 on the membrane, is the inhibitor of the cell surface-activated MMP-2. It, however, does not inhibit MMP-3, MMP-9, and the 45-kDa MMP-2 lacking the C-terminal domain. The inhibition of the 65-kDa MMP-2 by TIMP-2 is initiated by the interaction of their C-terminal domains. Subsequently, the MMP-2.TIMP-2 complex is released from the membrane, and the activity of MMP-2 is blocked by TIMP-2. In the presence of collagen types I, II, III, V, or gelatin, the rate of inhibition of the 65-kDa MMP-2 by the membrane-bound TIMP-2 decreased considerably. These results suggest that the pericellular activity of MMP-2 is tightly regulated by membrane-bound TIMP-2 and surrounding extracellular matrix components. |
| Databáze: | OpenAIRE |
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