The Tat protein of human immunodeficiency virus type 1 is a substrate and inhibitor of the interferon-induced, virally activated protein kinase, PKR

Brand, S. R., Kobayashi, R., Mathews, M. B. (March 1997) The Tat protein of human immunodeficiency virus type 1 is a substrate and inhibitor of the interferon-induced, virally activated protein kinase, PKR. Journal of Biological Chemistry, 272 (13). pp. 8388-95. ISSN 0021-9258

URL: http://www.ncbi.nlm.nih.gov/pubmed/9079663

Abstract

We demonstrate that the interferon-induced, double-stranded (ds) RNA-activated kinase, PKR, is able to bind to and phosphorylate the human immunodeficiency virus type 1 (HIV-1) trans-activating protein, Tat. Furthermore, Tat can inhibit the activation and activity of the kinase. Phosphorylation of Tat by PKR is dependent on the prior activation of PKR by dsRNA and occurs on serine and threonine residues adjacent to the basic region important for TAR RNA binding and Tat function. Activated PKR efficiently phosphorylates both the two-exon form of Tat (Tat-86) and the single exon form (Tat-72). Mutagenesis indicates that the interaction between PKR and Tat requires the RNA-binding region of Tat. Tat competes with eukaryotic initiation factor 2, a well-characterized substrate of PKR, for phosphorylation by activated PKR. Tat also inhibits the autophosphorylation of PKR by dsRNA. This biochemical evidence of an intimate relationship between Tat, an important regulator of HIV transcription, and PKR, a pleiotropic cellular regulator, may provide insights into HIV-1 pathogenesis and, more generally, virus/host interactions.

Item Type: Paper
Uncontrolled Keywords: Amino Acid Sequence Enzyme Activation Eukaryotic Initiation Factor-2/metabolism Gene Products, tat/ metabolism Hiv-1 Humans Interferons/ pharmacology Molecular Sequence Data Phosphorylation Protein Kinase C/metabolism Protein-Serine-Threonine Kinases/ metabolism Recombinant Proteins/metabolism Research Support, U.S. Gov't, P.H.S. eIF-2 Kinase
Subjects: diseases & disorders > viral diseases > HIV
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > DNA, RNA structure, function, modification > dsRNA
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein expression > phosphorylation
bioinformatics > genomics and proteomics > genetics & nucleic acid processing > protein structure, function, modification > protein types > enzymes > kinase > Protein kinase C
CSHL Authors:
Communities: CSHL labs > Kobayashi lab
Depositing User: Kathleen Darby
Date: 28 March 1997
Date Deposited: 08 May 2014 16:38
Last Modified: 08 May 2014 16:38
Related URLs:
URI: http://repository.cshl.edu/id/eprint/29975

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