Papillomavirus virus-like particles activate the PI3-kinase pathway via alpha-6 beta-4 integrin upon binding
Papillomavirus virus-like particles activate the PI3-kinase pathway via alpha-6 beta-4 integrin upon binding
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DOI：
10.1016/j.virol.2006.05.002
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发表时间：
2006-09-01
期刊：
影响因子：
3.7
通讯作者：
McMillan, Nigel A. J.
中科院分区：
文献类型：
--
作者：
Fothergill, Thomas;McMillan, Nigel A. J.
我们以前已经表明，人乳头瘤病毒病毒样颗粒（VLP）能够激活Ras/MAP激酶通路。Ras还可以通过PI 3-激酶引发抗凋亡信号，因此我们进一步研究了这一点。在这里，我们表明来自HPV 6 b、18、31、35型和BPV 1的VLP的结合导致PI 3-激酶的活化。通过L1或L1/L2 VLP实现激活，并且依赖于VLP-细胞相互作用和病毒颗粒的正确构象。VLP诱导的PI 3-激酶活性导致Akt的有效下游信号传导和随后的FKHR和GSK 3 β磷酸化。我们还提出证据表明，PV信号通过α 6 β 4整合素激活。这些数据表明，乳头状瘤病毒使用一个共同的受体，能够通过信号Ras。Ras/MAP激酶和PI 3-激酶途径的联合激活可能通过增加细胞数量和产生更有利于感染的环境而对病毒有益。(c)2006年爱思唯尔公司All rights reserved.
We have previously shown that human papillomavirus virus-like particles (VLPs) are able to activate the Ras/MAP kinase pathway. Ras can also elicit an anti-apoptotic signal via PI3-kinase so we investigated this further. Here we show that binding of VLPs from HPV types 6b, 18, 3 1, 35 and BPV1 results in activation of PI3-kinase. Activation was achieved by either L1 or L1/L2 VLPs and was dependent on both VLP-cell interaction and correct conformation of the virus particle. VLP-induced PI3-kinase activity resulted in efficient downstream signaling to Akt and consequent phosphorylation of FKHR and GSK3 beta. We also present evidence that PV signaling is activated via the alpha 6 beta 4 integrin. These data suggest that papillomaviruses use a common receptor that is able to signal through to Ras. Combined activation of the Ras/MAP kinase and PI3-kinase pathways may be beneficial for the virus by increasing cell numbers and producing an environment more conducive to infection. (c) 2006 Elsevier Inc. All rights reserved.