Division of Molecular Medical Biochemistry, Department of Biochemistry and Molecular Biology, Shiga University of Medical Science, Otsu, Shiga 520-2192, Japan.
Department of Molecular Biosciences, Faculty of Life Sciences, Kyoto Sangyo University, Kyoto 603-8555, Japan.
Int J Mol Sci. 2018 Apr 16;19(4):1203. doi: 10.3390/ijms19041203.
Vascular endothelial growth factors (VEGFs) include five molecules (VEGF-A, -B, -C, -D, and placental growth factor), and have various roles that crucially regulate cellular functions in many kinds of cells and tissues. Intracellular signal transduction induced by VEGFs has been extensively studied and is usually initiated by their binding to two classes of transmembrane receptors: receptor tyrosine kinase VEGF receptors (VEGF receptor-1, -2 and -3) and neuropilins (NRP1 and NRP2). In addition to many established results reported by other research groups, we have previously identified small G proteins, especially Ras homologue gene (Rho) and Ras-related protein (Rap), as important mediators of VEGF-A-stimulated signaling in cancer cells as well as endothelial cells. This review article describes the VEGF-A-induced signaling pathways underlying diverse cellular functions, including cell proliferation, migration, and angiogenesis, and the involvement of Rho, Rap, and their related molecules in these pathways.
血管内皮生长因子（VEGFs）包括五种分子（VEGF-A、-B、-C、-D 和胎盘生长因子），具有多种作用，这些作用对于调节多种细胞和组织的细胞功能至关重要。VEGFs 诱导的细胞内信号转导已经得到了广泛的研究，通常是由它们与两类跨膜受体结合而引发的：受体酪氨酸激酶 VEGFR（VEGF 受体-1、-2 和-3）和神经毡蛋白（NRP1 和 NRP2）。除了其他研究小组报告的许多已确立的结果外，我们之前还确定了小 G 蛋白，特别是 Ras 同源基因（Rho）和 Ras 相关蛋白（Rap），作为 VEGF-A 刺激癌细胞和内皮细胞信号转导的重要介质。本文综述了 VEGF-A 诱导的信号通路，这些通路涉及多种细胞功能，包括细胞增殖、迁移和血管生成，以及 Rho、Rap 及其相关分子在这些通路中的作用。
