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Journal article
Lysine Methylation Promotes VEGFR-2 Activation and Angiogenesis
Science signaling, v 6(304), pp ra104-ra104
03 Dec 2013
PMID: 24300896
Featured in Collection : UN Sustainable Development Goals @ Drexel
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.
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Details
- Title
- Lysine Methylation Promotes VEGFR-2 Activation and Angiogenesis
- Creators
- Edward J. Hartsough - Boston UniversityRosana D. Meyer - Boston UniversityVipul Chitalia - Harvard–MIT Division of Health Sciences and TechnologyYan Jiang - Boston UniversityVictor E. Marquez - Frederick National Laboratory for Cancer ResearchIrina V. Zhdanova - Boston Medical CenterJanice Weinberg - Boston UniversityCatherine E. Costello - Boston UniversityNader Rahimi - Boston University
- Publication Details
- Science signaling, v 6(304), pp ra104-ra104
- Publisher
- Amer Assoc Advancement Science
- Number of pages
- 7
- Grant note
- N01 HHSN268201000031C / NIH/National Heart, Lung, and Blood Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Heart Lung & Blood Institute (NHLBI) DK080946 / K08 award (NIH/National Institute of Diabetes and Digestive and Kidney Diseases) K08DK080946 / NATIONAL INSTITUTE OF DIABETES AND DIGESTIVE AND KIDNEY DISEASES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of Diabetes & Digestive & Kidney Diseases (NIDDK) R01EY017955; P41 RR010888/GM104603; S10 RR020946 / NIH/National Eye Institute; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI) Massachusetts Lions Foundation S10RR020946 / NATIONAL CENTER FOR RESEARCH RESOURCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Center for Research Resources (NCRR) Department of Pathology, Boston University Intramural Research Program of the NIH, National Cancer Institute, Center for Cancer Research; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Cancer Institute (NCI) P41GM104603 / NATIONAL INSTITUTE OF GENERAL MEDICAL SCIENCES; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Institute of General Medical Sciences (NIGMS) K08 award (Department of Medicine Career Investment Award) R01EY017955 / NATIONAL EYE INSTITUTE; United States Department of Health & Human Services; National Institutes of Health (NIH) - USA; NIH National Eye Institute (NEI)
- Resource Type
- Journal article
- Language
- English
- Academic Unit
- Pharmacology and Physiology
- Web of Science ID
- WOS:000327941400002
- Scopus ID
- 2-s2.0-84889238946
- Other Identifier
- 991020531971004721
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- Collaboration types
- Domestic collaboration
- Web of Science research areas
- Biochemistry & Molecular Biology
- Cell Biology