Reactive Oxygen Species in Vascular Formation and Development
Figure 1
Regulation of intercellular VE-cadherin disruption between endothelial cells by reactive oxygen species and VEGF signaling during EC migration. In basal state, clustering of VE-cadherins between endothelial cells mediate intercellular adhesions. VE-cadherin forms a dimer and bind directly to p120 and -catenin, with the latter associated with α-catenin to bridge the actin cytoskeleton. Upon VEGF stimulation, TSAd-dependent Src activation recruits IQGAP1, a multifunctional scaffold protein, to assist association of Rac1 with other Nox subunits (a). Subsequent ROS production by NOx phosphorylate VE-cadherin and -catenins, leading to disassembly of VE-cadherin-catenin complex and EC junctional breakdown, which in turn results in EC migration (b). On the other hand, -catenin phosphorylation by VEGF-induced FAK activation and p120 phosphorylation by thrombin-activated PKC-α also promotes the breakdown of endothelial cell tight junctions. Moreover, phosphorylation of VE-cadherin in the cytoplasmic tail via VEGF-VEFGR-Src-Vav2-Rac-PAK axis promotes β-arrestin2 dependent of its internalization and disassembly (c).
