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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
4
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pubmed:dateCreated |
2002-8-21
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pubmed:databankReference |
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pubmed:abstractText |
Proteolytic cleavage of TNF receptor 1 (TNFR1) generates soluble receptors that regulate TNF bioactivity. We hypothesized that the mechanism of TNFR1 shedding might involve interactions with regulatory ectoproteins. Using a yeast two-hybrid approach, we identified ARTS-1 (aminopeptidase regulator of TNFR1 shedding) as a type II integral membrane protein that binds to the TNFR1 extracellular domain. In vivo binding of membrane-associated ARTS-1 to TNFR1 was confirmed by coimmunoprecipitation experiments using human pulmonary epithelial and umbilical vein endothelial cells. A direct relationship exists between membrane-associated ARTS-1 protein levels and concordant changes in TNFR1 shedding. Cells overexpressing ARTS-1 demonstrated increased TNFR1 shedding and decreased membrane-associated TNFR1, while cells expressing antisense ARTS-1 mRNA demonstrated decreased membrane-associated ARTS-1, decreased TNFR1 shedding, and increased membrane-associated TNFR1. ARTS-1 neither bound to TNFR2 nor altered its shedding, suggesting specificity for TNFR1. Although a recombinant ARTS-1 protein demonstrated selective aminopeptidase activity toward nonpolar amino acids, multiple lines of negative evidence suggest that ARTS-1 does not possess TNFR1 sheddase activity. These data indicate that ARTS-1 is a multifunctional ectoprotein capable of binding to and promoting TNFR1 shedding. We propose that formation of a TNFR1-ARTS-1 molecular complex represents a novel mechanism by which TNFR1 shedding is regulated.
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pubmed:commentsCorrections |
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-10220586,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-10523497,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-10799547,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-10824104,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-10978897,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-11056387,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-11226253,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-11278735,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-1310100,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-1698610,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-1850405,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-2564851,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-2572457,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-2894375,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-3943125,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-7559527,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-7594530,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-7758105,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-8137429,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-8433982,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-9034190,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-9034191,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-9177475,
http://linkedlifedata.com/resource/pubmed/commentcorrection/12189246-9812885
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/ADP Ribose Transferases,
http://linkedlifedata.com/resource/pubmed/chemical/ART1 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Aminopeptidases,
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/GPI-Linked Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Membrane Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Tumor Necrosis Factor...
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pubmed:status |
MEDLINE
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pubmed:month |
Aug
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pubmed:issn |
0021-9738
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
110
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
515-26
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pubmed:dateRevised |
2010-11-18
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pubmed:meshHeading |
pubmed-meshheading:12189246-ADP Ribose Transferases,
pubmed-meshheading:12189246-Amino Acid Sequence,
pubmed-meshheading:12189246-Aminopeptidases,
pubmed-meshheading:12189246-Antigens, CD,
pubmed-meshheading:12189246-Base Sequence,
pubmed-meshheading:12189246-Carrier Proteins,
pubmed-meshheading:12189246-Cell Line,
pubmed-meshheading:12189246-Cells, Cultured,
pubmed-meshheading:12189246-Cloning, Molecular,
pubmed-meshheading:12189246-Endothelium, Vascular,
pubmed-meshheading:12189246-Epithelial Cells,
pubmed-meshheading:12189246-GPI-Linked Proteins,
pubmed-meshheading:12189246-Humans,
pubmed-meshheading:12189246-Lung,
pubmed-meshheading:12189246-Membrane Proteins,
pubmed-meshheading:12189246-Molecular Sequence Data,
pubmed-meshheading:12189246-Protein Structure, Tertiary,
pubmed-meshheading:12189246-Receptors, Tumor Necrosis Factor,
pubmed-meshheading:12189246-Receptors, Tumor Necrosis Factor, Type I,
pubmed-meshheading:12189246-Tumor Cells, Cultured
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pubmed:year |
2002
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pubmed:articleTitle |
Identification of ARTS-1 as a novel TNFR1-binding protein that promotes TNFR1 ectodomain shedding.
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pubmed:affiliation |
Pulmonary-Critical Care Medicine Branch, National Heart, Lung, and Blood Institute, , National Institutes of Health, Bethesda, Maryland 20892-1590, USA.
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pubmed:publicationType |
Journal Article
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