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.
J Immunol
; 181(12): 8425-32, 2008 Dec 15.
Article
en En
| MEDLINE
| ID: mdl-19050260
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.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteína Quinasa C
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VIH-1
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Proteína Quinasa 1 Activada por Mitógenos
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Proteína Tirosina Quinasa p56(lck) Específica de Linfocito
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Microdominios de Membrana
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Proteína Quinasa 3 Activada por Mitógenos
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Productos del Gen nef del Virus de la Inmunodeficiencia Humana
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Isoenzimas
Límite:
Humans
Idioma:
En
Revista:
J Immunol
Año:
2008
Tipo del documento:
Article
País de afiliación:
Alemania