Intermolecular Autolytic Cleavage Can Contribute to the Activation of Progelatinase A by Cell Membranes (∗)

Membrane-type matrix metalloproteinase (MT-MMP) messenger RNA and protein expression were shown to be elevated in human fibroblasts following treatment with concanavalin A, coincident with the induction of the ability to process progelatinase A. CHO cells transfected with the cDNA for MT-MMP were ab...

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Bibliographic Details
Published in:The Journal of biological chemistry 1995-12, Vol.270 (51), p.30479-30485
Main Authors: Atkinson, Susan J., Crabbe, Thomas, Cowell, Susan, Ward, Robin V., Butler, Michael J., Sato, Hiroshi, Seiki, Motoharu, Reynolds, John J., Murphy, Gillian
Format: Article
Language:English
Subjects:
Concanavalin A - pharmacology
Enzyme Activation
Enzyme Induction
Enzyme Precursors - biosynthesis
Enzyme Precursors - metabolism
Fibroblasts - drug effects
Fibroblasts - enzymology
Gelatinases - biosynthesis
Gelatinases - metabolism
Gene Expression - drug effects
Glycoproteins - pharmacology
Humans
Kinetics
Metalloendopeptidases - biosynthesis
Metalloendopeptidases - metabolism
Mutagenesis, Site-Directed
Point Mutation
Protein Processing, Post-Translational - drug effects
Proteins - pharmacology
Recombinant Proteins - biosynthesis
Recombinant Proteins - metabolism
Tissue Inhibitor of Metalloproteinase-2
Tissue Inhibitor of Metalloproteinases
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Summary:Membrane-type matrix metalloproteinase (MT-MMP) messenger RNA and protein expression were shown to be elevated in human fibroblasts following treatment with concanavalin A, coincident with the induction of the ability to process progelatinase A. CHO cells transfected with the cDNA for MT-MMP were able to process both wild type progelatinase A and a catalytically inactive mutant, E375A progelatinase A. Both proenzymes were converted to a 68-kDa intermediate (reducing gels) form, but only the wild type enzyme was processed further to a 66-kDa end product. In contrast, both forms of progelatinase were processed via the 68-kDa intermediate to 66 kDa by concanavalin A-stimulated fibroblasts. Further study of the processing of E375A progelatinase A by plasma membrane preparations from concanavalin A-stimulated fibroblasts showed that addition of active gelatinase A enhanced processing to the mature form. It was concluded that cell membrane-mediated activation of progelatinase A could be via a cascade involving both MT-MMP and intermolecular autolytic cleavage.
ISSN:0021-9258
1083-351X
DOI:10.1074/jbc.270.51.30479