Document Detail

TIMP-2 is required for efficient activation of proMMP-2 in vivo.
MedLine Citation:
PMID:  10827175     Owner:  NLM     Status:  MEDLINE    
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.
Z Wang; R Juttermann; P D Soloway
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Publication Detail:
Type:  Journal Article; Research Support, U.S. Gov't, P.H.S.    
Journal Detail:
Title:  The Journal of biological chemistry     Volume:  275     ISSN:  0021-9258     ISO Abbreviation:  J. Biol. Chem.     Publication Date:  2000 Aug 
Date Detail:
Created Date:  2000-09-25     Completed Date:  2000-09-25     Revised Date:  2013-06-11    
Medline Journal Info:
Nlm Unique ID:  2985121R     Medline TA:  J Biol Chem     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  26411-5     Citation Subset:  IM    
Roswell Park Cancer Institute, Department of Molecular and Cellular Biology, Buffalo, New York 16263, USA.
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MeSH Terms
Enzyme Activation
Enzyme Precursors / metabolism*
Gelatinases / metabolism*
Matrix Metalloproteinases, Membrane-Associated
Metalloendopeptidases / metabolism*
Mice, Inbred C57BL
Mice, Knockout
Tissue Inhibitor of Metalloproteinase-1 / metabolism
Tissue Inhibitor of Metalloproteinase-2 / deficiency,  physiology*
Grant Support
CA 16056/CA/NCI NIH HHS; EY 11279/EY/NEI NIH HHS; R01 EY011279/EY/NEI NIH HHS; R01 EY011279-04/EY/NEI NIH HHS
Reg. No./Substance:
0/Enzyme Precursors; 0/Tissue Inhibitor of Metalloproteinase-1; 127497-59-0/Tissue Inhibitor of Metalloproteinase-2; EC 3.4.24.-/Gelatinases; EC 3.4.24.-/Matrix Metalloproteinases, Membrane-Associated; EC 3.4.24.-/Metalloendopeptidases; EC 3.4.24.-/progelatinase

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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