Signaling Required for Blood Vessel Maintenance: Molecular Basis and Pathological Manifestations

Figure 1

Signaling pathways controlling vascular maintenance. While VEGF signaling disrupts VE-cadherin-based junctions through Src-mediated VE-cadherin phosphorylation and internalization, FGF signaling promotes p120 association with VE-cadherin, thus increasing VE-cadherin stability at adherens junctions. Angpt-1 binding to Tie2 at cell-cell contacts leads to formation of Tie2 transdimers which activates Akt and promotes cell survival. S1P binding to S1P1 (Edg1) is able to stabilize endothelial junctions via Rac1 and promotes N-cadherin forward trafficking required for endothelial-pericyte interaction. HEG1-CCM signaling at endothelial junctions enhances junctional stability through Krit1 interaction with β-catenin in the VE-cadherin complex. PDGF-BB secreted from endothelial cells recruit pericytes expressing PDGFRβ. TGF-β produced in endothelial cells induces mural cell differentiation. TGFβRII is also expressed in endothelial cells and controls various endothelial functions.