Ephrin-B2 regulates endothelial cell morphology and motility independently of Eph-receptor binding
Ephrin-B2 regulates endothelial cell morphology and motility independently of Eph-receptor binding
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DOI：
10.1242/jcs.061903
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发表时间：
2010-04-15
影响因子：
4
通讯作者：
Nobes, Catherine D.
中科院分区：
文献类型：
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作者：
Bochenek, Magdalena L.;Dickinson, Sarah;Nobes, Catherine D.
跨膜蛋白肝配蛋白-B2调节血管生成，即通过内皮发芽、增殖和重塑过程形成新血管。除了在胚胎脉管系统中的重要作用之外，肝配蛋白-B2表达在成人中在新血管形成部位（如肿瘤和伤口）上调。已知肝配蛋白结合相邻细胞上的Eph受体家族酪氨酸激酶，并触发两种相互作用分子下游的双向信号转导。在这里，我们表明，肝配蛋白-B2动态调节运动和细胞形态的分离内皮细胞。即使在没有Eph-受体结合的情况下，肝配蛋白-B2刺激肌动球蛋白依赖性细胞收缩和扩散事件之间的重复循环，这需要C-末端PDZ基序的存在。我们的研究结果表明，ephrin-B2是一个有效的调节内皮细胞的行为，并表明，控制细胞迁移和血管生成的ephrins可能涉及受体依赖性和受体无关的活动。
The transmembrane protein ephrin-B2 regulates angiogenesis, i.e. the formation of new blood vessels through endothelial sprouting, proliferation and remodeling processes. In addition to essential roles in the embryonic vasculature, ephrin-B2 expression is upregulated in the adult at sites of neovascularization, such as tumors and wounds. Ephrins are known to bind Eph receptor family tyrosine kinases on neighboring cells and trigger bidirectional signal transduction downstream of both interacting molecules. Here we show that ephrin-B2 dynamically modulates the motility and cellular morphology of isolated endothelial cells. Even in the absence of Eph-receptor binding, ephrin-B2 stimulates repeated cycling between actomyosin-dependent cell contraction and spreading episodes, which requires the presence of the C-terminal PDZ motif. Our results show that ephrin-B2 is a potent regulator of endothelial cell behavior, and indicate that the control of cell migration and angiogenesis by ephrins might involve both receptor-dependent and receptor-independent activities.