Epstein-Barr virus-encoded LMP1 regulates epithelial cell motility and invasion via the ERK-MAPK pathway
Epstein-Barr virus-encoded LMP1 regulates epithelial cell motility and invasion via the ERK-MAPK pathway
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DOI：
10.1128/jvi.01888-07
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发表时间：
2008-04-01
影响因子：
5.4
通讯作者：
Young, Lawrence S.
中科院分区：
文献类型：
--
作者：
Dawson, Christopher W.;Laverick, Louise;Young, Lawrence S.
eb病毒（EBV）潜伏膜蛋白1 （LMP1）是一种致癌蛋白，先前已被证明参与nf - κ B、应激激活MAP激酶、磷脂酰肌醇3-激酶（PI 3-激酶）和细胞外调节激酶(ERK)-MAPK途径。在这项研究中，我们证明LMP1通过典型的Raf-MEK-ERK-MAPK途径激活上皮细胞中的ERK-MAPK，但以ras独立的方式激活。与先前的研究结果一致（B. a . Mainou， D. N. Everly, Jr.，和N. Raab-Traub， J. Virol. 81:9680-9692, 2007），我们表明LMP1激活ERK-MAPK的能力映射到其CTAR1结构域，该结构域先前与PI 3-激酶激活有关。ERK-MAPK在lmp1诱导的上皮细胞运动中的作用被确定，因为与lmp1阴性细胞相比，表达lmp1的细胞表现出更高的触致迁移率。这些数据暗示了ERK-MAPK通路在LMP1诱导的转化相关效应中，表明该通路可能通过其促进细胞运动和增强上皮细胞侵袭性的能力而促进LMP1的致癌性。
The Epstein-Barr virus (EBV) latent membrane protein 1 (LMP1) is an oncogenic protein which has previously been shown to engage the NF-kappa B, stress-activated MAP kinase, phosphatidylinositol 3-kinase (PI 3-kinase), and extracellular-regulated kinase (ERK)-MAPK pathways. In this study, we demonstrate that LMP1 activates ERK-MAPK in epithelial cells via the canonical Raf-MEK-ERK-MAPK pathway but in a Ras-independent manner. In agreement with the results of a previous study (B. A. Mainou, D. N. Everly, Jr., and N. Raab-Traub, J. Virol. 81:9680-9692, 2007), we show that the ability of LMP1 to activate ERK-MAPK mapped to its CTAR1 domain, the TRAF binding domain previously implicated in PI 3-kinase activation. A role for ERK-MAPK in LMP1-induced epithelial cell motility was identified, as LMP1-expressing cells displayed increased rates of haptotactic migration compared to those of LMP1-negative cells. These data implicate the ERK-MAPK pathway in LMP1-induced effects associated with transformation, suggesting that this pathway may contribute to the oncogenicity of LMP1 through its ability to promote cell motility and to enhance the invasive properties of epithelial cells.