Site-Specific Phosphorylation of VEGFR2 Is Mediated by Receptor Trafficking: Insights from a Computational Model
Fig 9
Differences in molecular interactions of VEGF isoforms are predicted to account for changes in observed vascular phenotype.
A. VEGF121 does not bind NPR1 or extracellular matrix proteins (M), leading to slow VEGFR2 ligation (due to lack of NRP1-mediated VEGF-VEGFR2 binding), fast internalization (no immobilization of VEGF121), and a lack of recycling via the Rab11 pathway. B. VEGF165 binds both NRP1 and extracellular matrix species, leading to faster VEGFR2 ligation, but slower internalization of VEGFR2 compared to stimulation with VEGF121. The Rab11 recycling pathway is accessible to VEGF165-NRP1-VEGFR2 complexes. C. VEGF189 binds to extracellular matrix species and NRP1 more strongly than VEGF165. This results in moderate VEGFR2 ligation speed (NRP1 must compete with matrix species (M) for VEGF) and slow VEGFR2 internalization.