生物
血管生成
细胞生物学
血管内皮生长因子受体
信号转导
河马信号通路
血管内皮生长因子
肌动蛋白细胞骨架
血管内皮生长因子A
效应器
细胞骨架
癌症研究
细胞
遗传学
作者
Xiaohong Wang,Aïda Valls,Géza Schermann,Shao‐Yao Ying,Iván M. Moya,Laura C. Castro,Severino Urban,Gergely Solecki,Frank Winkler,Lars Riedemann,Rakesh K. Jain,Massimiliano Mazzone,Thomas Schmidt,Tamás Fischer,Georg Halder,Carmen Ruiz de Almodóvar
标识
DOI:10.1016/j.devcel.2017.08.002
摘要
Vascular endothelial growth factor (VEGF) is a major driver of blood vessel formation. However, the signal transduction pathways culminating in the biological consequences of VEGF signaling are only partially understood. Here, we show that the Hippo pathway effectors YAP and TAZ work as crucial signal transducers to mediate VEGF-VEGFR2 signaling during angiogenesis. We demonstrate that YAP/TAZ are essential for vascular development as endothelium-specific deletion of YAP/TAZ leads to impaired vascularization and embryonic lethality. Mechanistically, we show that VEGF activates YAP/TAZ via its effects on actin cytoskeleton and that activated YAP/TAZ induce a transcriptional program to further control cytoskeleton dynamics and thus establish a feedforward loop that ensures a proper angiogenic response. Lack of YAP/TAZ also results in altered cellular distribution of VEGFR2 due to trafficking defects from the Golgi apparatus to the plasma membrane. Altogether, our study identifies YAP/TAZ as central mediators of VEGF signaling and therefore as important regulators of angiogenesis.
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