Linked Life Data

12145314

Source:http://linkedlifedata.com/resource/pubmed/id/12145314

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
41
pubmed:dateCreated
2002-10-7
pubmed:abstractText
Up-regulation of the collagenolytic membrane type-1 matrix metalloproteinase (MT1-MMP) leads to increased MMP2 (gelatinase A) activation and MT1-MMP autolysis. The autocatalytic degradation product is a cell surface 44-kDa fragment of MT1-MMP (Gly(285)-Val(582)) in which the ectodomain consists of only the linker, hemopexin C domain and the stalk segment found before the transmembrane sequence. In the collagenases, hemopexin C domain exosites bind native collagen, which is required for triple helicase activity during collagen cleavage. Here we investigated the collagen binding properties and the role of the hemopexin C domain of MT1-MMP and of the 44-kDa MT1-MMP ectodomain in collagenolysis. Recombinant proteins, MT1-LCD (Gly(285)-Cys(508)), consisting of the linker and the hemopexin C domain, and MT1-CD (Gly(315)-Cys(508)), which consists of the hemopexin C domain only, were found to bind native type I collagen but not gelatin. Functionally, MT1-LCD inhibited collagen-induced MMP2 activation in fibroblasts, suggesting that interactions between collagen and endogenous MT1-MMP directly stimulate the cellular activation of pro-MMP2. MT1-LCD, but not MT1-CD, also blocked the cleavage of native type I collagen by MT1-MMP in vitro, indicating an important role for the MT1-MMP linker region in triple helicase activity. Similarly, soluble MT1-LCD, but not MT1-CD or peptide analogs of the MT1-MMP linker, reduced the invasion of type I collagen matrices by MDA-MB-231 cells as did the expression of recombinant 44-kDa MT1-MMP on the cell surface. Together, these studies demonstrate that generation of the 44-kDa MT1-MMP autolysis product regulates collagenolytic activity and subsequent invasive potential, suggesting a novel feedback mechanism for the control of pericellular proteolysis.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
0021-9258
pubmed:author
pubmed:issnType
Print
pubmed:day
11
pubmed:volume
277
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
39005-14
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:12145314-Amino Acid Sequence, pubmed-meshheading:12145314-Animals, pubmed-meshheading:12145314-Cells, Cultured, pubmed-meshheading:12145314-Collagen Type I, pubmed-meshheading:12145314-Enzyme Activation, pubmed-meshheading:12145314-Fibroblasts, pubmed-meshheading:12145314-Hemopexin, pubmed-meshheading:12145314-Humans, pubmed-meshheading:12145314-Matrix Metalloproteinase 2, pubmed-meshheading:12145314-Matrix Metalloproteinases, Membrane-Associated, pubmed-meshheading:12145314-Metalloendopeptidases, pubmed-meshheading:12145314-Molecular Sequence Data, pubmed-meshheading:12145314-Peptides, pubmed-meshheading:12145314-Protein Binding, pubmed-meshheading:12145314-Protein Structure, Tertiary, pubmed-meshheading:12145314-Rats, pubmed-meshheading:12145314-Recombinant Fusion Proteins, pubmed-meshheading:12145314-Sequence Alignment
pubmed:year
2002
pubmed:articleTitle
Collagen binding properties of the membrane type-1 matrix metalloproteinase (MT1-MMP) hemopexin C domain. The ectodomain of the 44-kDa autocatalytic product of MT1-MMP inhibits cell invasion by disrupting native type I collagen cleavage.
pubmed:affiliation
C.I.H.R. Group in Matrix Dynamics, Department of Biochemistry and Molecular Biology, University of British Columbia, Vancouver, British Columbia V6T 1Z3, Canada.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't