Source:http://linkedlifedata.com/resource/pubmed/id/12480917
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
12
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pubmed:dateCreated |
2002-12-13
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pubmed:abstractText |
Pericellular matrix degradation during cancer invasion and inflammation is dependent on activation of progelatinase A by membrane type 1-matrix metalloproteinase (MT1-MMP); a stoichiometric concentration of tissue inhibitor of metalloproteinase-2 (TIMP-2) is required. Activation of progelatinase A has generally been considered to be a slow process occurring as a result of enhanced expression of MT1-MMP. We herein report that ConA treatment of HT1080 fibrosarcoma cells is followed by MT1-MMP-induced activation of progelatinase A on the cell surface within 1 hour. Cell surface biotinylation, immunohistochemistry, and (125)I-labeled TIMP-2 binding to cell surface MT1-MMP were used to characterize the appearance and function of MT1-MMP on the plasma membrane. Treatment of HT1080 cells with ConA resulted in increased specific binding of (125)I-labeled TIMP-2 to cell surface receptors within 5 minutes. TIMP-2 binds almost exclusively to activated MT1-MMP on the surface of HT1080 cells. MT1-MMP function at the cell surface was also accelerated by treatment of cells with cytochalasin D, an inhibitor of actin filaments, PMA, a stimulator of protein kinase C, and bafilomycin A(1), an inhibitor of lysosome/endosome function. A functional pool of intracellular MT1-MMP available for trafficking to the cell surface was demonstrated by repetitive ConA stimulation. ConA-induced expression of MT1-MMP mRNA (Northern blot analysis) in HT1080 cells was a delayed event (>6 hours). These data suggest that presynthesized MT1-MMP is sorted to a transient storage compartment (trans-Golgi network/endosomes), where it is available for rapid trafficking to the plasma membrane and cell surface proteolytic activity.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Anti-Bacterial Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Concanavalin A,
http://linkedlifedata.com/resource/pubmed/chemical/Cytochalasin D,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Precursors,
http://linkedlifedata.com/resource/pubmed/chemical/Fluorescein-5-isothiocyanate,
http://linkedlifedata.com/resource/pubmed/chemical/Gelatinases,
http://linkedlifedata.com/resource/pubmed/chemical/Macrolides,
http://linkedlifedata.com/resource/pubmed/chemical/Matrix Metalloproteinases...,
http://linkedlifedata.com/resource/pubmed/chemical/Metalloendopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cell Surface,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Tissue Inhibitor of...,
http://linkedlifedata.com/resource/pubmed/chemical/bafilomycin A1,
http://linkedlifedata.com/resource/pubmed/chemical/progelatinase
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
0023-6837
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:volume |
82
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
1673-84
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pubmed:dateRevised |
2006-11-15
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pubmed:meshHeading |
pubmed-meshheading:12480917-Anti-Bacterial Agents,
pubmed-meshheading:12480917-Cell Membrane,
pubmed-meshheading:12480917-Concanavalin A,
pubmed-meshheading:12480917-Cytochalasin D,
pubmed-meshheading:12480917-Enzyme Activation,
pubmed-meshheading:12480917-Enzyme Precursors,
pubmed-meshheading:12480917-Fibrosarcoma,
pubmed-meshheading:12480917-Fluorescein-5-isothiocyanate,
pubmed-meshheading:12480917-Gelatinases,
pubmed-meshheading:12480917-Humans,
pubmed-meshheading:12480917-Macrolides,
pubmed-meshheading:12480917-Matrix Metalloproteinases, Membrane-Associated,
pubmed-meshheading:12480917-Metalloendopeptidases,
pubmed-meshheading:12480917-Protein Transport,
pubmed-meshheading:12480917-Receptors, Cell Surface,
pubmed-meshheading:12480917-Tetradecanoylphorbol Acetate,
pubmed-meshheading:12480917-Tissue Inhibitor of Metalloproteinase-2,
pubmed-meshheading:12480917-Tumor Cells, Cultured
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pubmed:year |
2002
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pubmed:articleTitle |
Rapid trafficking of membrane type 1-matrix metalloproteinase to the cell surface regulates progelatinase a activation.
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pubmed:affiliation |
Department of Research, Veterans Affairs Medical Center, Northport, New York, 11768, USA. s_zucker@yahoo.com
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, Non-P.H.S.,
Research Support, Non-U.S. Gov't
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