Role of VEGF-C signaling in vasculogenesis and angiogenesis.

(A) In this model, VEGF-C transduced different signals through VEGFR-2 and VEGFR-3 in vasculoangiogenesis. VEGF-C signaling through VEGFR-2 (red arrow) enhances VEGF-A signaling, promoting vasculoangiogenesis. VEGFR-3 works as a trapper of VEGF-C for the inhibition of VEGF-C signaling through VEGFR-2 (green arrow). The extracellular domain of VEGFRs is depicted at the top, and the split kinase domains are shown at the C-terminal to the transmembrane region. Various ligand and receptor combinations are depicted by arrows. Ig indicates immunoglobulin-like domain; Kinase, tyrosine kinase domain; TM, transmembrane domain. (B) Signal disturbance in VEGFR-3–deficient embryos. In VEGFR-3–deficient embryos, vascular endothelial cells show proliferation but, on the other hand, hematopoiesis is suppressed by the disturbance of signaling of VEGF-C.