Premium
Membrane type‐1 matrix metalloprotease‐independent activation of pro‐matrix metalloprotease‐2 by proprotein convertases
Author(s) -
Koo BonHun,
Kim HeeHyun,
Park Michael Y.,
Jeon OkHee,
Kim DooSik
Publication year - 2009
Publication title -
the febs journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.981
H-Index - 204
eISSN - 1742-4658
pISSN - 1742-464X
DOI - 10.1111/j.1742-4658.2009.07335.x
Subject(s) - metalloproteinase , matrix metalloproteinase , furin , proprotein convertases , chemistry , microbiology and biotechnology , extracellular matrix , matrix metalloproteinase 3 , biochemistry , biology , enzyme , cholesterol , ldl receptor , lipoprotein
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 demonstrate membrane type‐1 matrix metalloprotease‐independent propeptide processing of matrix metalloprotease‐2 in HEK293F and various tumor cell lines, and show that proprotein convertases can mediate the processing intracellularly as well as extracellularly. Furthermore, processed matrix metalloprotease‐2 exhibits enzymatic activity that is enhanced by intermolecular autolytic cleavage. Thus, our experimental data, taken together with the broad expression of proprotein convertases, suggest that the proprotein convertase‐mediated processing may be a general activation mechanism for pro‐matrix metalloprotease‐2 in vivo .