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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• 作者：Toth ; Marta ; Chvyrkova ; Irina ; Bernardo ; M. Margarida ; Hernandez-Barrantes ; Sonia ; Fridman ; Rafael
• 关键词：Matrix metalloproteinases ; Protease ; Protease inhibitor ; Plasma membrane ; Zymogen
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2003
• 出版时间：August 22, 2003
• 年：2003
• 卷：308
• 期：2
• 页码：386-395
• 全文大小：317 K

文摘

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.