Dataset Information

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 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.

SUBMITTER: Hartsough EJ

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

REPOSITORIES: biostudies-literature

ACCESS DATA

Publications

Lysine methylation promotes VEGFR-2 activation and angiogenesis.

Hartsough Edward J EJ Meyer Rosana D RD Chitalia Vipul V Jiang Yan Y Marquez Victor E VE Zhdanova Irina V IV Weinberg Janice J Costello Catherine E CE Rahimi Nader N

Science signaling 20131203 304

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 ...[more]

PMID: 24300896

Similar Datasets

Project description:Long noncoding RNAs (lncRNAs) can compete with endogenous RNAs to modulate the gene expression and contribute to oncogenesis and tumor metastasis. lncRNA NKX2-1-AS1 (NKX2-1 antisense RNA 1) plays a pivotal role in cancer progression and metastasis; however, the contribution of aberrant expression of NKX2-1-AS1 and the mechanism by which it functions as a competing endogenous RNA (ceRNA) in gastric cancer (GC) remains elusive. NKX2-1-AS1 expression was detected in paired tumor and nontumor tissues of 178 GC patients by quantitative reverse transcription PCR (qRT-PCR). Using loss-of-function and gain-of-function experiments, the biological functions of NKX2-1-AS1 were evaluated both in vitro and in vivo. Further, to assess that NKX2-1-AS1 regulates angiogenic processes, tube formation and co-culture assays were performed. RNA binding protein immunoprecipitation (RIP) assay, a dual-luciferase reporter assay, quantitative PCR, Western blot, and fluorescence in situ hybridization (FISH) assays were performed to determine the potential molecular mechanism underlying this ceRNA. The results indicated that NKX2-1-AS1 expression was upregulated in GC cell lines and tumor tissues. Overexpression of NKX2-1-AS1 was significantly associated with tumor progression and enhanced angiogenesis. Functionally, NKX2-1-AS1 overexpression promoted GC cell proliferation, metastasis, invasion, and angiogenesis, while NKX2-1-AS1 knockdown restored these effects, both in vitro and in vivo. RIP and dual-luciferase assays revealed that the microRNA miR-145-5p is a direct target of NKX2-1-AS1 and that NKX2-1-AS1 serves as a ceRNA to sponge miRNA and regulate angiogenesis in GC. Moreover, serpin family E member 1 (SERPINE1) is an explicit target for miR-145-5p; besides, the NKX2-1-AS1/miR-145-5p axis induces the translation of SERPINE1, thus activating the VEGFR-2 signaling pathway to promote tumor progression and angiogenesis. NKX2-1-AS1 overexpression is associated with enhanced tumor cell proliferation, angiogenesis, and poor prognosis in GC. Collectively, NKX2-1-AS1 functions as a ceRNA to miR-145-5p and promotes tumor progression and angiogenesis by activating the VEGFR-2 signaling pathway via SERPINE1.

Dataset Information

Lysine methylation promotes VEGFR-2 activation and angiogenesis.

Publications

Lysine methylation promotes VEGFR-2 activation and angiogenesis.

Similar Datasets

OmicsDI is part of the ELIXIR infrastructure

Tweets