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PMID: 10827175 Published · ppublish English Journal Article Research Support, U.S. Gov't, P.H.S.

TIMP-2 is required for efficient activation of proMMP-2 in vivo.

The Journal of biological chemistry ·Vol. 275 ·No. 34 ·2000-08-25 ·Pages 26411-5

Wang Z, Juttermann R, Soloway PD

Abstract

Matrix metalloproteinases (MMPs) are synthesized as latent proenzymes. A proteolytic cleavage event involving processing of the cysteine-rich N-terminal propeptide is required for their full activation. Previous in vitro studies indicated that activation of proMMP-2 can occur through formation of a trimolecular complex between MMP-14, TIMP-2, and proMMP-2 at the cell surface. Using TIMP-2-deficient mice and cells derived from them, TIMP-2 was shown to be required for efficient proMMP-2 activation both in vivo and in vitro. The requirement for TIMP-2 was not cell-autonomous as exogenously added TIMP-2 could restore activation of proMMP-2 to TIMP-2-deficient cells. Mutant mice were overtly normal, viable, and fertile on the C57BL/6 background, indicating that both TIMP-2 and activated proMMP-2 are dispensable for normal development.

MeSH Terms
Animals Cattle Enzyme Activation Enzyme Precursors/metabolism Gelatinases/metabolism Matrix Metalloproteinases, Membrane-Associated Metalloendopeptidases/metabolism Mice Mice, Inbred C57BL Mice, Knockout Tissue Inhibitor of Metalloproteinase-1/metabolism Tissue Inhibitor of Metalloproteinase-2/deficiency,physiology
Chemicals
Enzyme Precursors Tissue Inhibitor of Metalloproteinase-1 Tissue Inhibitor of Metalloproteinase-2 Gelatinases Matrix Metalloproteinases, Membrane-Associated Metalloendopeptidases progelatinase
Authors & Affiliations
3 authors, click to expand affiliations / ORCID
Wang Z
Roswell Park Cancer Institute, Department of Molecular and Cellular Biology, Buffalo, New York 16263, USA.
Juttermann R
Soloway P D
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Article Info
Journal
The Journal of biological chemistry
Abbr.
J Biol Chem
ISSN
0021-9258
DOI
10.1074/jbc.M001270200
Published
2000-08-25
Pages
26411-5
Language
English
Region
United States
NLM ID
2985121R
PMCID
PMC2683068
Subset
IM
Grants
NCI NIH HHS · P30 CA016056 · United States
NCI NIH HHS · CA 16056 · United States
NEI NIH HHS · EY 11279 · United States
NEI NIH HHS · R01 EY011279-04 · United States
NEI NIH HHS · R01 EY011279 · United States
External Links
PubMed source DOI: 10.1074/jbc.M001270200 PMC Full Text View journal details
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