Dai, X., She, P., Chi, F., Feng, Y., Liu, H., Jin, D., Zhao, Y., Guo, X., Jiang, D., Guan, K.L., Zhong, T.P., and Zhao, B. (2013) Phosphorylation of angiomotin by Lats1/2 kinases inhibits F-actin binding, cell migration and angiogenesis. The Journal of biological chemistry. 288(47):34041-51.
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 Lats1/2 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.
