Source:http://linkedlifedata.com/resource/pubmed/id/16492675
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
17
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| pubmed:dateCreated |
2006-4-24
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| pubmed:abstractText |
Cell-surface proteoglycans have been shown to modulate transforming growth factor (TGF)-beta responsiveness in epithelial cells and other cell types. However, the proteoglycan (heparan sulfate or chondroitin sulfate) involved in modulation of TGF-beta responsiveness and the mechanism by which it modulates TGF-beta responsiveness remain unknown. Here we demonstrate that TGF-beta1 induces transcriptional activation of plasminogen activator inhibitor-1 (PAI-1) and growth inhibition more potently in CHO cell mutants deficient in heparan sulfate (CHO-677 cells) than in wild-type CHO-K1 cells. 125I-TGF-beta1 affinity labeling analysis of cell-surface TGF-beta receptors reveals that CHO-K1 and CHO-677 cells exhibit low (<1) and high (>1) ratios of 125I-TGF-beta1 binding to TbetaR-II and TbetaR-I, respectively. Receptor-bound 125I-TGF-beta1 undergoes nystatin-inhibitable rapid degradation in CHO-K1 cells but not in CHO-677 cells. In Mv1Lu cells (which, like CHO-K1 cells, exhibit nystatin-inhibitable rapid degradation of receptor-bound 125I-TGF-beta1), treatment with heparitinase or a heparan sulfate biosynthesis inhibitor results in a change from a low (<1) to a high (>1) ratio of 125I-TGF-beta1 binding to TbetaR-II and TbetaR-I and enhanced TGF-beta1-induced transcriptional activation of PAI-1. Sucrose density gradient analysis indicates that a significant fraction of TbetaR-I and TbetaR-II is localized in caveolae/lipid-raft fractions in CHO-K1 and Mv1Lu cells whereas the majority of the TGF-beta receptors are localized in non-lipid-raft fractions in CHO-677 cells. These results suggest that heparan sulfate negatively modulates TGF-beta1 responsiveness by decreasing the ratio of TGF-beta1 binding to TbetaR-II and TbetaR-I, facilitating caveolae/lipid-raft-mediated endocytosis and rapid degradation of TGF-beta1, thus diminishing non-lipid-raft-mediated endocytosis and signaling of TGF-beta1 in these epithelial cells.
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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/Activin Receptors, Type I,
http://linkedlifedata.com/resource/pubmed/chemical/Heparitin Sulfate,
http://linkedlifedata.com/resource/pubmed/chemical/Nystatin,
http://linkedlifedata.com/resource/pubmed/chemical/Plasminogen Activator Inhibitor 1,
http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Transforming Growth...,
http://linkedlifedata.com/resource/pubmed/chemical/TGF-beta type I receptor,
http://linkedlifedata.com/resource/pubmed/chemical/Thymidine,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta,
http://linkedlifedata.com/resource/pubmed/chemical/Transforming Growth Factor beta1,
http://linkedlifedata.com/resource/pubmed/chemical/transforming growth factor-beta...
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| pubmed:status |
MEDLINE
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| pubmed:month |
Apr
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| pubmed:issn |
0021-9258
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| pubmed:author | |
| pubmed:issnType |
Print
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| pubmed:day |
28
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| pubmed:volume |
281
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| pubmed:owner |
NLM
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| pubmed:authorsComplete |
Y
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| pubmed:pagination |
11506-14
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| pubmed:dateRevised |
2009-11-19
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| pubmed:meshHeading |
pubmed-meshheading:16492675-Activin Receptors, Type I,
pubmed-meshheading:16492675-Animals,
pubmed-meshheading:16492675-CHO Cells,
pubmed-meshheading:16492675-Caveolae,
pubmed-meshheading:16492675-Cell Proliferation,
pubmed-meshheading:16492675-Cricetinae,
pubmed-meshheading:16492675-Endocytosis,
pubmed-meshheading:16492675-Epithelial Cells,
pubmed-meshheading:16492675-Heparitin Sulfate,
pubmed-meshheading:16492675-Lung,
pubmed-meshheading:16492675-Nystatin,
pubmed-meshheading:16492675-Plasminogen Activator Inhibitor 1,
pubmed-meshheading:16492675-Protein-Serine-Threonine Kinases,
pubmed-meshheading:16492675-Receptors, Transforming Growth Factor beta,
pubmed-meshheading:16492675-Thymidine,
pubmed-meshheading:16492675-Transforming Growth Factor beta,
pubmed-meshheading:16492675-Transforming Growth Factor beta1
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| pubmed:year |
2006
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| pubmed:articleTitle |
Cellular heparan sulfate negatively modulates transforming growth factor-beta1 (TGF-beta1) responsiveness in epithelial cells.
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| pubmed:affiliation |
Department of Biochemistry and Molecular Biology, Saint Louis University School of Medicine, St. Louis, Missouri 63104, USA.
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| pubmed:publicationType |
Journal Article
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