Cell Migration Is Regulated by Platelet-Derived Growth Factor Receptor Endocytosis
Cell Migration Is Regulated by Platelet-Derived Growth Factor Receptor Endocytosis
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DOI：
10.1128/mcb.00015-09
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发表时间：
2009-08-15
影响因子：
5.3
通讯作者：
Yajnik, Vijay
中科院分区：
文献类型：
--
作者：
Kawada, Kenji;Upadhyay, Geeta;Yajnik, Vijay
细胞迁移需要检测细胞外刺激并将其转化为细胞内信号的时空过程。血小板衍生生长因子（PDGF）受体是成纤维细胞的细胞表面受体，在PDGF的作用下调节增殖和趋化。PDGF信号如何通过受体准确地传递到细胞中是一个尚未解决的问题。在这里，我们报道了一种新的细胞内信号通路，Rac1鸟嘌呤交换因子DOCK4和Dynamin通过PDGF受体内吞作用调节细胞迁移。通过一系列的生化和显微镜技术，我们发现Grb2在PDGF受体、DOCK4和Dynamin之间三元复合物的形成中起着衔接蛋白的作用，该复合物形成于细胞的前缘。我们发现这种三元复合物通过促进PDGF受体内吞作用和细胞膜上的Rac1激活来调节PDGF依赖的细胞迁移。本研究揭示了PDGF受体内吞作用调控细胞迁移的新机制。
Cell migration requires spatial and temporal processes that detect and transfer extracellular stimuli into intracellular signals. The platelet-derived growth factor (PDGF) receptor is a cell surface receptor on fibroblasts that regulates proliferation and chemotaxis in response to PDGF. How the PDGF signal is transmitted accurately through the receptor into cells is an unresolved question. Here, we report a new intracellular signaling pathway by which DOCK4, a Rac1 guanine exchange factor, and Dynamin regulate cell migration by PDGF receptor endocytosis. We showed by a series of biochemical and microscopy techniques that Grb2 serves as an adaptor protein in the formation of a ternary complex between the PDGF receptor, DOCK4, and Dynamin, which is formed at the leading edge of cells. We found that this ternary complex regulates PDGF-dependent cell migration by promoting PDGF receptor endocytosis and Rac1 activation at the cell membrane. This study revealed a new mechanism by which cell migration is regulated by PDGF receptor endocytosis.