ArticleMolecular biology of the cell2005
The carboxyl terminus of VEGFR-2 is required for PKC-mediated down-regulation.
Article in Molecular biology of the cell, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 82 citations in OpenAlex.
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- Calreticulin Regulates SARS-CoV-2 Spike Protein Turnover and Modulates SARS-CoV-2 Infectivity.Cells · 2023Article
- Protein post-translational modifications in the regulation of cancer hallmarks.Cancer gene therapy · 2023Review
- βNature communications · 2022Article
- Protein kinase D up-regulates transcription ofThe Journal of biological chemistry · 2019Article
- Opioids: Modulators of angiogenesis in wound healing and cancer.Oncotarget · 2017Review
- Article
- Activation of Vascular Endothelial Growth Factor (VEGF) Receptor 2 Mediates Endothelial Permeability Caused by Cyclic Stretch.The Journal of biological chemistry · 2016Article
- Hypoxia-induced expression of phosducin-like 3 regulates expression of VEGFR-2 and promotes angiogenesis.Angiogenesis · 2015Article
- The cellular response to vascular endothelial growth factors requires co-ordinated signal transduction, trafficking and proteolysis.Bioscience reports · 2015Review
- Synergistic Binding of Vascular Endothelial Growth Factor-A and Its Receptors to Heparin Selectively Modulates Complex Affinity.The Journal of biological chemistry · 2015Article
- Emerging roles of post-translational modifications in signal transduction and angiogenesis.Proteomics · 2015Review
- Lysine methylation promotes VEGFR-2 activation and angiogenesis.Science signaling · 2013Article
- Identification of PDCL3 as a novel chaperone protein involved in the generation of functional VEGF receptor 2.The Journal of biological chemistry · 2013Article
- S100A1 deficiency impairs postischemic angiogenesis via compromised proangiogenic endothelial cell function and nitric oxide synthase regulation.Circulation research · 2013Article
- SCF(β-TRCP) suppresses angiogenesis and thyroid cancer cell migration by promoting ubiquitination and destruction of VEGF receptor 2.The Journal of experimental medicine · 2012Article
- Signal transduction by vascular endothelial growth factor receptors.Cold Spring Harbor perspectives in medicine · 2012Review
- The ubiquitin-proteasome system meets angiogenesis.Molecular cancer therapeutics · 2012Review
- Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Vascular endothelial growth factor receptor-2 (VEGFR-2/Flk-1) is a receptor tyrosine kinase (RTK) whose activation regulates angiogenesis. The regulatory mechanisms that attenuate VEGFR-2 signal relay are largely unknown. Our study shows that VEGFR-2 promotes phosphorylation of c-Cbl, but activation, ubiquitylation, and down-regulation of VEGFR-2 are not influenced by c-Cbl activity. A structure-function analysis of VEGFR-2 and pharmacological approach revealed that down-regulation of VEGFR-2 is mediated by a distinct mechanism involving PKC. A tyrosine mutant VEGFR-2, defective in PLC-gamma1 activation underwent down-regulation efficiently in response to ligand stimulation, suggesting that activation of classical PKCs are not involved in VEGFR-2 down-regulation. Further studies showed that the ectodomain of VEGFR-2 is dispensable for PKC-dependent down-regulation. Progressive deletion of the carboxyl-terminal domain showed that at least 39 amino acids within the carboxyl-terminal domain, immediately C-terminal to the kinase domain, is required for efficient PKC-mediated down-regulation of VEGFR-2. Mutation of serine sites at 1188 and 1191, within this 39 amino acid region, compromised the ability of VEGFR-2 to undergo efficient ligand-dependent down-regulation. Altogether the results show that the regulatory mechanisms involved in the attenuation of VEGFR-2 activation is mediated by nonclassical PKCs and the presence of serine sites in the carboxyl terminal of VEGFR-2.
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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.