header logo image header logo text
Downloads Login
General Information
ZFIN ID: ZDB-PUB-050930-4
Cooperative interaction of Angiopoietin-like proteins 1 and 2 in zebrafish vascular development
Kubota, Y., Oike, Y., Satoh, S., Tabata, Y., Niikura, Y., Morisada, T., Akao, M., Urano, T., Ito, Y., Miyamoto, T., Nagai, N., Koh, G.Y., Watanabe, S., and Suda, T.
Date: 2005
Source: Proceedings of the National Academy of Sciences of the United States of America   102(38): 13502-13507 (Journal)
Registered Authors: Watanabe, Sumiko
Keywords: none
MeSH Terms:
  • Angiopoietins/genetics
  • Angiopoietins/metabolism*
  • Animals
  • Apoptosis/drug effects
  • Apoptosis/physiology*
  • Blood Vessels/cytology
  • Blood Vessels/embryology*
  • Endothelial Cells/cytology
  • Endothelial Cells/metabolism*
  • Gene Silencing
  • Intercellular Signaling Peptides and Proteins/metabolism*
  • Oligodeoxyribonucleotides, Antisense/administration & dosage
  • Oligodeoxyribonucleotides, Antisense/genetics
  • Phosphatidylinositol 3-Kinases/metabolism
  • Protein-Serine-Threonine Kinases/metabolism
  • Proto-Oncogene Proteins/metabolism
  • Proto-Oncogene Proteins c-akt
  • Signal Transduction/drug effects
  • Signal Transduction/physiology
  • Zebrafish/embryology*
  • Zebrafish/genetics
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed: 16174743 Full text @ Proc. Natl. Acad. Sci. USA
Angiopoietin-like protein (Angptl) 1 and Angptl2, which are considered orphan ligands, are highly homologous, particularly in the fibrinogen-like domain containing the putative receptor binding site. This similarity suggests potentially cooperative functions between the two proteins. In this report, the function of Angptl1 and Angptl2 is analyzed by using morpholino antisense technology in zebrafish. Knockdown of both Angptl1 and Angptl2 produced severe vascular defects due to increased apoptosis of endothelial cells at the sprouting stage. In vitro studies showed that Angptl1 and Angptl2 have antiapoptotic activities through the phosphatidylinositol 3-kinase/Akt pathway, and coinjection of constitutively active Akt/protein kinase B mRNA rescued impaired vascular development seen in double knockdown embryos. These results provide a physiological demonstration of the cooperative interaction of Angptl1 and Angptl2 in endothelial cells through phosphatidylinositol 3-kinase/Akt mediated antiapoptotic activities.