TY - JOUR
T1 - Direct measurements of VEGF–VEGFR2 binding affinities reveal the coupling between ligand binding and receptor dimerization
AU - King, Christopher
AU - Hristova, Kalina
N1 - Funding Information:
This work was supported by National Institutes of Health Grant GM068619, National Science Foundation Grant MCB 1712740, and National Science FoundationGraduateResearchFellowshipDGE-1232825.Theauthorsdeclare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health This article was selected as one of our Editors’ Picks.
Funding Information:
This work was supported by National Institutes of Health Grant GM068619, National Science Foundation Grant MCB 1712740, and National Science Foundation Graduate Research Fellowship DGE-1232825. The authors declare that they have no conflicts of interest with the contents of this article. The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health
Publisher Copyright:
© 2019 King and Hristova.
PY - 2019/6/7
Y1 - 2019/6/7
N2 - 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.
AB - 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.
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U2 - 10.1074/jbc.RA119.007737
DO - 10.1074/jbc.RA119.007737
M3 - Article
C2 - 31023826
AN - SCOPUS:85066942371
SN - 0021-9258
VL - 294
SP - 9064
EP - 9075
JO - Journal of Biological Chemistry
JF - Journal of Biological Chemistry
IS - 23
ER -