PUBLICATION

Phosphorylation of angiomotin by Lats1/2 kinases inhibits F-actin binding, cell migration and angiogenesis

Authors
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.
ID
ZDB-PUB-131112-15
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
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Humans
  • HEK293 Cells
  • Protein Serine-Threonine Kinases/genetics
  • Protein Serine-Threonine Kinases/metabolism*
  • Actins/genetics
  • Actins/metabolism*
  • Amino Acid Motifs
  • Focal Adhesions/genetics
  • Focal Adhesions/metabolism
  • Neovascularization, Physiologic/physiology*
  • Embryo, Nonmammalian/cytology
  • Embryo, Nonmammalian/metabolism*
  • Chlorocebus aethiops
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism
  • Animals
  • Cell Movement/physiology*
  • Zebrafish
  • Tumor Suppressor Proteins/genetics
  • Tumor Suppressor Proteins/metabolism*
  • COS Cells
  • Intercellular Signaling Peptides and Proteins/genetics
  • Intercellular Signaling Peptides and Proteins/metabolism*
  • Human Umbilical Vein Endothelial Cells
PubMed
24106267 Full text @ J. Biol. Chem.
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.

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