Pro-MMP-9 activation by the MT1-MMP/MMP-2 axis and MMP-3: role of TIMP-2 and plasma membranes.
Pro-MMP-9 activation by the MT1-MMP/MMP-2 axis and MMP-3: role of TIMP-2 and plasma membranes.
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DOI：
10.1016/s0006-291x(03)01405-0
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发表时间：
2003-08
影响因子：
3.1
通讯作者：
M. Tóth;Irina Chvyrkova;M. Bernardo;Sonia Hernandez-Barrantes;R. Fridman
中科院分区：
文献类型：
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作者：
M. Tóth;Irina Chvyrkova;M. Bernardo;Sonia Hernandez-Barrantes;R. Fridman
MMP-9（明胶酶B）以潜伏形式（前MMP-9）产生，需要激活才能达到催化活性。之前，我们发现MMP-2（明胶酶A）是溶液中pro-MMP-9的激活剂。然而，在培养细胞中，即使存在MMP-2，前mmp -9仍以潜伏形式存在。由于pro-MMP-2在细胞表面被MT1-MMP激活，这一过程需要TIMP-2，因此我们研究了MT1-MMP/MMP-2轴和TIMPs在介导pro-MMP-9激活中的作用。完整的pro-MMP-9激活是通过由MT1-MMP启动并由MMP-2介导的酶原激活级联完成的，该过程受到TIMPs的严格调控。我们发现TIMP-2通过调节pro-MMP-2激活也可以作为pro-MMP-9激活的正调节因子。此外，MMP-2或MMP-3在纯化的质膜组分中比在可溶性相或活细胞中更有效地激活pro-MMP-9，这表明细胞周围空间中pro-MMP-9的浓度可能有利于活化和催化能力。
MMP-9 (gelatinase B) is produced in a latent form (pro-MMP-9) that requires activation to achieve catalytic activity. Previously, we showed that MMP-2 (gelatinase A) is an activator of pro-MMP-9 in solution. However, in cultured cells pro-MMP-9 remains in a latent form even in the presence of MMP-2. Since pro-MMP-2 is activated on the cell surface by MT1-MMP in a process that requires TIMP-2, we investigated the role of the MT1-MMP/MMP-2 axis and TIMPs in mediating pro-MMP-9 activation. Full pro-MMP-9 activation was accomplished via a cascade of zymogen activation initiated by MT1-MMP and mediated by MMP-2 in a process that is tightly regulated by TIMPs. We show that TIMP-2 by regulating pro-MMP-2 activation can also act as a positive regulator of pro-MMP-9 activation. Also, activation of pro-MMP-9 by MMP-2 or MMP-3 was more efficient in the presence of purified plasma membrane fractions than activation in a soluble phase or in live cells, suggesting that concentration of pro-MMP-9 in the pericellular space may favor activation and catalytic competence.