Herpes simplex virus 1-encoded protein kinase UL13 phosphorylates viral Us3 protein kinase and regulates nuclear localization of viral envelopment factors UL34 and UL31
Herpes simplex virus 1-encoded protein kinase UL13 phosphorylates viral Us3 protein kinase and regulates nuclear localization of viral envelopment factors UL34 and UL31
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DOI：
10.1128/jvi.80.3.1476-1486.2006
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发表时间：
2006-02-01
影响因子：
5.4
通讯作者：
Kawaguchi, Y
中科院分区：
文献类型：
--
作者：
Kato, A;Yamamoto, M;Kawaguchi, Y
UL13和US3是由单纯疱疹病毒1型编码的蛋白激酶。基于以下观察，我们在这里报道了US3是感染细胞中UL13的一种生理底物。(I)感染野生型病毒的Vero细胞的US3亚型在变性凝胶中的电泳率低于感染UL13缺失突变病毒(Delta UL13)的细胞的US3亚型的凝胶迁移率。经磷酸酶处理后，野生型病毒感染细胞的US3亚型的凝胶迁移率发生改变，其中一个亚型的迁移速度与Delta UL13感染细胞的US3亚型的迁移速度一样快。(Ii)用UL13体外磷酸化含有US3结构域的重组蛋白。(Iii)Delta UL13的表型类似于缺乏US3基因的重组病毒(Delta US3)，其病毒包膜因子UL34和UL31的定位已被证明受US3的调控。UL34和UL31在野生型病毒感染细胞的细胞核内呈光滑分布，而在Delta UL13和Delta US3感染的细胞中呈核点状分布。这些结果表明，UL13通过磷酸化US3或通过不依赖于US3的机制，使感染细胞中的US3磷酸化，并调节UL34和UL31的定位。
UL13 and Us3 are protein kinases encoded by herpes simplex virus 1. We report here that Us3 is a physiological substrate for UL13 in infected cells, based on the following observations. (i) The electrophoretic mobility, in denaturing gels, of Us3 isoforms from Vero cells infected with wild-type virus was slower than that of isoforms from cells infected with a UL13 deletion mutant virus (Delta UL13). After treatment with phosphatase, the electrophoretic mobility of the Us3 isoforms from cells infected with wild-type virus changed, with one isoform migrating as fast as one of the Us3 isoforms from Delta UL13-infected cells. (ii) A recombinant protein containing a domain of Us3 was phosphorylated by UL13 in vitro. (iii) The phenotype of Delta UL13 resembles that of a recombinant virus lacking the Us3 gene (Delta Us3) with respect to localization of the viral envelopment factors UL34 and UL31, whose localization has been shown to be regulated by Us3. UL34 and UL31 are localized in a smooth pattern throughout the nuclei of cells infected with wild-type virus, whereas their localization in Delta UL13- and Delta Us3-infected cells appeared as nuclear punctate patterns. These results indicate that UL13 phosphorylates Us3 in infected cells and regulates UL34 and UL31 localization, either by phosphorylating Us3 or by a Us3-independent mechanism.