       Document 0116
 DOCN  M9630116
 TI    Protein kinase C-zeta mediates NF-kappa B activation in human
       immunodeficiency virus-infected monocytes.
 DT    9603
 AU    Folgueira L; McElhinny JA; Bren GD; MacMorran WS; Diaz-Meco MT; Moscat
       J; Paya CV; Department of Immunology, Mayo Clinic, Rochester, Minnesota;
       55905, USA.
 SO    J Virol. 1996 Jan;70(1):223-31. Unique Identifier : AIDSLINE
       MED/96099434
 AB    The molecular mechanisms regulating human immunodeficiency virus (HIV)
       persistence in a major cell reservoir such as the macrophage remain
       unknown. NF-kappa B is a transcription factor involved in the regulation
       of the HIV long terminal repeat and is selectively activated following
       HIV infection of human macrophages. Although little information as to
       what signal transduction pathways mediate NF-kappa B activation in
       monocytes-macrophages is available, our previous work indicated that
       classical protein kinase C (PKC) isoenzymes were not involved in the
       HIV-mediated NF-kappa B activation. In this study, we have focused on
       atypical PKC isoenzymes. PKC-zeta belongs to this family and is known to
       be an important step in NF-kappa B activation in other cell systems.
       Immunoblotting experiments with U937 cells demonstrate that PKC-zeta is
       present in these cells, and its expression can be downmodulated by
       antisense oligonucleotides (AO). The HIV-mediated NF-kappa B activation
       is selectively reduced by AO to PKC-zeta. In addition, cotransfection of
       a negative dominant molecule of PKC-zeta (PKC-zeta mut) with NF-kappa
       B-dependent reporter genes selectively inhibits the HIV- but not phorbol
       myristate acetate- or lipopolysaccharide-mediated activation of NF-kappa
       B. That PKC-zeta is specific in regulating NF-kappa B is concluded from
       the inability of PKC-zeta(mut) to interfere with the basal or phorbol
       myristate acetate-inducible CREB- or AP1-dependent transcriptional
       activity. Lastly, we demonstrate a selective inhibition of p24
       production by HIV-infected human macrophages when treated with AO to
       PKC-zeta. Altogether, these results suggest that atypical PKC
       isoenzymes, including PKC-zeta, participate in the signal transduction
       pathways by which HIV infection results in the activation of NF-kappa B
       in human monocytic cells and macrophages.
 DE    Base Sequence  Cells, Cultured  Enzyme Inhibitors/PHARMACOLOGY  Human
       HIV/*PHYSIOLOGY  Molecular Sequence Data  Monocytes/METABOLISM/*VIROLOGY
       NF-kappa B/*METABOLISM  Oligonucleotides, Antisense/PHARMACOLOGY
       Protein Kinase C/ANTAGONISTS & INHIB/GENETICS/*METABOLISM  Tumor Cells,
       Cultured  Virus Replication/PHYSIOLOGY  JOURNAL ARTICLE

       SOURCE: National Library of Medicine.  NOTICE: This material may be
       protected by Copyright Law (Title 17, U.S.Code).

