Figure 2. Schematic illustration of a suggested mechanism by which Notch signaling inhibits endothelial cell proliferation. Activation of Notch signaling suppresses MAPK and PI3K/Akt pathways. The Notch/MAML-HES cascade likely regulates MAPK and PI3K/Akt pathways indirectly through the induction/suppression of other targeting gene(s) (e.g., suppressing VEGF-R2). This induction or suppression, in turn, mediates Notch’s effect. The signaling cascades from both MAPK and PI3K/Akt pathways ultimately control components of cell cycle machinery, such as Rb and p21^Cip1.