Site-Specific Phosphorylation of VEGFR2 Is Mediated by Receptor Trafficking: Insights from a Computational Model
Fig 1
A. Biochemical Reactions. Interactions between VEGF, VEGFR2, NRP1, and an extracellular matrix proteoglycan (M) are summarized. VEGF can bind VEGFR2, NRP1, and M. NRP1 and M cannot be present in the same complex (as they bind to the same surface of VEGF), and VEGFR2 and NRP1 cannot form a complex without VEGF. B. Trafficking Pathways. Surface molecular complexes can be internalized with rate constant kintn. Rab4/5-resident molecular complexes can be degraded (rate constant kdegr), recycled (rate constant krec4), or transferred to the Rab11 compartment (rate constant k4to11). Rab11 endosome-resident complexes are recycled with rate constant krec11. New surface receptors are produced at rate s. C. Phosphorylation Reactions. Intracellular tyrosine residues Y951, Y1175, and Y1214 are phosphorylated and dephosphorylated independently. D. Overview of signaling pathways and cellular behaviors downstream of tyrosine residues Y951, Y1175, and Y1214 on VEGFR2.