Schematic outline of the contribution of ligand binding to HS and NRP1 in endothelial cell responses. (A) Outline of symbols used in panel B. (B) Depiction of VEGF/VEGF receptor complexes induced by VEGF-A165, VEGF-A121, and VEGF-E-NZ2. Note that we do not exclude that HS as well as NRP1 may bind directly to VEGFR-2, but for simplicity, this is not shown. P in yellow symbols in VEGFR-2 indicates major phosphorylation sites.2 Below is shown a summary of the data in this study in terms of signal transduction (activation of Erk1/2, Akt, and p38MAPK) and biologic readout (sprouting, branching).