Inactivating mutation of the mouse tissue inhibitor of metalloproteinases-2(Timp-2) gene alters proMMP-2 activation
Research output: Contribution to journal › Journal article › Research › peer-review
To understand the biologic function of TIMP-2, a member of the tissue inhibitors of metalloproteinases family, an inactivating mutation was introduced in the mouse Timp-2 gene by homologous recombination. Outbred homozygous mutants developed and procreated indistinguishably from wild type littermates, suggesting that fertility, development, and growth are not critically dependent on TIMP-2. Lack of functional TIMP-2, however, dramatically altered the activation of proMMP-2 both in vivo and in vitro. Fully functional TIMP-2 is essential for efficient activation of proMMP-2 in vivo. No evidence of successful functional compensation was observed. The results illustrate the duality of TIMP-2 function, i.e. at low concentrations, TIMP-2 exerts a "catalytic" or enhancing effect on cell-mediated proMMP-2 activation, whereas at higher concentrations, TIMP-2 inhibits the activation and/or activity of MMP-2.
Original language | English |
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Journal | The Journal of Biological Chemistry |
Volume | 275 |
Issue number | 34 |
Pages (from-to) | 26416-22 |
Number of pages | 7 |
ISSN | 0021-9258 |
DOIs | |
Publication status | Published - 25 Aug 2000 |
Externally published | Yes |
- Amino Acid Sequence, Animals, Base Sequence, Cells, Cultured, Enzyme Activation, Enzyme Precursors/metabolism, Female, Gelatinases/metabolism, Male, Metalloendopeptidases/metabolism, Mice, Molecular Sequence Data, Mutagenesis, Site-Directed, Protein Structure, Secondary, Recombination, Genetic, Tissue Inhibitor of Metalloproteinase-2/genetics
Research areas
ID: 201165947