TY - JOUR
T1 - Cooperative interactions between VEGFR2 extracellular Ig-like subdomains ensure VEGFR2 dimerization
AU - King, Christopher
AU - Wirth, Daniel
AU - Workman, Samuel
AU - Hristova, Kalina
N1 - Funding Information:
Supported by NSF MCB 1157687 and NIH GM068619 (to KH), and an NSF Graduate Research Fellowship DGE-1232825 (to CK).
Publisher Copyright:
© 2017 Elsevier B.V.
PY - 2017/11
Y1 - 2017/11
N2 - Background Prior studies have suggested that the interactions occurring between VEGFR2 extracellular domains in the absence of ligand are complex. Here we seek novel insights into these interactions, and into the role of the different Ig-like domains (D1 through D7) in VEGFR2 dimerization. Methods We study the dimerization of a single amino acid mutant and of three deletion mutants in the plasma membrane using two photon microscopy and fully quantified spectral imaging. Results We demonstrate that a set of cooperative interactions between the different Ig-like domains ensure that VEGFR2 dimerizes with a specific affinity instead of forming oligomers. Conclusions The contributions of subunits D7 and D4 seem to be the most critical, as they appear essential for strong lateral interactions and for the formation of dimers, respectively. General significance This study provides new insights into the mechanism of VEGFR2 dimerization and activation.
AB - Background Prior studies have suggested that the interactions occurring between VEGFR2 extracellular domains in the absence of ligand are complex. Here we seek novel insights into these interactions, and into the role of the different Ig-like domains (D1 through D7) in VEGFR2 dimerization. Methods We study the dimerization of a single amino acid mutant and of three deletion mutants in the plasma membrane using two photon microscopy and fully quantified spectral imaging. Results We demonstrate that a set of cooperative interactions between the different Ig-like domains ensure that VEGFR2 dimerizes with a specific affinity instead of forming oligomers. Conclusions The contributions of subunits D7 and D4 seem to be the most critical, as they appear essential for strong lateral interactions and for the formation of dimers, respectively. General significance This study provides new insights into the mechanism of VEGFR2 dimerization and activation.
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U2 - 10.1016/j.bbagen.2017.08.021
DO - 10.1016/j.bbagen.2017.08.021
M3 - Article
C2 - 28847506
AN - SCOPUS:85029394358
SN - 0304-4165
VL - 1861
SP - 2559
EP - 2567
JO - Biochimica et Biophysica Acta - General Subjects
JF - Biochimica et Biophysica Acta - General Subjects
IS - 11
ER -