Figure 2
From: Dll4-Notch signaling as a therapeutic target in tumor angiogenesis
Interaction of the Delta-Notch axis with other signaling pathways in endothelial cells. Solid lines denote protein-protein interactions, while dashed lines indicate transcriptional regulation. Binding of VEGF to VEGF receptors (VEGFR2) results in the transcriptional up-regulation of Dll4. Dll4-mediated activation of the Notch receptor on an adjacent endothelial cell leads to the transcriptional repression of VEGFR expression. EphrinB2 is a Dll4-Notch target gene, but also acts upstream of Dll4-Notch signaling as a regulator of VEGFR endocytosis and signaling. Other putative signaling pathways downstream of Dll4-Notch include apelin, ESM-1, Ang2 and Wnt, while FGF, Wnt and Ang1 are potential upstream activators of Dll4 expression.