Nunn M F, Marsh J W
Laboratory of Molecular Biology, National Institute of Mental Health, Bethesda, Maryland 20892, USA.
J Virol. 1996 Sep;70(9):6157-61. doi: 10.1128/JVI.70.9.6157-6161.1996.
Although human immunodeficiency virus (HIV) Nef is essential for the induction of AIDS, its biochemical function has remained an enigma. In this study, HIV Nef protein is shown to associate with a serine-threonine kinase that recognizes histone H4 as a substrate, is serologically related to rat p21-activated kinase (PAK), and is specifically activated by Rac and Cdc42. These characteristics define the Nef-associated kinase as belonging to the PAK family. PAKs initiate kinase cascades in response to environmental stimuli, and their identification as a target of Nef implicates these signaling molecules in HIV pathogenesis and provides a novel target for clinical intervention.
尽管人类免疫缺陷病毒(HIV)Nef蛋白对于艾滋病的诱发至关重要,但其生化功能一直是个谜。在本研究中,HIV Nef蛋白被证明与一种丝氨酸-苏氨酸激酶相关联,该激酶将组蛋白H4识别为底物,在血清学上与大鼠p21激活激酶(PAK)相关,并且被Rac和Cdc42特异性激活。这些特征将Nef相关激酶定义为属于PAK家族。PAK响应环境刺激启动激酶级联反应,它们被鉴定为Nef的靶点,这表明这些信号分子参与了HIV发病机制,并为临床干预提供了一个新靶点。