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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
6
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pubmed:dateCreated |
2006-2-7
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pubmed:abstractText |
The tissue inhibitors of metalloproteinases (TIMPs) regulate matrix metalloproteinase activity required for cell migration/invasion associated with cancer progression and angiogenesis. TIMPs also modulate cell proliferation in vitro and angiogenesis in vivo independent of their matrix metalloproteinase inhibitory activity. Here, we show that TIMP-2 mediates G1 growth arrest in human endothelial cells through de novo synthesis of the cyclin-dependent kinase inhibitor p27Kip1. TIMP-2-mediated inhibition of Cdk4 and Cdk2 activity is associated with increased binding of p27Kip1 to these complexes in vivo. Protein-tyrosine phosphatase inhibitors or expression of a dominant negative Shp-1 mutant ablates TIMP-2 induction of p27Kip1. Finally, angiogenic responses to fibroblast growth factor-2 and vascular endothelial growth factor-A in "motheaten viable" Shp-1-deficient mice are resistant to TIMP-2 inhibition, demonstrating that Shp-1 is an important negative regulator of angiogenesis in vivo.
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pubmed:grant |
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-10075712,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-10409697,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-10477552,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-10559916,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-10662779,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-10742145,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-10773440,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-11042184,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-11134082,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-11290537,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-11416152,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-11684441,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-11726503,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-11834522,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-11902577,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-12093740,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-12244303,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-12707026,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-12730128,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-12778132,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-12826400,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-12887919,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-12900406,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-12904305,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-15530852,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-7579691,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-7693724,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-7954814,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-8245788,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-9614138,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-9740804,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-9835626,
http://linkedlifedata.com/resource/pubmed/commentcorrection/16326706-9927492
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 2,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase 4,
http://linkedlifedata.com/resource/pubmed/chemical/Cyclin-Dependent Kinase Inhibitor...,
http://linkedlifedata.com/resource/pubmed/chemical/Intracellular Signaling Peptides...,
http://linkedlifedata.com/resource/pubmed/chemical/PTPN6 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatase...,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Tyrosine Phosphatases,
http://linkedlifedata.com/resource/pubmed/chemical/Ptpn6 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/Tissue Inhibitor of...,
http://linkedlifedata.com/resource/pubmed/chemical/Vascular Endothelial Growth Factor A
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
0021-9258
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:day |
10
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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 |
3711-21
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pubmed:dateRevised |
2009-11-19
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pubmed:meshHeading |
pubmed-meshheading:16326706-Humans,
pubmed-meshheading:16326706-Animals,
pubmed-meshheading:16326706-Mice,
pubmed-meshheading:16326706-Mutation,
pubmed-meshheading:16326706-Phosphorylation,
pubmed-meshheading:16326706-Microscopy, Fluorescence,
pubmed-meshheading:16326706-Cells, Cultured,
pubmed-meshheading:16326706-Endothelium, Vascular,
pubmed-meshheading:16326706-Genes, Dominant,
pubmed-meshheading:16326706-Models, Biological,
pubmed-meshheading:16326706-Subcellular Fractions,
pubmed-meshheading:16326706-Microcirculation,
pubmed-meshheading:16326706-Cell Cycle,
pubmed-meshheading:16326706-G1 Phase,
pubmed-meshheading:16326706-Cell Proliferation,
pubmed-meshheading:16326706-Gene Expression Regulation,
pubmed-meshheading:16326706-Transfection,
pubmed-meshheading:16326706-Immunoprecipitation,
pubmed-meshheading:16326706-Neovascularization, Physiologic,
pubmed-meshheading:16326706-Intracellular Signaling Peptides and Proteins,
pubmed-meshheading:16326706-Vascular Endothelial Growth Factor A,
pubmed-meshheading:16326706-Blotting, Northern
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