Lysine methylation promotes VEGFR-2 activation and angiogenesis.

ABSTRACT: Activation of vascular endothelial growth factor receptor-2 (VEGFR-2), an endothelial cell receptor tyrosine kinase, promotes tumor angiogenesis and ocular neovascularization. We report the methylation of VEGFR-2 at multiple Lys and Arg residues, including Lys(1041), a residue that is proximal to the activation loop of the kinase domain. Methylation of VEGFR-2 was independent of ligand binding and was not regulated by ligand stimulation. Methylation of Lys(1041) enhanced tyrosine phosphorylation and kinase activity in response to ligands. Additionally, interfering with the methylation of VEGFR-2 by pharmacological inhibition or by site-directed mutagenesis revealed that methylation of Lys(1041) was required for VEGFR-2-mediated angiogenesis in zebrafish and tumor growth in mice. We propose

SUBMITTER: Hartsough EJ 

PROVIDER: S-EPMC4108444 | biostudies-literature | 2013 Dec

REPOSITORIES: biostudies-literature