PUBLICATION

Lysine methylation promotes VEGFR-2 activation and angiogenesis

Authors
Hartsough, E.J., Meyer, R.D., Chitalia, V., Jiang, Y., Marquez, V.E., Zhdanova, I.V., Weinberg, J., Costello, C.E., and Rahimi, N.
ID
ZDB-PUB-140123-28
Date
2013
Source
Science signaling   6(304): ra104 (Journal)
Registered Authors
Zhdanova, Irina
Keywords
none
MeSH Terms
  • Animals
  • Cell Line, Tumor
  • HEK293 Cells
  • Heterografts
  • Humans
  • Lysine/genetics
  • Lysine/metabolism*
  • Methylation
  • Mice
  • Neoplasm Proteins/genetics
  • Neoplasm Proteins/metabolism*
  • Neoplasm Transplantation
  • Neoplasms/genetics
  • Neoplasms/metabolism*
  • Neoplasms/pathology
  • Neovascularization, Pathologic/genetics
  • Neovascularization, Pathologic/metabolism*
  • Neovascularization, Pathologic/pathology
  • Protein Processing, Post-Translational*
  • Vascular Endothelial Growth Factor Receptor-2
  • Zebrafish/genetics
  • Zebrafish/metabolism*
  • Zebrafish Proteins/genetics
  • Zebrafish Proteins/metabolism*
PubMed
24300896 Full text @ Sci. Signal.
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 Lys1041, 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 Lys1041 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 Lys1041 was required for VEGFR-2–mediated angiogenesis in zebrafish and tumor growth in mice. We propose that methylation of Lys1041 promotes the activation of VEGFR-2 and that similar posttranslational modification could also regulate the activity of other receptor tyrosine kinases.

Genes / Markers
Figures
Expression
Phenotype
Mutations / Transgenics
Human Disease / Model
Sequence Targeting Reagents
Fish
Antibodies
Orthology
Engineered Foreign Genes
Mapping