PUBLICATION

Angiomotin-like2 Gene (amotl2) Is Required for Migration and Proliferation of Endothelial Cells during Angiogenesis

Authors
Wang, Y., Li, Z., Xu, P., Huang, L., Tong, J., Huang, H., and Meng, A.
ID
ZDB-PUB-111011-1
Date
2011
Source
The Journal of biological chemistry   286(47): 41095-104 (Journal)
Registered Authors
Meng, Anming, Tong, Jingyuan, Xu, Pengfei
Keywords
angiogenesis, embryo, endothelial cell, MAP kinases (MAPKs), zebrafish angiomotion-like2
MeSH Terms
  • Amino Acid Motifs
  • Animals
  • Blood Vessels/cytology
  • Blood Vessels/physiology
  • Carrier Proteins/chemistry
  • Carrier Proteins/genetics
  • Carrier Proteins/metabolism*
  • Cell Movement*/genetics
  • Cell Polarity/genetics
  • Cell Proliferation
  • Endothelial Cells/cytology*
  • Endothelial Cells/metabolism*
  • Enzyme Activation/genetics
  • Extracellular Signal-Regulated MAP Kinases/metabolism
  • Gene Knockdown Techniques
  • HEK293 Cells
  • Human Umbilical Vein Endothelial Cells/cytology
  • Human Umbilical Vein Endothelial Cells/metabolism
  • Humans
  • Membrane Proteins/chemistry
  • Membrane Proteins/deficiency
  • Membrane Proteins/genetics
  • Membrane Proteins/metabolism*
  • Mice
  • Neovascularization, Physiologic*/genetics
  • Phosphorylation/genetics
  • Protein-Tyrosine Kinases/metabolism
  • Signal Transduction/genetics
  • Tyrosine/metabolism
  • Zebrafish/embryology
  • Zebrafish Proteins/chemistry
  • Zebrafish Proteins/deficiency
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
  • src-Family Kinases
PubMed
21937427 Full text @ J. Biol. Chem.
Abstract
Angiogenesis involves sprouting, migration and proliferation of endothelial cells. angiomotin-like2 (amotl2) has been found to express in blood vessels in zebrafish embryos, but its function in angiogenesis and underlying mechanisms remain unknown. In this study, we demonstrate that knockdown of amotl2 in zebrafish Tg(fli1:EGFP)y1 and Tg(fli1:nEGFP)y7 transgenic embryos impairs the intersegmental vessel (ISV) growth and suppresses proliferation of endothelial cells. Transplantation experiments indicate that function of amotl2 in ISV growth is cell-autonomous. AMOTL2 knockdown in cultured human umbilical vein endothelial cells (HUVECs) also inhibits cell proliferation and migration and disrupts cell polarity, ultimately interrupting the formation of vascular tube-like structures. Amotl2 promotes MAPK/ERK activation via c-Src, which is dependent on phosphorylation of tyrosine residue at position 103 but independent of C-terminal PDZ-binding domain. Taking together, our data indicate that Amotl2 plays a pivotal role in polarity, migration and proliferation of angiogenic endothelial cells.
Genes / Markers
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Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
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Mapping