Source:http://linkedlifedata.com/resource/pubmed/id/10748182
Switch to
| Predicate | Object |
|---|---|
| rdf:type | |
| lifeskim:mentions | |
| pubmed:issue |
22
|
| pubmed:dateCreated |
2000-7-11
|
| pubmed:abstractText |
Nef is a lentiviral protein involved in pathogenesis of AIDS, but its molecular mechanisms of action remain incompletely understood. Here we report a novel effect of Nef on lymphocyte signaling, which is mediated via a T cell receptor (TCR)-independent contribution of Nef to induction of nuclear factor of activated T cells (NFAT), a transcription factor that plays a central role in coordinating T cell activation. Expression of Nef did not significantly alter the basal level of NFAT activity in Jurkat cells nor the increased activity following T cell receptor stimulation by anti-CD3 or anti-CD3 + anti-CD28. We also mimicked NFAT induction by TCR triggering by simultaneous activation of the Ras and calcium signaling pathways with phorbol 12-myristate 13-acetate and ionomycin, respectively. Strikingly, whereas activation of either of these pathways individually did not induce NFAT activity in control cells, in Nef-expressing cells phorbol 12-myristate 13-acetate treatment alone resulted in a 100-fold increase in NFAT-directed gene expression. Experiments with different dominant negative mutant signaling proteins, inhibitory chemicals, and Lck-deficient Jurkat cells revealed that this effect was mediated via activation of calcineurin by Nef-induced changes in calcium metabolism, but was independent of TCR-associated signaling events. This ability of Nef to substitute for triggering of the calcium pathway in induction of NFAT could promote activation of human immunodeficiency virus (HIV)-infected T cells in response to stimuli mediated via TCR or other cell surface receptors under conditions when activation of Ras rather than calcium signaling would otherwise predominate.
|
| pubmed:language |
eng
|
| pubmed:journal | |
| pubmed:citationSubset |
IM
|
| pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Enzyme Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, nef,
http://linkedlifedata.com/resource/pubmed/chemical/NFATC Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/Nuclear Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinase Inhibitors,
http://linkedlifedata.com/resource/pubmed/chemical/Protein Kinases,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell,
http://linkedlifedata.com/resource/pubmed/chemical/Tetradecanoylphorbol Acetate,
http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors,
http://linkedlifedata.com/resource/pubmed/chemical/nef Gene Products, Human...,
http://linkedlifedata.com/resource/pubmed/chemical/ras Proteins
|
| pubmed:status |
MEDLINE
|
| pubmed:month |
Jun
|
| pubmed:issn |
0021-9258
|
| pubmed:author | |
| pubmed:issnType |
Print
|
| pubmed:day |
2
|
| pubmed:volume |
275
|
| pubmed:owner |
NLM
|
| pubmed:authorsComplete |
Y
|
| pubmed:pagination |
16513-7
|
| pubmed:dateRevised |
2009-11-19
|
| pubmed:meshHeading |
pubmed-meshheading:10748182-Calcium Signaling,
pubmed-meshheading:10748182-Cell Line,
pubmed-meshheading:10748182-DNA-Binding Proteins,
pubmed-meshheading:10748182-Enzyme Inhibitors,
pubmed-meshheading:10748182-Gene Products, nef,
pubmed-meshheading:10748182-HIV-1,
pubmed-meshheading:10748182-Humans,
pubmed-meshheading:10748182-MAP Kinase Signaling System,
pubmed-meshheading:10748182-NFATC Transcription Factors,
pubmed-meshheading:10748182-Nuclear Proteins,
pubmed-meshheading:10748182-Protein Kinase Inhibitors,
pubmed-meshheading:10748182-Protein Kinases,
pubmed-meshheading:10748182-Receptors, Antigen, T-Cell,
pubmed-meshheading:10748182-Tetradecanoylphorbol Acetate,
pubmed-meshheading:10748182-Transcription Factors,
pubmed-meshheading:10748182-nef Gene Products, Human Immunodeficiency Virus,
pubmed-meshheading:10748182-ras Proteins
|
| pubmed:year |
2000
|
| pubmed:articleTitle |
Synergistic activation of NFAT by HIV-1 nef and the Ras/MAPK pathway.
|
| pubmed:affiliation |
Institute of Medical Technology, University of Tampere, P. O. Box 607, FIN-33101 and the Department of Clinical Chemistry, Tampere University Hospital, P. O. Box 2000, FIN-33521, Tampere, Finland.
|
| pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|