Figure 1.

Signaling pathways that contribute to VEGF induced angiogenesis, and a proposal for their participation in the development of the utero-placental interface by participating in proliferative, invasive, vasodilatory and permeability changes essential for cell invasion and angiogenesis. VEGF activates eNOS through pathways including Akt/PKB, Ca⁺²/CaM, and PKC [20-24]. Flt-1 may negatively regulate KDR, but might also promote its activity [20]. Bradykinin stimulates eNOS through Ca⁺², induces EC to form tubes, and transactivates the KDR [26]. The factors studied have been depicted in orange areas surrounded by a red border, known mechanisms of downstream activation by interrupted arrows, and unknown mechanism of downstream activation by interrupted arrow. VEGF, vascular endothelial growth factor; BK, bradykinin; eNOS, endothelial nitric oxide synthase; PLC β, phospholipase C -β; PLCγ, phospholipase C -γ; DAG, diacylglycerol; IP3, inositol (1,4,5)-triphosphate; PKC, protein kinase C; MAPK, mitogen-activated protein kinase; FAK, focal adhesion kinase; PI3K, phosphoinositide 3-kinase; p38 MAPK, p38 mitogen-activated protein; Erk, extracellular regulated kinase; HSP27, heat protein; CaM, calmodulin; EC, endothelial cell.