A computational analysis of in vivo VEGFR activation by multiple co-expressed ligands
(A) Total soluble growth factor (in available interstitial fluid) and immobilized growth factor (in innermost 25nm of EBM) accessible to ECs. Growth factor bound to EC receptors is not included in this plot. (B) Break-down of EC surface-bound ligand, by isoform. Note the difference in quantities of total ligated VEGFR2, VEGFR1, and NRP1 (panel C). (C) Occupancy of VEGFR2, VEGFR1, and NRP1 on ECs, broken down by ligand and NRP1-binding. VEGFR2 occupancy is shown on the cell surface, in early signaling endosomes (Rab4/5), and in recycling endosomes (Rab11), while VEGFR1 and NRP1 are shown only on the cell surface. Quantities are given in pM of total tissue in the “Main Body Mass” compartment. (D) VEGFR2, VEGFR1, and NRP1 ligation on ECs, excluding receptor not bound to ligand. Complexes not listed in the legend are present at levels too low to be seen in the figure. (E) Break-down of percentage of EC surface VEGFR1 and VEGFR2 ligation comprised by each isoform, compared to the relative production of each isoform. Production fractions are calculated separately for VEGF and PlGF, while for receptor binding the combined distribution is shown.