SPECIFIC INTERACTION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TAT PROTEINS WITH A CELLULAR PROTEIN-KINASE
SPECIFIC INTERACTION OF THE HUMAN-IMMUNODEFICIENCY-VIRUS TAT PROTEINS WITH A CELLULAR PROTEIN-KINASE
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DOI：
10.1006/viro.1993.1634
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发表时间：
1993-12-01
期刊：
影响因子：
3.7
通讯作者：
RICE, AP
中科院分区：
文献类型：
--
作者：
HERRMANN, CH;RICE, AP
人类免疫缺陷病毒1型和2型（HIV-1和HIV-2）达特蛋白是相关的转录激活因子，其作用可能由细胞因子介导。利用体外激酶试验，我们已经证明HIV-2的达特蛋白和HIV-1的达特蛋白的活化结构域特异性地结合细胞蛋白激酶。在体内消除反式激活活性的达特突变体在体外消除了与激酶结合的能力。这是第一次证明与达特结合的细胞因子对达特的功能活化结构域具有特异性，并显示出生物化学活性。此外，我们还发现HIV-2的达特蛋白在体外可作为激酶的底物。与体外结果一致，HIV-2的达特蛋白与HIV-2 Tat转染细胞中的细胞激酶相互作用，并在体内被磷酸化。这些结果表明，细胞丝氨酸/苏氨酸激酶可能作为一个调解人的达特功能。
The human immunodeficiency virus types 1 and 2 (HIV-1 and HIV-2) Tat proteins are related transcriptional activators whose effects are likely to be mediated by a cellular factor. Using anin vitrokinase assay, we have shown that the Tat protein of HIV-2 and the activation domain of the Tat protein of HIV-1 specifically bind to a cellular protein kinase. Mutations in Tat that abolish transactivation activityin vivoabrogate the ability of the mutants to bind to the kinasein vitro. This is the first demonstration of a cellular factor that binds to Tat that is specific for a functional activation domain of Tat and that displays a biochemical activity. Additionally, we show that the Tat protein of HIV-2 serves as a substrate of the kinasein vitro. Consistent with thein vitroresults, the Tat protein of HIV-2 interacts with a cellular kinase in HIV-2 Tat-transfected cells and is phosphorylatedin vivo. These results suggest that a cellular serine/threonine kinase may act as a mediator of Tat function.