Department of Virology, Parasitology, and Immunology, Faculty of Veterinary Medicine, Ghent University, Salisburylaan 133, 9820 Merelbeke, Belgium.
Virus Res. 2011 Jan;155(1):376-80. doi: 10.1016/j.virusres.2010.11.003. Epub 2010 Nov 18.
The alphaherpesvirus US3 kinase is a conserved multifunctional serine/threonine kinase that plays a role in several processes, including modulation of the actin cytoskeleton, egress of virus particles from the nucleus and inhibition of apoptosis. However, the mechanisms used by the US3 protein to exert its functions remain poorly understood. Recently, we identified the group A p21-activated kinases PAK1 and PAK2 as important effectors in the US3-mediated cytoskeletal rearrangements. Here, we investigated if group A PAKs are also involved in the anti-apoptotic properties of US3. Infection experiments using a group A PAK inhibitor pointed at a moderate role for group A PAKs in the anti-apoptotic properties of US3. Furthermore, infection assays using wild type and US3null PRV in wild type MEF, PAK1(-/-) MEF and PAK2(-/-) MEF indicated that PAK2 does not play a role in US3-mediated inhibition of apoptosis during infection, whereas PAK1 plays a significant, yet limited role. Experiments in US3-transfected MEF using staurosporine as apoptosis trigger confirmed these observations. These results show that PAK1 plays a significant, yet limited, role in the anti-apoptotic activity of US3.
α疱疹病毒 US3 激酶是一种保守的多功能丝氨酸/苏氨酸激酶，在包括肌动蛋白细胞骨架的调节、病毒粒子从核内的出芽以及凋亡的抑制等多个过程中发挥作用。然而，US3 蛋白发挥其功能所使用的机制仍知之甚少。最近，我们鉴定出 PAK1 和 PAK2 作为 US3 介导的细胞骨架重排中的重要效应物。在这里，我们研究了 PAK1 是否也参与了 US3 的抗凋亡特性。使用 PAK1 抑制剂的感染实验表明 PAK1 在 US3 的抗凋亡特性中起中度作用。此外，使用野生型和 US3null PRV 在野生型 MEF、PAK1(-/-) MEF 和 PAK2(-/-) MEF 中的感染实验表明，PAK2 在感染过程中不参与 US3 介导的凋亡抑制，而 PAK1 则起显著但有限的作用。使用 staurosporine 作为凋亡触发剂的 US3 转染 MEF 实验证实了这些观察结果。这些结果表明 PAK1 在 US3 的抗凋亡活性中起显著但有限的作用。
