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Cell Migration Is Regulated by Platelet-Derived Growth Factor Receptor Endocytosis

机译:细胞迁移受血小板衍生生长因子受体胞吞作用的调节

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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.
机译:细胞迁移需要空间和时间过程,以检测并将细胞外刺激转移到细胞内信号。血小板衍生的生长因子(PDGF)受体是成纤维细胞上的细胞表面受体,可响应PDGF调节增殖和趋化性。 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,我们报告了一个新的细胞内信号通路,DOCK4,Rac1鸟嘌呤交换因子和Dynamin通过PDGF受体胞吞作用调节细胞迁移。我们通过一系列的生化和显微镜技术表明,Grb2在PDGF受体,DOCK4和Dynamin之间形成三元复合物时充当衔接蛋白,后者在细胞的前缘形成。我们发现,这种三元复合物通过促进PDGF受体的内吞作用和在细胞膜上的Rac1激活来调节PDGF依赖性细胞的迁移。这项研究揭示了PDGF受体胞吞作用调节细胞迁移的新机制。

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