Neuropilin-2 and neuropilin-1 are receptors for the 165-amino acid form ofvascular endothelial growth factor (VEGF) and of placenta growth factor-2,but only neuropilin-2 functions as a receptor for the 145-amino acid form of VEGF

Neuropilin-1 (np-1) and neuropilin-2 (np-2) are receptors for axon guidance factors belonging to the class 3 semaphorins. np-1 also binds to the 165-a mino acid heparin-binding form of VEGF (VEGF(165)) but not to the shorter V EGF(121) form, which lacks a heparin binding ability. We report that human umbilical vein-derived endothelial cells express the a17 and a22 splice for ms of the np-2 receptor. Both np-2 forms bind VEGF(165) with high affinity in the presence of heparin (K-D 1.3 x 10(-10) M) but not VEGF(121). np-2 al so binds the heparin-binding form of placenta growth factor. These binding characteristics resemble those of np-l. VEGF,, is a secreted heparin bindin g VEGF form that contains the peptide encoded by exon 6 of VEGF but not the peptide encoded VEGF(145) binds to by exon 7, which is present in VEGF(165 ).VEGF(145) binds to np-2 with high affinity (K-D 7 x 10(-10) M). Surprisin gly, VEGF(145) did not bind to np-1. Indeed, VEGF(145) does not bind to MDA -MB-231 breast cancer cells, which predominantly express np-l. By contrast, VEGF(145) binds to human umbilical rein-derived endothelial cells, which e xpress both np-l and np-2. The binding of VEGF(165) to porcine aortic endot helial cells expressing recombinant np-2 did not affect the proliferation o r migration of the cells. Nevertheless, it is possible that VEGF-induced np -2-mediated signaling will take place only in the presence of other VEGF re ceptors such as VEGF receptor-1 or VEGF receptor-2.