Localization of ERK/MAP kinase is regulated by the alphaherpesvirus tegument protein Us2.
Localization of ERK/MAP kinase is regulated by the alphaherpesvirus tegument protein Us2.
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ERK/MAP 激酶的定位受 α 疱疹病毒外皮蛋白 Us2 调节。
DOI：
10.1128/jvi.00592-06
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发表时间：
2006
期刊：
影响因子：
--
通讯作者：
Banfield,BruceW
中科院分区：
文献类型：
--
作者：
Lyman,MathewG;Randall,JessicaA;Calton,ChristineM;Banfield,BruceW
许多不同的病毒在感染过程中激活细胞外信号调节蛋白(ERK)/丝裂原活化蛋白(MAP)信号通路，并需要ERK激活才能有效地执行其复制程序。尽管有这些发现，但还没有发现直接调节ERK活性的病毒编码蛋白。为了确定一种保守的甲型疱疹病毒结构蛋白US2的功能，我们从NIH 3T3细胞中筛选出一个酵母双杂交文库，并鉴定ERK是一种与US2相互作用的蛋白。我们的研究表明，在病毒感染的细胞中，US2与ERK结合，介导ERK进入病毒粒子，并抑制ERK核底物的激活。US2与ERK的结合导致ERK滞留在质膜和核周的囊泡室，从而将ERK排除在细胞核之外。US2可以与激活的ERK结合，数据表明US2不抑制ERK的酶活性。用ERK激活的特异性抑制剂U0126处理细胞后，病毒从受感染细胞中释放的时间显著延迟，而删除US2的病毒比亲本和修复的病毒更明显，这表明ERK和US2的活性都是有效复制病毒所必需的。这项研究强调了病毒激活ERK的另一个复杂性，即活性ERK的定位可以被病毒编码的蛋白质改变。
Many different viruses activate the extracellular signal-regulated kinase (ERK)/mitogen-activated protein (MAP) kinase signaling pathway during infection and require ERK activation for the efficient execution of their replication programs. Despite these findings, no virus-encoded proteins have been identified that directly modulate ERK activities. In an effort to determine the function of a conserved alphaherpesvirus structural protein called Us2, we screened a yeast two-hybrid library derived from NIH 3T3 cells and identified ERK as a Us2-interacting protein. Our studies indicate that Us2 binds to ERK in virus-infected cells, mediates the incorporation of ERK into the virion, and inhibits the activation of ERK nuclear substrates. The association of Us2 with ERK leads to the sequestration of ERK at the plasma membrane and to a perinuclear vesicular compartment, thereby keeping ERK out of the nucleus. Us2 can bind to activated ERK, and the data suggest that Us2 does not inhibit ERK enzymatic activity. The treatment of cells with U0126, a specific inhibitor of ERK activation, resulted in a substantial delay in the release of virus from infected cells that was more pronounced with a virus deleted for Us2 than with parental and repaired strains, suggesting that both ERK and Us2 activities are required for efficient virus replication. This study highlights an additional complexity to the activation of ERK by viruses, namely, that localization of active ERK can be altered by virus-encoded proteins.
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影响因子：
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作者：
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DOI：
--
发表时间：
2001
期刊：
影响因子：
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作者：
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DOI：
--
发表时间：
1984
期刊：
影响因子：
--
作者：
S. Herrmann;B. Heppner;H. Ludwig
通讯作者：
H. Ludwig
影响因子：
4.8
作者：
Hemonnot, B;Cartier, C;Briant, L
通讯作者：
Briant, L