PMID: 9525598Apr 3, 1998Paper

Plasma membrane-targeted Raf kinase activates NF-kappaB and human immunodeficiency virus type 1 replication in T lymphocytes

Journal of Virology
Egbert FloryU R Rapp

Abstract

Increasing evidence points to a role of the mitogenic Ras/Raf/MEK/ERK signaling cascade in regulation of human immunodeficiency virus type 1 (HIV-1) gene expression. Stimulation of elements of this pathway leads to transactivation of the HIV-1 promoter. In particular, the NF-kappaB motif in the HIV long terminal repeat (LTR) represents a Raf-responsive element in fibroblasts. Regulation of the Raf kinase in T cells differs from findings with a variety of cell lines that the catalytic domain of Raf (Raf(delta26-303)) shows no activity. In this study, we restored the activity of the kinase in T cells by fusing its catalytic domain to the CAAX motif (-Cx) of Ras, thus targeting the enzyme to the plasma membrane. Constitutive activity of Raf was demonstrated by phosphorylation of mitogen-activated protein kinase kinase (MEK) and endogenous mitogen-activated protein kinase 1/2 (ERK1/2) in A3.01 T cells transfected with Raf(delta26-303)-Cx. Membrane-targeted Raf also stimulates NF-kappaB, as judged by kappaB-dependent reporter assays and enhanced NF-kappaB p65 binding on band shift analysis. Moreover, we found that active Raf transactivates the HIV(NL4-3) LTR in A3.01 T lymphocytes and that dominant negative Raf (C4) blocked 12-O-tet...Continue Reading

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Citations

Sep 27, 2018·Frontiers in Microbiology·Lin ChenChristian Schölz
Sep 19, 2002·The Journal of Biological Chemistry·Bernd BaumannThomas Wirth
Feb 3, 2000·Microbiology and Immunology·S Harada, Y Maeda
Apr 12, 2000·Proceedings of the National Academy of Sciences of the United States of America·B BaumannT Wirth
Aug 21, 2008·Biological Chemistry·Stephan Pleschka
May 27, 2003·International Journal of Cancer. Journal International Du Cancer·Susanne LiptayRoland M Schmid
Feb 13, 2001·The Journal of Clinical Investigation·J HiscottP Génin
Dec 1, 2001·The Journal of Biological Chemistry·Jeffrey A SchragerJon W Marsh
Aug 27, 2013·Scientific Reports·Hirotaka EbinaYoshio Koyanagi
Feb 21, 2002·The Journal of Biological Chemistry·Carsten SchellerChristian Jassoy

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