Roles of reactive oxygen species in angiopoietin-1/tie-2 receptor signaling

SPECIFIC AIMSRecent studies have indicated that reactive oxygen species (ROS) play important roles as second messengers in regulating signaling of receptor tyrosine kinases (RTKs) such as those of vascular endothelial growth factor (VEGF) in endothelial cells (ECs). These roles are mediated through selective regulation of protein phosphorylation of the mitogen-activated protein kinases (MAPKs), the phosphatidylinositol 3′-kinase (PI-3 kinase), protein kinase B (AKT), and other signaling pathways. It has also been reported that the NADPH oxidase enzyme complex is an important molecular source of ROS generated in response to activated receptors. Tie-2 receptors are RTKs selectively expressed in ECs and play an important role in embryonic vascular development and promote differentiation, tube formation, sprouting, migration, adherence, and survival of ECs. Angiopoietin-1 (Ang-1) has recently been identified as the main endogenous agonist for tie-2 receptors and exposure to Ang-1 triggers autophosphorylation ...