Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
1997-3-31
pubmed:abstractText
The Nef protein alters T cell receptor (TCR) signaling in T cells and is critical for the pathogenesis of AIDS. We used a transient expression assay in a human CD4+ T cell line to analyze the interaction of Nef with the TCR machinery. We show that, in addition to down-regulating CD4 expression on the cell surface, Nef blocks a receptor-proximal event in CD3 signaling. Analysis of a large number of mutant Nef proteins demonstrated that the effects of Nef on CD4 expression and on CD3 signaling are separable. The ability of Nef to block CD3 signaling was selectively abolished by mutations in the central part of the Nef protein and in particular by those known to disrupt the SH3 binding surface in the structured core of Nef. In contrast, the ability of Nef to down-regulate CD4 expression was selectively abolished by two clusters of mutations, one in the N-terminal and one in the C-terminal region of Nef. These two regions correspond to the two flexible loops in Nef as predicted by solution NMR analysis. We show that this general functional organization is conserved between the Nef proteins of the human and simian immunodeficiency viruses (HIV-1 and SIV). Our data demonstrate that Nef has at least two independent mechanisms to alter TCR function and thus may interfere with a range of T cell responses.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-1322497, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-1384720, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-1534242, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-2014052, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-2032289, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-2078405, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-2302733, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-2838547, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-6260373, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-7481804, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-7541845, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-7584145, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-7590226, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-7664345, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-7797518, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-7808489, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-7831289, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-7859737, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-7903679, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-7909325, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8035515, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8043040, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8095017, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8098729, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8108442, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8113676, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8124721, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8125254, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8262036, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8293463, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8526891, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8598486, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8599760, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8636073, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8681387, http://linkedlifedata.com/resource/pubmed/commentcorrection/9049297-8709241
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD3, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, CD4, http://linkedlifedata.com/resource/pubmed/chemical/Antigens, Differentiation..., http://linkedlifedata.com/resource/pubmed/chemical/CD69 antigen, http://linkedlifedata.com/resource/pubmed/chemical/DNA-Binding Proteins, http://linkedlifedata.com/resource/pubmed/chemical/GTF2H1 protein, human, http://linkedlifedata.com/resource/pubmed/chemical/Gene Products, nef, http://linkedlifedata.com/resource/pubmed/chemical/Lectins, C-Type, http://linkedlifedata.com/resource/pubmed/chemical/Phosphoproteins, http://linkedlifedata.com/resource/pubmed/chemical/Protein-Serine-Threonine Kinases, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Antigen, T-Cell, http://linkedlifedata.com/resource/pubmed/chemical/Transcription Factors, TFII, http://linkedlifedata.com/resource/pubmed/chemical/nef Gene Products, Human...
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0261-4189
pubmed:author
pubmed:issnType
Print
pubmed:day
17
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
673-84
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
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