Effect of exogenous NP-1 on EC development.

(A) When NP-1 was expressed on ECs, signaling by VEGF₁₆₅was enhanced through dimerization of NP-1 and VEGFR-2 (ii) compared with situations in which VEGFR-2 alone was expressed on ECs (i). This may have been caused by conformational changes produced by VEGFR-2 on ECs. (B) A monomer of soluble NP-1 inhibited binding of VEGF₁₆₅ to VEGFR-2 and prevented phosphorylation of VEGFR-2 (i); however, a dimer of soluble NP-1 bound to VEGF and enhanced phosphorylation of VEGFR-2 exogenously (ii). Candidate cells that express NP-1 and affect activation of VEGFR-2 on EC exogenously are neuronal cells, stromal cells in the bone marrow, tumor cells, and so on (iii). However, it is not clear whether the NP-1 on such cell types forms a dimer.