PMID- 9461298 OWN - NLM STAT- MEDLINE DCOM- 19980227 LR - 20220317 IS - 0014-2956 (Print) IS - 0014-2956 (Linking) VI - 250 IP - 3 DP - 1997 Dec 15 TI - Membrane-type matrix metalloproteinases 1 and 2 exhibit broad-spectrum proteolytic capacities comparable to many matrix metalloproteinases. PG - 751-7 AB - Soluble proenzyme forms of the catalytic domains of membrane-type matrix metalloproteinases 1 and 2 (MT1-MMP and MT2-MMP) and a form of MT1-MMP containing the catalytic and hemopexin domains were expressed as soluble recombinant proteins. Purified, activated forms of the MT-MMP were shown to degrade fibronectin, tenascin, nidogen, aggrecan and perlecan. Only MT2-MMP showed activity against laminin. MT1-MMP retaining the hemopexin domain was able to specifically cleave native type-I and type-III collagens into the 3/4-1/4 fragments typical of the specific collagenases. The catalytic domain alone did not retain this activity. The MT-MMP did not degrade interleukin-1beta, but, similarly to many other MMP, could process a pro [tumor necrosis factor (TNF) alpha] fusion protein to release mature TNF. However, the latter was subsequently degraded into smaller fragments. These results demonstrate that, in addition to their ability to activate other MMP, such as progelatinase A/proMMP2 and procollagenase-3/proMMP13, MT-MMP degrade a number of extracellular matrix macromolecules. Their location at the surface of cells implies that they could play a significant role in the modulation of cell-matrix interactions. FAU - d'Ortho, M P AU - d'Ortho MP AD - INSERM U296, Faculte de Medecine, Creteil, France. dortho@im3.inserm.fr FAU - Will, H AU - Will H FAU - Atkinson, S AU - Atkinson S FAU - Butler, G AU - Butler G FAU - Messent, A AU - Messent A FAU - Gavrilovic, J AU - Gavrilovic J FAU - Smith, B AU - Smith B FAU - Timpl, R AU - Timpl R FAU - Zardi, L AU - Zardi L FAU - Murphy, G AU - Murphy G LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - England TA - Eur J Biochem JT - European journal of biochemistry JID - 0107600 RN - 0 (Aggrecans) RN - 0 (Extracellular Matrix Proteins) RN - 0 (Fibronectins) RN - 0 (Heparan Sulfate Proteoglycans) RN - 0 (Interleukin-1) RN - 0 (Laminin) RN - 0 (Lectins, C-Type) RN - 0 (Membrane Glycoproteins) RN - 0 (Peptide Fragments) RN - 0 (Proteoglycans) RN - 0 (Recombinant Proteins) RN - 0 (Tenascin) RN - 0 (Tumor Necrosis Factor-alpha) RN - 0 (nidogen) RN - 143972-95-6 (perlecan) RN - 9007-34-5 (Collagen) RN - 9050-30-0 (Heparitin Sulfate) RN - EC 3.4.24.- (Collagenases) RN - EC 3.4.24.- (Gelatinases) RN - EC 3.4.24.- (Metalloendopeptidases) RN - EC 3.4.24.24 (Matrix Metalloproteinase 2) RN - EC 3.4.24.7 (Matrix Metalloproteinase 1) SB - IM MH - Aggrecans MH - Blotting, Western MH - Collagen/metabolism MH - Collagenases/chemistry/*metabolism MH - Electrophoresis, Polyacrylamide Gel MH - Enzyme Activation/physiology MH - Escherichia coli/genetics MH - Extracellular Matrix/chemistry/metabolism MH - *Extracellular Matrix Proteins MH - Fibronectins/metabolism MH - Gelatinases/chemistry/*metabolism MH - *Heparan Sulfate Proteoglycans MH - Heparitin Sulfate/metabolism MH - Humans MH - Interleukin-1/metabolism MH - Laminin/metabolism MH - Lectins, C-Type MH - Matrix Metalloproteinase 1 MH - Matrix Metalloproteinase 2 MH - Membrane Glycoproteins/metabolism MH - Metalloendopeptidases/chemistry/*metabolism MH - Peptide Fragments/metabolism MH - Proteoglycans/metabolism MH - Recombinant Proteins/chemistry/genetics/metabolism MH - Substrate Specificity MH - Tenascin/metabolism MH - Tumor Necrosis Factor-alpha/metabolism EDAT- 1998/02/14 00:00 MHDA- 1998/02/14 00:01 CRDT- 1998/02/14 00:00 PHST- 1998/02/14 00:00 [pubmed] PHST- 1998/02/14 00:01 [medline] PHST- 1998/02/14 00:00 [entrez] AID - 10.1111/j.1432-1033.1997.00751.x [doi] PST - ppublish SO - Eur J Biochem. 1997 Dec 15;250(3):751-7. doi: 10.1111/j.1432-1033.1997.00751.x.