Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2002-12-13
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.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
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
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0023-6837
pubmed:author
pubmed:issnType
Print
pubmed:volume
82
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1673-84
pubmed:dateRevised
2006-11-15
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
pubmed:year
2002
pubmed:articleTitle
Rapid trafficking of membrane type 1-matrix metalloproteinase to the cell surface regulates progelatinase a activation.
pubmed:affiliation
Department of Research, Veterans Affairs Medical Center, Northport, New York, 11768, USA. s_zucker@yahoo.com
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, Non-U.S. Gov't