Selective involvement of TIMP-2 in the second activational cleavage of pro-MMP-2: refinement of the pro-MMP-2 activation mechanism
Selective involvement of TIMP-2 in the second activational cleavage of pro-MMP-2: refinement of the pro-MMP-2 activation mechanism
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DOI：
10.1016/s0014-5793(03)01094-9
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发表时间：
2003-10-23
期刊：
影响因子：
3.5
通讯作者：
Thompson, EW
中科院分区：
文献类型：
--
作者：
Lafleur, MA;Tester, AM;Thompson, EW
在膜1型NIMP（MT 1-MMP）转染的MCF-7细胞中鉴定了一种金属蛋白酶组织抑制剂-2（TIMP-2）独立机制，用于产生基质金属蛋白酶原-2（MMP-2）的第一次活化裂解，并在TIMP-2缺陷的成纤维细胞中得到证实。相比之下，第二MMP-2激活步骤被发现是TIMP-2依赖在这两个系统。发现MMP-2血红素结合蛋白C-末端结构域对于第一步处理是关键的，证实了膜系留的需要。我们建议，MMP-2的中间物种形成了完善的三分子复合物（MT 1-MMP/TIMP-2/MMP 2）进一步TIMP-2依赖性自催化裂解的完全活性物种。这种替代机制可以补充传统的TIMP-2介导的第一步机制。(C)2003年由Elsevier B. V.代表欧洲生物化学学会联合会出版。
A tissue inhibitor of metalloproteinases-2 (TIMP-2)independent mechanism for generating the first activational cleavage of pro-matrix metalloproteinase-2 (MMP-2) was identified in membrane type-1 NIMP (MT1-MMP)-transfected MCF-7 cells and confirmed in TIMP-2-deficient fibroblasts. In contrast, the second MMP-2-activational step was found to be TIMP-2 dependent in both systems. MMP-2 hemopexin C-terminal domain was found to be critical for the first step processing, confirming a need for membrane tethering. We propose that the intermediate species of MMP-2 forms the well-established trimolecular complex (MT1-MMP/TIMP-2/MMP2) for further TIMP-2-dependent autocatalytic cleavage to the fully active species. This alternate mechanism may supplement the traditional TIMP-2-mediated first step mechanism. (C) 2003 Published by Elsevier B.V. on behalf of the Federation of European Biochemical Societies.