The Tat protein of human immunodeficiency virus type 1 is a substrate and inhibitor of the interferon-induced, virally activated protein kinase, PKR
The Tat protein of human immunodeficiency virus type 1 is a substrate and inhibitor of the interferon-induced, virally activated protein kinase, PKR
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DOI：
10.1074/jbc.272.13.8388
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发表时间：
1997-03-28
影响因子：
4.8
通讯作者：
Mathews, MB
中科院分区：
文献类型：
--
作者：
Brand, SR;Kobayashi, R;Mathews, MB
我们证明了干扰素诱导的双链rna激活激酶PKR能够结合并磷酸化人类免疫缺陷病毒1型（HIV-1）反式激活蛋白Tat。此外，Tat可以抑制激酶的激活和活性，PKR对Tat的磷酸化依赖于dsRNA对PKR的事先激活，并且发生在对TAR RNA结合和Tat功能重要的基本区域附近的丝氨酸和苏氨酸残基上。激活的PKR有效地磷酸化Tat的双外显子形式（Tat-86）和单外显子形式（Tat-72）。诱变表明PKR和Tat之间的相互作用需要Tat的rna结合区，Tat与真核起始因子2竞争，后者是PKR的一个很好的底物，被激活的PKR磷酸化。Tat还能通过dsRNA抑制PKR的自磷酸化。这一生物化学证据表明，Tat是HIV转录的重要调节剂，PKR是多效性细胞调节剂，这可能为HIV-1的发病机制以及更普遍的病毒/宿主相互作用提供见解。
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.