Characterization and kinetic mechanism of catalytic domain of human vascular endothelial growth factor receptor-2 tyrosine kinase (VEGFR2 TK), a key enzyme in angiogenesis.
作者： Camran V. Parast , Barbara Mroczkowski , Chris Pinko , Shawn Misialek , Godrej Khambatta
DOI: 10.1021/BI981291F
关键词:
摘要: Vascular endothelial growth factor (VEGF) is a dimeric protein which induces formation of new blood vessels (angiogenesis) through binding to VEGF-receptor-2 tyrosine kinase (VEGFR2 TK) or KDR (kinase insert domain-containing receptor) on the surface cells. Angiogenesis has been shown be essential for malignancy tumors; therefore, VEGFR2 TK potential therapeutic target treatment cancer. Sequence homology studies indicate that contains three domains: extracellular (ligand-binding domain), transmembrane, and intracellular (catalytic domain). In this work, catalytic domain was cloned expressed in soluble active form using baculovirus expression system. absence ligand, enzyme catalyze its autophosphorylation time-dependent enzyme-concentration-dependent manner, consistent with trans mechanism reaction. Mass spectrometry analysis revealed incorporation 5.5 ± 0.5 mol phosphate/mole enz...
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