Signaling by human herpesvirus 8 kaposin A through direct membrane recruitment of cytohesin-1
Signaling by human herpesvirus 8 kaposin A through direct membrane recruitment of cytohesin-1
复制标题
DOI：
10.1016/s1097-2765(01)00227-1
复制
发表时间：
2001-04-01
期刊：
影响因子：
16
通讯作者：
Haas, J
中科院分区：
文献类型：
--
作者：
Kliche, S;Nagel, W;Haas, J
通过病毒诱导转化的细胞表型需要通过病毒蛋白调节信号传导途径。我们在这里表明，诱导的人疱疹病毒8型的卡泊辛A蛋白的表型变化介导的直接相互作用与细胞粘连蛋白-1，ARF GTP酶和调节剂的鸟嘌呤核苷酸交换因子整合素介导的细胞粘附。焦点形成，应力纤维溶解和ERK-1/2 MAP激酶信号级联的激活被细胞粘连素-1 E157 K突变体逆转，该突变体缺乏催化鸟嘌呤核苷酸交换。此外，脂质体包埋的Kaposin A在体外特异性刺激肉豆蔻酰化的ARF 1的细胞粘连蛋白-1依赖性GTP结合。这些结果表明，以前未知的参与ARF GTP酶在控制细胞功能的疱疹病毒。
The induction of a transformed cellular phenotype by viruses requires the modulation of signaling pathways through viral proteins. We show here that the phenotypic changes induced by the kaposin A protein of human herpesvirus 8 are mediated through its direct interaction with cytohesin-1, a guanine nucleotide exchange factor for ARF GTPases and regulator of integrin-mediated cell adhesion. Focus formation, stress fiber dissolution, and activation of the ERK-1/2 MAP kinase signal cascade were reverted by the cytohesin-1 E157K mutant, which is deficient in catalyzing guanine nucleotide exchange. Furthermore, liposome-embedded kaposin A specifically stimulates cytohesin-1 dependent GTP binding of myristoylated ARF1 in vitro. These results suggest a previously unknown involvement of ARF GTPases in the control of cellular functions by herpesviruses.