Src-dependent ezrin phosphorylation in adhesion-mediated signaling
Src-dependent ezrin phosphorylation in adhesion-mediated signaling
复制标题
DOI：
10.1091/mbc.e04-08-0721
复制
发表时间：
2005-03-01
影响因子：
3.3
通讯作者：
Arpin, M
中科院分区：
文献类型：
--
作者：
Srivastava, J;Elliott, BE;Arpin, M
埃兹蛋白除了在细胞膜和肌动蛋白细胞骨架之间提供调节性连接外，还参与信号转导途径。在这里，我们描述了ezrin Y145 F突变体的表达通过抑制FAK激活来延迟上皮细胞在纤连蛋白上的扩散。通过过表达具有催化功能的Src来挽救扩散中的缺陷。我们证明，ezrin Y145是磷酸化的A431细胞刺激表皮生长因子（EGF）和V-Src转化细胞。此外，在缺乏Src的细胞中，SYF-/-成纤维细胞，ezrin Y145磷酸化只能在引入活性形式的Src后检测到。Ezrin在Y145的磷酸化需要Src SH 2结构域与Ezrin的预先结合。我们的研究结果进一步表明，Src活性影响其结合ezrin和Src介导的Y145磷酸化的正反馈机制是隐含的。有趣的是，表达ezrin Y145 F的细胞在3D胶原凝胶中培养时不增殖。总的来说，我们的研究结果表明，在上皮细胞的粘附介导的事件Src依赖埃兹蛋白磷酸化的关键信号输入。
In addition to providing a regulated linkage between the membrane and the actin cytoskeleton, ezrin participates in signal transduction pathways. Here we describe that expression of the ezrin Y145F mutant delays epithelial cell spreading on fibronectin by inhibiting events leading to FAK activation. The defect in spreading was rescued by the overexpression of catalytically functional Src. We demonstrate that ezrin Y145 is phosphorylated in A431 cells stimulated with epidermal growth factor (EGF) and in v-Src-transformed cells. Moreover in cells devoid of Src, SYF-/- fibroblasts, ezrin Y145 phosphorylation could only be detected upon the introduction of an active form of Src. The phosphorylation of ezrin at Y145 required prior binding of the Src SH2 domain to ezrin. Our results further show that Src activity influences its binding to ezrin and a positive feedback mechanism for Src-mediated Y145 phosphorylation is implied. Interestingly, cells expressing ezrin Y145F did not proliferate when cultured in a 3D collagen gel. Collectively, our results demonstrate a key signaling input of Src-dependent ezrin phosphorylation in adhesion-mediated events in epithelial cells.