Cellular serine/threonine phosphatase activity during human cytomegalovirus infection
Cellular serine/threonine phosphatase activity during human cytomegalovirus infection
复制标题
DOI：
10.1016/j.virol.2008.07.028
复制
发表时间：
2008-10-25
期刊：
影响因子：
3.7
通讯作者：
Geballe, Adam P.
中科院分区：
文献类型：
--
作者：
Hakki, Morgan;Geballe, Adam P.
虽然细胞和病毒激酶在 HCMV 复制中的重要性已被证明，但人们对细胞磷酸酶的活性知之甚少。我们进行了一系列实验，旨在研究 HCMV 感染对细胞丝氨酸/苏氨酸磷酸酶活性的影响。我们发现两种主要细胞丝氨酸/苏氨酸磷酸酶 PP1 和 PP2A 的丰度在 HCMV 感染期间增加。这与 HCMV 感染细胞中苏氨酸磷酸酶活性的增加有关。 HCMV 感染赋予了对磷酸酶抑制剂花萼蛋白 A (CA) 和冈田酸在整体蛋白质过度磷酸化和蛋白质合成停止方面的作用的抵抗力。高浓度的 CA 可以克服 HCMV 感染的保护作用，这表明细胞磷酸酶活性是 HCMV 感染期间关键细胞过程所必需的。具体来说，在 HCMV 感染期间，需要磷酸酶活性来限制磷酸化 eIF2 α 的积累，而不是限制磷酸化 PKR 的积累。 (C) 2008 Elsevier Inc，保留所有权利。
While the importance of cellular and viral kinases in HCMV replication has been demonstrated, relatively little is known about the activity of cellular phosphatases. We conducted a series of experiments designed to investigate the effect of HCMV infection on cellular serine/threonine phosphatase activity. We found that the abundance of two major cellular serine/threonine phosphatases, PP1 and PP2A, increases during HCMV infection. This was associated with an increase in threonine phosphatase activity in HCMV-infected cells. HCMV infection conferred resistance to the effects of the phosphatase inhibitors calyculin A (CA) and okadaic acid with regards to global protein hyperphosphorylation and the shutoff of protein synthesis. The protective effect of HCMV infection could be overcome at a high concentration of CA, suggesting that cellular phosphatase activity is required for critical cellular processes during HCMV infection. Specifically, phosphatase activity was required to limit the accumulation of phospho-eIF2 alpha, but not phospho-PKR, during HCMV infection. (C) 2008 Elsevier Inc, All rights reserved.