ZFIN ID: ZDB-PUB-131112-15
Phosphorylation of angiomotin by Lats1/2 kinases inhibits F-actin binding, cell migration and angiogenesis
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.
Date: 2013
Source: The Journal of biological chemistry   288(47): 34041-51 (Journal)
Registered Authors: Zhong, Tao P.
Keywords: actin, angiogenesis cell migration, protein kinases, protein phosphorylation, lats, amot, protein kinase, the Hippo pathway
MeSH Terms:
  • Actins/genetics
  • Actins/metabolism*
  • Amino Acid Motifs
  • Animals
  • COS Cells
  • Cell Movement/physiology*
  • Chlorocebus aethiops
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism*
  • Focal Adhesions/genetics
  • Focal Adhesions/metabolism
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells
  • Humans
  • Intercellular Signaling Peptides and Proteins/genetics
  • Intercellular Signaling Peptides and Proteins/metabolism*
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Neovascularization, Physiologic/physiology*
  • Protein-Serine-Threonine Kinases/genetics
  • Protein-Serine-Threonine Kinases/metabolism*
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/metabolism*
  • Zebrafish
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
PubMed: 24106267 Full text @ J. Biol. Chem.

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.