Source:http://linkedlifedata.com/resource/pubmed/id/17904606
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| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
1
|
| pubmed:dateCreated |
2007-12-6
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| pubmed:abstractText |
The N-terminus of the human immunodeficiency virus (HIV) pathogenicity factor Nef associates with a protein complex (NAKC for Nef-associated kinase complex) that contains at least two kinases: the tyrosine kinase Lck and a serine kinase activity which was found to phosphorylate Lck and the Nef N-terminus. Here we show that this serine kinase activity is mediated by members of the novel Protein Kinase C (nPKC) subfamily, PKCdelta and theta. Association with the Nef N-terminus was sufficient to activate PKC leading to phosphorylation of Nef in vitro on a conserved serine residue at position 6. Mutation of serine 6 or coexpression of a transdominant negative PKC mutant significantly reduced Nef-stimulated HIV transcription and replication in resting PBMC. When analyzing the molecular mechanisms, we found that mutating serine 6 moderately affected myristoylation of Nef and its association with Pak2 activity, whereas CD4 downmodulation was not inhibited. More interestingly, this mutation abolished the typical perinuclear localization of Nef in T cells. We conclude that the activation of nPKCs by Nef is required to increase viral replication/infectivity and direct the subcellular localization of Nef.
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| pubmed:language |
eng
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| pubmed:journal | |
| pubmed:citationSubset |
IM
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| pubmed:chemical | |
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jan
|
| pubmed:issn |
0042-6822
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| pubmed:author |
pubmed-author:BaurAndreas SAS,
pubmed-author:BlumeKatjaK,
pubmed-author:FacklerOliver TOT,
pubmed-author:GieseSimone ISI,
pubmed-author:HallerClaudiaC,
pubmed-author:KrautkrämerEllenE,
pubmed-author:SassGabrieleG,
pubmed-author:TrappSusannaS,
pubmed-author:WitteVanessaV,
pubmed-author:WolfDietlindeD
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| pubmed:issnType |
Print
|
| pubmed:day |
5
|
| pubmed:volume |
370
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| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
45-54
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:17904606-Amino Acid Sequence,
pubmed-meshheading:17904606-Animals,
pubmed-meshheading:17904606-COS Cells,
pubmed-meshheading:17904606-Cell Line,
pubmed-meshheading:17904606-Cercopithecus aethiops,
pubmed-meshheading:17904606-Genes, nef,
pubmed-meshheading:17904606-HIV-1,
pubmed-meshheading:17904606-Humans,
pubmed-meshheading:17904606-Jurkat Cells,
pubmed-meshheading:17904606-Molecular Sequence Data,
pubmed-meshheading:17904606-Multienzyme Complexes,
pubmed-meshheading:17904606-Phosphorylation,
pubmed-meshheading:17904606-Protein Kinase C,
pubmed-meshheading:17904606-Protein Kinase C-delta,
pubmed-meshheading:17904606-Subcellular Fractions,
pubmed-meshheading:17904606-Transcription, Genetic,
pubmed-meshheading:17904606-Virus Replication,
pubmed-meshheading:17904606-nef Gene Products, Human Immunodeficiency Virus
|
| pubmed:year |
2008
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| pubmed:articleTitle |
Novel (n)PKC kinases phosphorylate Nef for increased HIV transcription, replication and perinuclear targeting.
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| pubmed:affiliation |
University of Miami, Miller School of Medicine, Department of Microbiology and Immunology, BCRI 739, Miami, FL 33136, USA.
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| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|