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  • Title: 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.
    Author: Witte V, Laffert B, Gintschel P, Krautkrämer E, Blume K, Fackler OT, Baur AS.
    Journal: J Immunol; 2008 Dec 15; 181(12):8425-32. PubMed ID: 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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