Cellular Mechanisms for Human Procollagenase-3 (MMP-13) Activation EVIDENCE THAT MT1-MMP (MMP-14) AND GELATINASE A (MMP-2) ARE ABLE TO GENERATE ACTIVE ENZYME

摘要: Gelatinase A and membrane-type metalloproteinase (MT1-MMP) were able to process human procollagenase-3 (Mr 60,000) the fully active enzyme (Tyr85 N terminus; Mr 48,000). MT1-MMP activated via a 56,000 intermediate (Ile36 terminus) 48,000 which was result of cleavage Glu84-Tyr85 peptide bond. We have established that activation rate by enhanced in presence progelatinase A, thereby demonstrating unique new cascade consisting three members matrix family. In addition, can be plasmin, cleaved Lys38-Glu39 Arg76-Cys77 bonds propeptide domain. Autoproteolysis then resulted release rest domain generating Tyr85 N-terminal collagenase-3. However, plasmin C-terminal collagenase-3 results loss its collagenolytic activity. Concanavalin A-stimulated fibroblasts expressing fibroblast-derived plasma membranes form final which, analogy with activation, may represent model system for vivo activation. Inhibition experiments using tissue inhibitor metalloproteinases, plasminogen activator inhibitor-2, or aprotinin demonstrated cellular due MT1-MMP/gelatinase excluded participation serine proteinases such as during considerably potentiate crude membrane preparations from concanavalin fibroblasts, thus confirming our purified MT1-MMP. This significant breast cancer pathology, where all enzymes been implicated playing important roles.