Linked Life Data

16237100

Source:http://linkedlifedata.com/resource/pubmed/id/16237100

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
9
pubmed:dateCreated
2005-10-20
pubmed:abstractText
The HIV-1 protein Nef enhances viral pathogenicity and accelerates disease progression in vivo. Nef potentiates T cell activation by an unknown mechanism, probably by optimizing the intracellular environment for HIV replication. Using a new T cell reporter system, we have found that Nef more than doubles the number of cells expressing the transcription factors NF-kappaB and NFAT after TCR stimulation. This Nef-induced priming of TCR signaling pathways occurred independently of calcium signaling and involved a very proximal step before protein kinase C activation. Engagement of the TCR by MHC-bound Ag triggers the formation of the immunological synapse by recruiting detergent-resistant membrane microdomains, termed lipid rafts. Approximately 5-10% of the total cellular pool of Nef is localized within lipid rafts. Using confocal and real-time microscopy, we found that Nef in lipid rafts was recruited into the immunological synapse within minutes after Ab engagement of the TCR/CD3 and CD28 receptors. This recruitment was dependent on the N-terminal domain of Nef encompassing its myristoylation. Nef did not increase the number of cell surface lipid rafts or immunological synapses. Recently, studies have shown a specific interaction of Nef with an active subpopulation of p21-activated kinase-2 found only in the lipid rafts. Thus, the corecruitment of Nef and key cellular partners (e.g., activated p21-activated kinase-2) into the immunological synapse may underlie the increased frequency of cells expressing transcriptionally active forms of NF-kappaB and NFAT and the resultant changes in T cell activation.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
AIM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
0022-1767
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
175
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6050-7
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:16237100-Antigens, CD28, pubmed-meshheading:16237100-Calcium Signaling, pubmed-meshheading:16237100-Gene Products, nef, pubmed-meshheading:16237100-HIV, pubmed-meshheading:16237100-Humans, pubmed-meshheading:16237100-Jurkat Cells, pubmed-meshheading:16237100-Lymphocyte Activation, pubmed-meshheading:16237100-Membrane Microdomains, pubmed-meshheading:16237100-NF-kappa B, pubmed-meshheading:16237100-NFATC Transcription Factors, pubmed-meshheading:16237100-Protein Kinase C, pubmed-meshheading:16237100-Protein Structure, Tertiary, pubmed-meshheading:16237100-Protein-Serine-Threonine Kinases, pubmed-meshheading:16237100-Receptors, Antigen, T-Cell, pubmed-meshheading:16237100-T-Lymphocytes, pubmed-meshheading:16237100-nef Gene Products, Human Immunodeficiency Virus, pubmed-meshheading:16237100-p21-Activated Kinases
pubmed:year
2005
pubmed:articleTitle
Nef is physically recruited into the immunological synapse and potentiates T cell activation early after TCR engagement.
pubmed:affiliation
Gladstone Institute of Virology and Immunology, University of California, 94158, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't