Linked Life Data

17904606

Source:http://linkedlifedata.com/resource/pubmed/id/17904606

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pubmed-article:17904606pubmed:abstractTextThe 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.lld:pubmed
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pubmed-article:17904606pubmed:articleTitleNovel (n)PKC kinases phosphorylate Nef for increased HIV transcription, replication and perinuclear targeting.lld:pubmed
pubmed-article:17904606pubmed:affiliationUniversity of Miami, Miller School of Medicine, Department of Microbiology and Immunology, BCRI 739, Miami, FL 33136, USA.lld:pubmed
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