Phosphorylation of Angiomotin by Lats1/2 Kinases Inhibits F-actin Binding, Cell Migration, and Angiogenesis

作者：Xiaoming Dai, Peilu She, Fangtao Chi, Ying Feng, Huan Liu, Da‐Qing Jin, Yiqiang Zhao, Xiaocan Guo, Dandan Jiang, Kun‐Liang Guan, Tao P. Zhong, Bin Zhao · 发表于：Journal of Biological Chemistry · 年份：2013 · DOI：10.1074/jbc.m113.518019 · 被引用次数：157 · 研究领域：Hippo pathway signaling and YAP/TAZ

The Hippo tumor suppressor pathway plays important roles in organ size control through Lats1/2 mediated phosphorylation of the YAP/TAZ transcription co-activators. However, YAP/TAZ independent functions of the Hippo pathway are largely unknown. Here we report a novel role of the Hippo pathway in angiogenesis. Angiomotin p130 isoform (AMOTp130) is phosphorylated on a conserved HXRXXS motif by Lats1/2 downstream of GPCR signaling. Phosphorylation disrupts AMOT interaction with F-actin and correlates with reduced F-actin stress fibers and focal adhesions. Furthermore, phosphorylation of AMOT by Lats1/2 inhibits endothelial cell migration in vitro and angiogenesis in zebrafish embryos in vivo. Thus AMOT is a direct substrate of Lats1/2 mediating functions of the Hippo pathway in endothelial cell migration and angiogenesis.