Matrix metalloproteinase 3 (stromelysin) activates the precursor for the human matrix metalloproteinase 9.
Matrix metalloproteinase 9 (MMP-9), also known as 92-kDa gelatinase/type IV collagenase, is secreted from neutrophils, macrophages, and a number of transformed cells in zymogen form. Here we report that matrix metalloproteinase 3 (MMP-3/stromelysin) is an activator of the precursor of matrix metalloproteinase 9 (proMMP-9). MMP-3 initially cleaves proMMP-9 at the Glu40-Met41 bond located in the middle of the propeptide to generate an 86-kDa intermediate. Cleavage of this bond triggers a change in proMMP-9 that renders the Arg87-Phe88 bond susceptible to the second cleavage by MMP-3, resulting in conversion to an 82-kDa form. alpha 2-Macroglobulin binding studies of partially activated MMP-9 demonstrate that the 82-kDa species is proteolytically active, but not the initial intermediate of 86 kDa. This stepwise activation mechanism of proMMP-9 is analogous to those of other members of the MMP family, but the action of MMP-3 on proMMP-9 is the first example of zymogen activation that can be triggered by another member of the MMP family. The results imply that MMP-3 may be an effective activator of proMMP-9 in vivo.
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Related Subject Headings
- alpha-Macroglobulins
- Molecular Sequence Data
- Microbial Collagenase
- Metalloendopeptidases
- Matrix Metalloproteinase 9
- Matrix Metalloproteinase 3
- Humans
- Enzyme Precursors
- Enzyme Activation
- Electrophoresis, Polyacrylamide Gel
Citation
Published In
DOI
EISSN
ISSN
Publication Date
Volume
Issue
Start / End Page
Related Subject Headings
- alpha-Macroglobulins
- Molecular Sequence Data
- Microbial Collagenase
- Metalloendopeptidases
- Matrix Metalloproteinase 9
- Matrix Metalloproteinase 3
- Humans
- Enzyme Precursors
- Enzyme Activation
- Electrophoresis, Polyacrylamide Gel