Site-Specific Phosphorylation of VEGFR2 Is Mediated by Receptor Trafficking: Insights from a Computational Model
Fig 7
Neuropilin-1 and phosphatases modulate site-specific VEGFR2 phosphorylation.
A-C. Distribution of VEGF-bound VEGFR2 (sum of V·R2, V·N1·R2, and M·V·R2) in HUVECs. Solid lines: Baseline case with NRP1 present; dotted lines: no NRP1 present. Soluble VEGF (Vs), blue lines; bound VEGF (Vb), green lines. For all lines, [V] = 20 ng/mL, HUVEC receptor numbers. D-G. Total VEGFR2 phosphorylated on at least one of Y951, Y1175, and Y1214 (pR2, D), pY1175 (E), pY1214 (F), and total VEGFR2 (G) with NRP1 (solid lines) and without NRP1 (dotted lines). H-I. Model predictions for site-specific VEGFR2 phosphorylation under perturbation of phosphatase activity. H. Model predictions for the experiment in Fig 4F (siRNA to VEPTP), with the addition of a constitutively active TCPTP (as described in Fig 4G). I. Model predictions for exposure of HUVECs to a cell-surface phosphatase that dephosphorylates Y951, Y1175, and Y1214, similar to DEP-1. The impact of increasing phosphatase expression by a factor of 2, 5, or 10 is shown.