The Epstein-Barr virus-encoded LMP2A and LMP2B proteins promote epithelial cell spreading and motility
The Epstein-Barr virus-encoded LMP2A and LMP2B proteins promote epithelial cell spreading and motility
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DOI：
10.1128/jvi.79.3.1789-1802.2005
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发表时间：
2005-02-01
影响因子：
5.4
通讯作者：
Dawson, CW
中科院分区：
文献类型：
--
作者：
Allen, MD;Young, LS;Dawson, CW
潜伏膜蛋白 LMP2A 和 LMP2B 在 Epstein Barr 病毒 (EBV) 相关肿瘤中的频繁表达表明这些蛋白在 EBV 诱导的上皮细胞生长转化中发挥作用。 LMP2A和LMP2B的表达对单层培养中的鳞状上皮细胞的形态没有影响，但它们的表达与在细胞外基质上扩散和迁移的能力增加相关。尽管 LMP2A 和 LMP2B 促进细胞扩散和运动的机制尚不清楚，但选择性药理学抑制剂的使用已确定酪氨酸激酶在该表型中的作用，但排除了磷脂酰肌醇 3-激酶、细胞外信号调节激酶/丝裂原激活蛋白激酶和蛋白激酶 C 的作用。 LMP2B 诱导的表型与 LMP2A 的表型几乎没有区别，这表明除了胞质氨基末端之外，LMP2 蛋白的区域也能够在上皮细胞中诱导表型效应。因此，LMP2B 可能直接参与信号通路来影响上皮细胞行为，例如细胞粘附和运动，而不是调节 LMP2A 的活性。
The frequent expression of latent membrane proteins LMP2A and LMP2B in Epstein Barr virus (EBV)associated tumors suggests that these proteins play a role in EBV-induced epithelial cell growth transformation. Expression of LMP2A and LMP2B had no effect on the morphology of squamous epithelial cells in monolayer culture, but their expression was associated with an increased capacity to spread and migrate on extracellular matrix. Although the mechanisms by which LMP2A and LMP2B promote cell spreading and motility are unclear, the use of selective pharmacological inhibitors has established a role for tyrosine kinases in this phenotype but ruled out contributions of phosphatidylinositol 3-kinase, extracellular signal-regulated kinase/mitogen-activated protein kinase, and protein kinase C. The ability of LMP2B to induce a phenotype that is virtually indistinguishable from that of LMP2A suggests that regions of the LMP2 protein in addition to the cytosolic amino terminus are capable of inducing phenotypic effects in epithelial cells. Thus, rather than serving to modulate the activity of LMP2A, LMP2B may directly engage signaling pathways to influence epithelial cell behavior such as cell adhesion and motility.