TIMP-2 Is Required for Efficient Activation of proMMP-2 in Vivo

作者：Zhiping Wang, R Jüttermann, Paul D. Soloway · 发表于：Journal of Biological Chemistry · 年份：2000 · DOI：10.1074/jbc.m001270200 · 被引用次数：395 · 研究领域：Protease and Inhibitor Mechanisms、Peptidase Inhibition and Analysis、Signaling Pathways in Disease

Matrix metalloproteinases (MMPs) are synthesized as latent proenzymes. A proteolytic cleavage event involving processing of the cysteine-rich N-terminal propeptide is required for their full activation. Previous in vitro studies indicated that activation of proMMP-2 can occur through formation of a trimolecular complex between MMP-14, TIMP-2, and proMMP-2 at the cell surface. Using TIMP-2-deficient mice and cells derived from them, TIMP-2 was shown to be required for efficient proMMP-2 activation both in vivo and in vitro. The requirement for TIMP-2 was not cell-autonomous as exogenously added TIMP-2 could restore activation of proMMP-2 to TIMP-2-deficient cells. Mutant mice were overtly normal, viable, and fertile on the C57BL/6 background, indicating that both TIMP-2 and activated proMMP-2 are dispensable for normal development.