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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 |
2005-12-16
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pubmed:abstractText |
Lentiviral Nef increases T cell signaling activity, but the molecular nature of the stimulus involved is incompletely described. We explored CD4 T cell lipid raft composition in the presence and absence of Nef. Here, the E2 ubiquitin-conjugating enzyme UbcH7, which acts in conjunction with c-Cbl, is absent from lipid rafts. This Nef-mediated exclusion is associated with failure of ubiquitination of activated Vav. In the presence of Nef, lipid raft Cdc42 is activated and forms a ternary complex between the c-Cbl-interacting protein p85Cool-1/betaPix and c-Cbl, displacing UbcH7 from rafts. Suppression of p85Cool-1/betaPix expression restores UbcH7 raft localization and Vav ubiquitination and diminishes Cdc42 activity. Moreover, p85Cool-1/betaPix knockdown attenuates HIV replication. Thresholds for activation of signaling involve the intricate balance of positive and negative regulators. Here we provide evidence for Nef disruption of a negative regulator of T cell signaling in promoting HIV replication.
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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/CBL protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Cell Cycle Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, nef,
http://linkedlifedata.com/resource/pubmed/chemical/Guanine Nucleotide Exchange Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Proto-Oncogene Proteins c-cbl,
http://linkedlifedata.com/resource/pubmed/chemical/RNA, Small Interfering,
http://linkedlifedata.com/resource/pubmed/chemical/UBE2L3 protein, human,
http://linkedlifedata.com/resource/pubmed/chemical/Ubiquitin-Conjugating Enzymes,
http://linkedlifedata.com/resource/pubmed/chemical/cdc42 GTP-Binding Protein,
http://linkedlifedata.com/resource/pubmed/chemical/nef Gene Products, Human...,
http://linkedlifedata.com/resource/pubmed/chemical/rho guanine nucleotide exchange...
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pubmed:status |
MEDLINE
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pubmed:month |
Dec
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pubmed:issn |
1074-7613
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pubmed:author |
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pubmed:issnType |
Print
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pubmed:volume |
23
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
621-34
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pubmed:dateRevised |
2008-9-11
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pubmed:meshHeading |
pubmed-meshheading:16356860-Blotting, Western,
pubmed-meshheading:16356860-CD4-Positive T-Lymphocytes,
pubmed-meshheading:16356860-Cell Cycle Proteins,
pubmed-meshheading:16356860-Cell Line,
pubmed-meshheading:16356860-Enzyme-Linked Immunosorbent Assay,
pubmed-meshheading:16356860-Gene Products, nef,
pubmed-meshheading:16356860-Guanine Nucleotide Exchange Factors,
pubmed-meshheading:16356860-HIV,
pubmed-meshheading:16356860-Humans,
pubmed-meshheading:16356860-Immunoprecipitation,
pubmed-meshheading:16356860-Membrane Microdomains,
pubmed-meshheading:16356860-Microscopy, Confocal,
pubmed-meshheading:16356860-Proto-Oncogene Proteins c-cbl,
pubmed-meshheading:16356860-RNA, Small Interfering,
pubmed-meshheading:16356860-Signal Transduction,
pubmed-meshheading:16356860-Ubiquitin-Conjugating Enzymes,
pubmed-meshheading:16356860-Virus Replication,
pubmed-meshheading:16356860-cdc42 GTP-Binding Protein,
pubmed-meshheading:16356860-nef Gene Products, Human Immunodeficiency Virus
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pubmed:year |
2005
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pubmed:articleTitle |
Nef-mediated lipid raft exclusion of UbcH7 inhibits Cbl activity in T cells to positively regulate signaling.
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pubmed:affiliation |
MRC Human Immunology Unit, Weatherall Institute of Molecular Medicine, John Radcliffe Hospital, Headington, Oxford OX3 9DS, United Kingdom. alison.simmons@molecular-medicine.oxford.ac.uk
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pubmed:publicationType |
Journal Article,
Comparative Study,
Research Support, Non-U.S. Gov't
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