Source:http://linkedlifedata.com/resource/pubmed/id/15494497
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Predicate | Object |
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rdf:type | |
lifeskim:mentions | |
pubmed:issue |
9
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pubmed:dateCreated |
2004-10-20
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pubmed:abstractText |
HIV Nef down-regulates CD4 from the cell surface in the absence of CD4 phosphorylation, whereas PMA down-regulates CD4 through a phosphorylation-dependent pathway. In this study we show that the down-regulation of CD4 in human Jurkat T cells expressing Nef was nearly complete (approximately 95%), whereas that induced by PMA was partial (approximately 40%). Unexpectedly, treating T cells expressing Nef with PMA restored the surface CD4 up to 35% of the steady state level. Both mutating the phosphorylation sites in the CD4 cytoplasmic tail (Ser408 and Ser415) and the use of a protein kinase C inhibitor, bisindolylmaleimide1, abolished the restoration of surface CD4, suggesting that the restoration required CD4 phosphorylation. CD4 and Nef could be cross-linked by a chemical cross-linker, 3,3-dithiobis[sulfosuccinimidyl-propionate], in control T cell membranes, but not in PMA-treated T cell membrane, suggesting that CD4 and Nef interacted with each other in T cells, and the phosphorylation disrupted the CD4-Nef interaction. We propose that this dissociation switches CD4 internalization from the Nef-mediated, nearly complete down-regulation to a phosphorylation-dependent, partial down-regulation, resulting in a net gain of CD4 on the T cell surface.
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pubmed:language |
eng
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pubmed:journal | |
pubmed:citationSubset |
AIM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4,
http://linkedlifedata.com/resource/pubmed/chemical/Cross-Linking Reagents,
http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, nef,
http://linkedlifedata.com/resource/pubmed/chemical/Serine,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/nef Gene Products, Human...
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pubmed:status |
MEDLINE
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pubmed:month |
Nov
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pubmed:issn |
0022-1767
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pubmed:author | |
pubmed:issnType |
Print
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pubmed:day |
1
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pubmed:volume |
173
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
5495-500
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pubmed:dateRevised |
2007-11-15
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pubmed:meshHeading |
pubmed-meshheading:15494497-Antigens, CD4,
pubmed-meshheading:15494497-Cell Fractionation,
pubmed-meshheading:15494497-Cell Membrane,
pubmed-meshheading:15494497-Clone Cells,
pubmed-meshheading:15494497-Cross-Linking Reagents,
pubmed-meshheading:15494497-Down-Regulation,
pubmed-meshheading:15494497-Drug Synergism,
pubmed-meshheading:15494497-Gene Products, nef,
pubmed-meshheading:15494497-HIV,
pubmed-meshheading:15494497-Humans,
pubmed-meshheading:15494497-Jurkat Cells,
pubmed-meshheading:15494497-Phosphorylation,
pubmed-meshheading:15494497-Serine,
pubmed-meshheading:15494497-Staining and Labeling,
pubmed-meshheading:15494497-T-Lymphocyte Subsets,
pubmed-meshheading:15494497-Tetradecanoylphorbol Acetate,
pubmed-meshheading:15494497-nef Gene Products, Human Immunodeficiency Virus
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pubmed:year |
2004
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pubmed:articleTitle |
CD4 phosphorylation partially reverses Nef down-regulation of CD4.
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pubmed:affiliation |
Skirball Institute of Biomedical Research, New York University School of Medicine, New York, NY 10016, USA. jiny@saturn.med.nyu.edu
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pubmed:publicationType |
Journal Article,
Research Support, U.S. Gov't, P.H.S.,
Research Support, Non-U.S. Gov't
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