Phosphorylation of angiomotin by Lats1/2 kinases inhibits F-actin binding, cell migration, and angiogenesis.
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.
Mesh Terms:
Actins, Amino Acid Motifs, Animals, COS Cells, Cell Movement, Cercopithecus aethiops, Embryo, Nonmammalian, Focal Adhesions, HEK293 Cells, Human Umbilical Vein Endothelial Cells, Humans, Intercellular Signaling Peptides and Proteins, Membrane Proteins, Neovascularization, Physiologic, Protein-Serine-Threonine Kinases, Tumor Suppressor Proteins, Zebrafish, Zebrafish Proteins
Actins, Amino Acid Motifs, Animals, COS Cells, Cell Movement, Cercopithecus aethiops, Embryo, Nonmammalian, Focal Adhesions, HEK293 Cells, Human Umbilical Vein Endothelial Cells, Humans, Intercellular Signaling Peptides and Proteins, Membrane Proteins, Neovascularization, Physiologic, Protein-Serine-Threonine Kinases, Tumor Suppressor Proteins, Zebrafish, Zebrafish Proteins
J. Biol. Chem.
Date: Nov. 22, 2013
PubMed ID: 24106267
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