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Titolo:
PLASMA MEMBRANE-TARGETED RAF KINASE ACTIVATES NF-KAPPA-B AND HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION IN T-LYMPHOCYTES
Autore:
FLORY E; WEBER CK; CHEN PF; HOFFMEYER A; JASSOY C; RAPP UR;
Indirizzi:
UNIV WURZBURG,INST MED STRAHLENKUNDE & ZELLFORSCH,VERSBACHERSTR 5 D-97078 WURZBURG GERMANY UNIV WURZBURG,INST MED STRAHLENKUNDE & ZELLFORSCH D-97078 WURZBURG GERMANY UNIV WURZBURG,INST VIROL & IMMUNBIOL D-97078 WURZBURG GERMANY
Titolo Testata:
Journal of virology
fascicolo: 4, volume: 72, anno: 1998,
pagine: 2788 - 2794
SICI:
0022-538X(1998)72:4<2788:PMRKAN>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
PROTEIN-KINASE; TRANSCRIPTION FACTOR; GENE-EXPRESSION; REQUIRES RAF-1; CELLS; BINDING; PHOSPHORYLATION; ASSOCIATION; PATHWAY; C-RAF-1;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Citazioni:
44
Recensione:
Indirizzi per estratti:
Citazione:
E. Flory et al., "PLASMA MEMBRANE-TARGETED RAF KINASE ACTIVATES NF-KAPPA-B AND HUMAN-IMMUNODEFICIENCY-VIRUS TYPE-1 REPLICATION IN T-LYMPHOCYTES", Journal of virology, 72(4), 1998, pp. 2788-2794

Abstract

Increasing evidence points to a role of the mitogenic Ras/Raf/MEK/ERKsignaling 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-kappa B motif in the HIV long terminal repeat (LTR) represents a Raf-responsive element in fibroblasts. Regulation of the Raf kinase in T cellsdiffers from findings with a variety of cell lines that the catalyticdomain of Raf (Raf(Delta 26-303)) 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(Delta 26-303)-Cx. Membrane-targeted Raf also stimulates NF-kappa B, as judged by kappa B-dependent reporter assays and enhanced NF-kappa B p65 binding on band shift analysis. Moreover, we found that active Raf transactivates the HIVNL4-3 LTR in A3.01 T lymphocytes and that dominant negative Raf (C4) blocked 12-O-tetradecanoylphorbol-13-acetate induced transactivation. When cotransfected with infectious HIVNL4-3 DNA, membrane-targeted Raf induces viral replication up to 10-fold over basal levels, as determined by the release of newly synthesized p24(gag) protein, Our study clearly demonstrates that the activity of the catalytic domain of Raf in A3.01 T cells is dependent on its cellular localization, The functional consequences of activeRaf in T lymphocytes include not only NF-kappa B activation and transactivation of the HIVNL4-3 LTR but also synthesis and release of HIV particles.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 22/09/20 alle ore 20:30:19