Fig. 6.

Model of BMP6-induced vascular permeability. At endothelial cell AJs, BMP6 induces receptor complex assembly, activates c-Src via phosphorylation at Tyr416 and promotes c-Src-dependent phosphorylation of VE-cadherin at Tyr685 (red arrows). In addition, BMP signaling induces VE-cadherin internalization (purple arrows). Collectively, these mechanisms trigger AJ remodeling and ultimately result in hyperpermeability (red and purple box). Moreover, VE-cadherin functions as a positive regulator of vascular BMP signal transduction. Clustered VE-cadherin is needed for efficient signaling and stabilizes the ALK2–BMPRII receptor complex (blue arrow), thus facilitating SMAD1/5-dependent signaling (blue box).