J Biol Chem. 2013 Oct 8. [Epub ahead of print]
Xiaoming Dai, Peilu She, Fangtao Chi, Ying Feng, Huan Liu, Daqing Jin, Yiqiang Zhao,Xiaocan Guo, Dandan Jiang, Kun-Liang Guan, Tao P. Zhong, Bin Zhao
Abstract
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 Lats1/2inhibits endothelial cellmigration 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 cellmigration and angiogenesis.
