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Lysine methylation promotes VEGFR-2 activation and angiogenesis.
- Source :
-
Science signaling [Sci Signal] 2013 Dec 03; Vol. 6 (304), pp. ra104. Date of Electronic Publication: 2013 Dec 03. - Publication Year :
- 2013
-
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 that methylation of Lys(1041) promotes the activation of VEGFR-2 and that similar posttranslational modification could also regulate the activity of other receptor tyrosine kinases.
- Subjects :
- Animals
Cell Line, Tumor
HEK293 Cells
Heterografts
Humans
Lysine genetics
Methylation
Mice
Neoplasm Proteins genetics
Neoplasm Transplantation
Neoplasms genetics
Neoplasms pathology
Neovascularization, Pathologic genetics
Neovascularization, Pathologic pathology
Vascular Endothelial Growth Factor Receptor-2
Zebrafish genetics
Zebrafish Proteins genetics
Lysine metabolism
Neoplasm Proteins metabolism
Neoplasms metabolism
Neovascularization, Pathologic metabolism
Protein Processing, Post-Translational
Zebrafish metabolism
Zebrafish Proteins metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1937-9145
- Volume :
- 6
- Issue :
- 304
- Database :
- MEDLINE
- Journal :
- Science signaling
- Publication Type :
- Academic Journal
- Accession number :
- 24300896
- Full Text :
- https://doi.org/10.1126/scisignal.2004289