Inactivating mutation of the mouse tissue inhibitor of metalloproteinases-2(Timp-2) gene alters proMMP-2 activation
Inactivating mutation of the mouse tissue inhibitor of metalloproteinases-2(Timp-2) gene alters proMMP-2 activation
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DOI：
10.1074/jbc.m001271200
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发表时间：
2000-08-25
影响因子：
4.8
通讯作者：
Birkedal-Hansen, H
中科院分区：
文献类型：
--
作者：
Caterina, JJ;Yamada, S;Birkedal-Hansen, H
为了了解TIMP-2的生物学功能，通过同源重组在小鼠TIMP-2基因中引入了一个失活突变，近亲纯合突变体的发育和繁殖与野生型幼崽没有区别，这表明生育、发育和生长并不完全依赖于TIMP-2。显著地改变了体内和体外的proMMP-2的激活。完全功能的TIMP-2是体内有效激活promp -2所必需的，没有证据表明成功的功能补偿。这些结果说明了TIMP-2的双重功能，即在低浓度下，TIMP-2对细胞介导的proMMP-2激活发挥“催化”或增强作用，而在高浓度下，TIMP-2抑制MMP-2的激活和/或活性。
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.