Linked Life Data

7629179

Source:http://linkedlifedata.com/resource/pubmed/id/7629179

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
31
pubmed:dateCreated
1995-9-7
pubmed:abstractText
The precursor of matrix metalloproteinase 9 (pro-MMP-9, progelatinase B) noncovalently binds to tissue inhibitor of metalloproteinases (TIMP)-1 through the C-terminal domain of each molecule. We have isolated the proMMP-9.TIMP-1 complex from the medium of human fibrosarcoma HT-1080 cells and investigated the activation processes of the complex by 4-aminophenylmercuric acetate, trypsin, and matrix metalloproteinase 3 (MMP-3, stromelysin 1). The treatment of the proMMP-9.TIMP-1 complex with 4-aminophenylmercuric acetate or trypsin converts proMMP-9 to lower molecular weight species corresponding to active forms, but no gelatinolytic activity is detected. The lack of enzymic activity results from binding of TIMP-1 to the activated MMP-9. The treatment of the proMMP-9.TIMP-1 complex with a possible physiological proMMP-9 activator, MMP-3, does not reveal any gelatinolytic activity unless the molar ratio of MMP-3 to the complex exceeds 1. This is due to the inhibition of MMP-3 by TIMP-1 forming a ternary proMMP-9.TIMP-1.MMP-3 complex. The formation of the ternary complex weakens the interaction between proMMP-9 and TIMP-1, resulting in partial dissociation of the complex into proMMP-9 and the TIMP-1.MMP-3 complex. When MMP-3 is in excess, the propeptide is completely processed, and the full activity of MMP-9 is detected. Similarly, the proMMP-9.TIMP-1 complex inhibits MMP-1 (interstitial collagenase) and in turn renders the proMMP-9 activable by a catalytic amount of MMP-3. These results suggest that formation of the proMMP-9.TIMP-1 complex regulates extracellular matrix breakdown in tissue by switching the predominant MMP activity from one type to another.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/4-aminophenylmercuriacetate, http://linkedlifedata.com/resource/pubmed/chemical/Collagenases, http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors, http://linkedlifedata.com/resource/pubmed/chemical/Glycoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Macromolecular Substances, http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 3, http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinase 9, http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases, http://linkedlifedata.com/resource/pubmed/chemical/Phenylmercuric Acetate, http://linkedlifedata.com/resource/pubmed/chemical/Tissue Inhibitor of..., http://linkedlifedata.com/resource/pubmed/chemical/Trypsin
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
4
pubmed:volume
270
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
18506-11
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed:year
1995
pubmed:articleTitle
Steps involved in activation of the pro-matrix metalloproteinase 9 (progelatinase B)-tissue inhibitor of metalloproteinases-1 complex by 4-aminophenylmercuric acetate and proteinases.
pubmed:affiliation
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City 66160-7421, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.