Linked Life Data

10388555

Source:http://linkedlifedata.com/resource/pubmed/id/10388555

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
1
pubmed:dateCreated
1999-8-3
pubmed:abstractText
Human immunodeficiency virus type 1 (HIV-1) Nef is important for viral infectivity and pathogenicity. HIV-1 infection is associated with inappropriate activation and defects in the function of monocytes/macrophages. We have studied the effects of HIV-1 Nef in the murine (RAW264.7) and human (THP-1) monocyte-macrophage cell lines. Investigation of the activator protein-1 (AP-1) transcription factor showed that Nef expression induced both its DNA binding and transcriptional activities. Increased AP-1 DNA binding activity in RAW264.7 cells was associated with raised levels of c-Fos expression and induction of mRNA for the AP-1 responsive tissue inhibitor of metalloproteinases-1 (TIMP-1) gene. Mutagenesis and kinase inhibition studies were employed to determine signaling pathways used by Nef to induce AP-1. Data from these studies indicated that induction of AP-1 by Nef is likely to be mediated through the MAPK (ERK1 and 2) signaling pathway and requires the proline-rich PxxP motif of Nef, suggesting the involvement of upstream protein kinases belonging to the Src family. Effects of Nef on AP-1 induction were cell lineage-specific, being stimulatory in macrophages, inhibitory in T cells and without effect in HeLa cells. These latter two observations led us to test the possibility that cell-specific interactions of Nef with Src family proteins may modulate AP-1 activity. To this end we demonstrated that a dominant-negative Hck mutant caused inhibition of Nef-mediated AP-1 DNA binding activity in RAW cells. In conclusion, induction of AP-1 by Nef is a specific feature of human and murine macrophage cell lines that requires signal transduction events involving Hck and MAPKs.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jul
pubmed:issn
0022-2836
pubmed:author
pubmed:copyrightInfo
Copyright 1999 Academic Press.
pubmed:issnType
Print
pubmed:day
2
pubmed:volume
290
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
21-35
pubmed:dateRevised
2009-11-19
pubmed:meshHeading
pubmed-meshheading:10388555-Base Sequence, pubmed-meshheading:10388555-Calcium-Calmodulin-Dependent Protein Kinases, pubmed-meshheading:10388555-Cell Line, pubmed-meshheading:10388555-DNA Primers, pubmed-meshheading:10388555-DNA-Binding Proteins, pubmed-meshheading:10388555-Gene Expression Regulation, Viral, pubmed-meshheading:10388555-Gene Products, nef, pubmed-meshheading:10388555-Genes, fos, pubmed-meshheading:10388555-HIV-1, pubmed-meshheading:10388555-Humans, pubmed-meshheading:10388555-Macrophages, pubmed-meshheading:10388555-Protein-Tyrosine Kinases, pubmed-meshheading:10388555-Proto-Oncogene Proteins, pubmed-meshheading:10388555-Proto-Oncogene Proteins c-hck, pubmed-meshheading:10388555-Signal Transduction, pubmed-meshheading:10388555-Transcription Factor AP-1, pubmed-meshheading:10388555-Transfection, pubmed-meshheading:10388555-nef Gene Products, Human Immunodeficiency Virus
pubmed:year
1999
pubmed:articleTitle
Induction of activator protein 1 (AP-1) in macrophages by human immunodeficiency virus type-1 NEF is a cell-type-specific response that requires both hck and MAPK signaling events.
pubmed:affiliation
Southampton General Hospital, Southampton, SO16 6YD, UK.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't