Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9.
Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9.
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DOI：
10.1016/s0021-9258(19)50563-4
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发表时间：
1992-02
期刊：
影响因子：
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通讯作者：
Y. Ogata;J. Enghild;H. Nagase
中科院分区：
文献类型：
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作者：
Y. Ogata;J. Enghild;H. Nagase
基质金属蛋白酶9 (MMP-9)，也被称为92-kDa明胶酶/ IV型胶原酶，由中性粒细胞、巨噬细胞和许多转化细胞以酶原形式分泌。本文报道基质金属蛋白酶3 （MMP-3/stromelysin）是基质金属蛋白酶9 （proMMP-9）前体的激活剂。MMP-3首先在位于前肽中间的Glu40-Met41键上切割proMMP-9，产生一个86 kda的中间产物。该键的切割触发了proMMP-9的变化，使Arg87-Phe88键容易被MMP-3第二次切割，从而转化为82-kDa形式。部分活化的MMP-9的α 2-巨球蛋白结合研究表明，82-kDa物种具有蛋白水解活性，但不是86 kDa的初始中间体。proMMP-9的这种逐步激活机制类似于MMP家族的其他成员，但MMP-3对proMMP-9的作用是可以由MMP家族的另一成员触发的酶原激活的第一个例子。提示MMP-3在体内可能是proMMP-9的有效激活剂。
Matrix metalloproteinase 9 (MMP-9), also known as 92-kDa gelatinase/type IV collagenase, is secreted from neutrophils, macrophages, and a number of transformed cells in zymogen form. Here we report that matrix metalloproteinase 3 (MMP-3/stromelysin) is an activator of the precursor of matrix metalloproteinase 9 (proMMP-9). MMP-3 initially cleaves proMMP-9 at the Glu40-Met41 bond located in the middle of the propeptide to generate an 86-kDa intermediate. Cleavage of this bond triggers a change in proMMP-9 that renders the Arg87-Phe88 bond susceptible to the second cleavage by MMP-3, resulting in conversion to an 82-kDa form. alpha 2-Macroglobulin binding studies of partially activated MMP-9 demonstrate that the 82-kDa species is proteolytically active, but not the initial intermediate of 86 kDa. This stepwise activation mechanism of proMMP-9 is analogous to those of other members of the MMP family, but the action of MMP-3 on proMMP-9 is the first example of zymogen activation that can be triggered by another member of the MMP family. The results imply that MMP-3 may be an effective activator of proMMP-9 in vivo.