       Document 0626
 DOCN  M9630626
 TI    HIV-1 Tat directly interacts with the interferon-induced,
       double-stranded RNA-dependent kinase, PKR.
 DT    9603
 AU    McMillan NA; Chun RF; Siderovski DP; Galabru J; Toone WM; Samuel CE; Mak
       TW; Hovanessian AG; Jeang KT; Williams BR; Department of Cancer Biology,
       Cleveland Clinic Foundation, Ohio; 44195, USA.
 SO    Virology. 1995 Nov 10;213(2):413-24. Unique Identifier : AIDSLINE
       MED/96074517
 AB    We present evidence that the HIV-1 Tat protein and the RNA-dependent
       cellular protein kinase, PKR, interact with each other both in vitro and
       in vivo. Using GST fusion chromatography, we demonstrate that PKR,
       interacts directly with the HIV-1 Tat protein. The region in Tat
       sufficient for binding PKR maps within amino acids 20 to 72. In in vitro
       assays, the two-exon form of Tat (Tat 86) was phosphorylated by PKR,
       while the one exon form of Tat (Tat 72) inhibited PKR
       autophosphorylation and substrate phosphorylation. The ability of Tat to
       interact with PKR was demonstrated in both yeast and mammalian cells.
       Expression of PKR in yeast results in a growth suppressor phenotype
       which was reversed by coexpression of a one exon form of Tat. Expression
       of Tat 72 in HeLa cells resulted in direct interaction with PKR as
       detected by coimmunprecipitation with a Tat antibody. Tat and PKR also
       form a coimmunoprecipitable complex in cell-free extracts prepared from
       productively infected T lymphocytes. The interaction of Tat with PKR
       provides a potential mechanism by which HIV could suppress the
       interferon system.
 DE    Cell Line  Gene Products, tat/CHEMISTRY/*METABOLISM  Hela Cells  Human
       HIV-1/*METABOLISM  Interferons/PHARMACOLOGY  Phosphorylation
       Protein-Serine-Threonine Kinases/*METABOLISM  Recombinant Fusion
       Proteins/METABOLISM  Saccharomyces cerevisiae/GENETICS  Support,
       Non-U.S. Gov't  Support, U.S. Gov't, P.H.S.  T-Lymphocytes/VIROLOGY
       JOURNAL ARTICLE

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

