Ligand-Receptor interactions for the VEGF and Semaphorin families.

<p>VEGF ligands bind to and signal through three RTKs: VEGFR1, VEGFR2, and VEGFR3 (blue). Neuropilins are in red, with numbers to distinguish between neuropilin-1 and neuropilin-2. Semaphorin ligands bind to and signal through Plexins A-D (green). Many (but not all) members of the VEGF and Sema3 families use Neuropilin 1 or 2 as a co-receptor for binding to the canonical signaling receptors. This competition for Neuropilin is thought to represent one mechanism by which VEGF and Semaphorin ligands antagonize each other; in addition, the downstream signaling of VEGFRs and Plexins can have opposite function. Note that not all splice isoforms of VEGF-A, VEGF-B, and PlGF can bind to the receptors indicated, and that kinetic rates of binding vary among isoforms.