Characterizing the effects of the juxtamembrane domain on vascular endothelial growth factor receptor-2 enzymatic activity, autophosphorylation, and inhibition by axitinib

Combination of kinetic, biophysical, and structural methods were applied to perform highly purified preparation and characterize the receptor tyrosine kinase VEGFR2 catalytic domain without (VEGFR2-CD) and with (VEGFR2-CD/JM) the juxtamembrane (JM) domain. The results obtained provide insight into the thermodynamic origin of the potency differences of VEGFR2 JM domain and identified potential functions of the VEGFR2 JM domain with implications to both receptor biology and inhibitor design.