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Induction of HIV transcription by Nef involves Lck activation and protein kinase C theta raft recruitment leading to activation of ERK1/2 but not NF kappa B.
- Source :
-
Journal of immunology (Baltimore, Md. : 1950) [J Immunol] 2008 Dec 15; Vol. 181 (12), pp. 8425-32. - Publication Year :
- 2008
-
Abstract
- The Nef protein of HIV-1 is a key promoter of disease progression, owing to its dramatic yet ill-defined impact on viral replication. Previously, we have shown that Nef enhances Tat-mediated transcription in a manner depending on Lck and the cytoplasmic sequestration of the transcriptional repressor embryonic ectodermal development [corrected]. In this study, we report that Lck is activated by Nef and targets protein kinase Ctheta downstream, leading to the translocation of the kinase into membrane microdomains. Although microdomain-localized protein kinase Ctheta is thought to induce the transcription factor NFkappaB, we unexpectedly failed to correlate Nef-induced signaling events with enhanced NFkappaB activity. Instead, we observed an increase in ERK MAPK activity. We conclude that Nef-mediated signaling cooperates with Nef-induced derepression and supports HIV transcription through an ERK MAPK-dependent, but NFkappaB-independent, pathway.
- Subjects :
- Cell Line
Enzyme Activation genetics
Gene Expression Regulation, Viral
Humans
Isoenzymes deficiency
Isoenzymes genetics
Jurkat Cells
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) deficiency
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) genetics
MAP Kinase Signaling System genetics
Membrane Microdomains virology
NF-kappa B metabolism
Protein Kinase C deficiency
Protein Kinase C genetics
Protein Kinase C-theta
Protein Transport genetics
T-Lymphocytes enzymology
T-Lymphocytes metabolism
T-Lymphocytes virology
Up-Regulation genetics
HIV-1 genetics
Isoenzymes physiology
Lymphocyte Specific Protein Tyrosine Kinase p56(lck) metabolism
Membrane Microdomains enzymology
Mitogen-Activated Protein Kinase 1 metabolism
Mitogen-Activated Protein Kinase 3 metabolism
Protein Kinase C physiology
nef Gene Products, Human Immunodeficiency Virus physiology
Subjects
Details
- Language :
- English
- ISSN :
- 1550-6606
- Volume :
- 181
- Issue :
- 12
- Database :
- MEDLINE
- Journal :
- Journal of immunology (Baltimore, Md. : 1950)
- Publication Type :
- Academic Journal
- Accession number :
- 19050260
- Full Text :
- https://doi.org/10.4049/jimmunol.181.12.8425