Abstract
Vascular endothelial growth factor receptor 2 (VEGFR2) controls angiogenesis and is critically important for normal human development and cancer progression. A recent finding that VEGFR2 can dimerize in the absence of ligand raises the question whether VEGF binds to either VEGFR2 monomers or dimers or to both. Although VEGF-VEGFR2 effective binding constants have been measured, these prior measurements have not discriminated between the association state of the receptor. Because ligand binding is coupled to receptor dimerization, this coupling lends complexity to a seemingly straightforward problem. Here, we unravel this complexity by applying a rigorous thermodynamics approach and performing binding measurements over a broad range of receptor and ligand concentrations. By applying a global fitting procedure to a large data set, we reveal a 45-fold difference between VEGF binding affinities for monomeric and dimeric forms of VEGFR2.