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Angiopoietin-2 Secretion by Endothelial Cell Exosomes

Authors :
Themis R. Kyriakides
Michael Simons
Zhen W. Zhuang
Jiasheng Zhang
William C. Sessa
Rong Ju
Anthony A. Lanahan
Source :
Journal of Biological Chemistry. 289:510-519
Publication Year :
2014
Publisher :
Elsevier BV, 2014.

Abstract

Angiopoietin-2 (Ang2) is an extracellular protein and one of the principal ligands of Tie2 receptor that is involved in the regulation of vascular integrity, quiescence, and inflammation. The mode of secretion of Ang2 has never been established, however. Here, we provide evidence that Ang2 is secreted from endothelial cells via exosomes and that this process is inhibited by the PI3K/Akt/endothelial nitric oxide synthase (eNOS) signaling pathway, whereas it is positively regulated by the syndecan-4/syntenin pathway. Vascular defects in Akt1 null mice arise, in part, because of excessive Ang2 secretion and can be rescued by the syndecan-4 knock-out that reduces extracellular Ang2 levels. This novel mechanism connects three critical signaling pathways: angiopoietin/Tie2, PI3K/Akt/eNOS, and syndecan/syntenin, which play important roles in vascular growth and stabilization.

Details

ISSN :
00219258
Volume :
289
Database :
OpenAIRE
Journal :
Journal of Biological Chemistry
Accession number :
edsair.doi...........8e58827e8ff4e6025a84b9b20868dc2f
Full Text :
https://doi.org/10.1074/jbc.m113.506899