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
-
- Chlorocebus aethiops
- Intercellular Signaling Peptides and Proteins/genetics
- Intercellular Signaling Peptides and Proteins/metabolism*
- Actins/genetics
- Actins/metabolism*
- Animals
- COS Cells
- Amino Acid Motifs
- Cell Movement/physiology*
- Human Umbilical Vein Endothelial Cells
- Zebrafish
- Tumor Suppressor Proteins/genetics
- Tumor Suppressor Proteins/metabolism*
- Embryo, Nonmammalian/cytology
- Embryo, Nonmammalian/metabolism*
- Humans
- HEK293 Cells
- Membrane Proteins/genetics
- Membrane Proteins/metabolism*
- Zebrafish Proteins/genetics
- Zebrafish Proteins/metabolism
- Focal Adhesions/genetics
- Focal Adhesions/metabolism
- Protein Serine-Threonine Kinases/genetics
- Protein Serine-Threonine Kinases/metabolism*
- Neovascularization, Physiologic/physiology*
- 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.