tailieunhanh - Báo cáo khoa học: Membrane type-1 matrix metalloprotease-independent activation of pro-matrix metalloprotease-2 by proprotein convertases

Matrix metalloprotease-2 is implicated in many biological processes and degrades extracellular and non-extracellular matrix molecules. Matrix metalloprotease-2 maintains a latent state through a cysteine–zinc ion pairing which, when disrupted, results in full enzyme activation. This pairing can be disrupted by a conformational change or cleavage within the propeptide. | ỊFEBS Journal Membrane type-1 matrix metalloprotease-independent activation of pro-matrix metalloprotease-2 by proprotein convertases Bon-Hun Koo Hee-Hyun Kim Michael Y. Park Ok-Hee Jeon and Doo-Sik Kim Department of Biochemistry College of Life Science and Biotechnology Yonsei University Seoul South Korea Keywords furin membrane type-1 matrix metalloprotease MT1-MMP pro-matrix metalloprotease-2 pro-MMP-2 pro-MMP-2 activation proprotein convertases Correspondence . Koo Department of Biochemistry College of Life Science and Biotechnology Yonsei University 134 Sinchon-Dong Seodaemun-Gu Seoul120-749 South Korea Fax 82 2 312 6027 Tel 82 2 313 2878 E-mail k4119@ . Kim Department of Biochemistry College of Life Science and Biotechnology Yonsei University 134 Sinchon-Dong Seodaemun-Gu Seoul 120-749 South Korea Fax 82 2 312 6027 Tel 82 2 2123 2700 E-mail dskim@ Received 14 July 2009 revised 26 August 2009 accepted 28 August 2009 doi Matrix metalloprotease-2 is implicated in many biological processes and degrades extracellular and non-extracellular matrix molecules. Matrix metalloprotease-2 maintains a latent state through a cysteine-zinc ion pairing which when disrupted results in full enzyme activation. This pairing can be disrupted by a conformational change or cleavage within the propeptide. The best known activation mechanism for pro-matrix metalloprotease-2 occurs via cleavage of the propeptide by membrane type-1 matrix metalloprotease. However significant residual activation of pro-matrix metalloprotease-2 is seen in membrane type-1 matrix metalloprotease knockout mice and in fibroblasts treated with metalloprotease inhibitors. These findings indicate the presence of a membrane type-1 matrix metalloprotease-independent activation mechanism for pro-matrix metalloprotease-2 in vivo which prompted us to explore an alternative activation mechanism for pro-matrix metalloprotese-2. In this study we .