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M9630626.TXT
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1996-02-27
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38 lines
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).