ArticleMolecular and cellular biology2011
PEST motif serine and tyrosine phosphorylation controls vascular endothelial growth factor receptor 2 stability and downregulation.
Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 58 papers.
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Who cites it
58 citing papers in PubMed, 102 citations in OpenAlex.
- ABL kinases regulate FGF signaling independent of CRK phosphorylation to prevent Peters anomaly type II.Nature communications · 2026Article
- Biology of PEST-containing nuclear proteins as potential targets in ovarian cancer (Review).Oncology letters · 2026Review
- Vascular endothelial growth factor signaling in health and disease: from molecular mechanisms to therapeutic perspectives.Signal transduction and targeted therapy · 2025Review
- New insights into the role of ubiquitination in angiogenesis (Review).International journal of molecular medicine · 2025Review
- Regulation of PEST-containing nuclear proteins in cancer cells: implications for cancer biology and therapy.Frontiers in oncology · 2025Review
- Protein pyrophosphorylation by inositol phosphates: a novel post-translational modification in plants?Frontiers in plant science · 2024Review
- Calreticulin Regulates SARS-CoV-2 Spike Protein Turnover and Modulates SARS-CoV-2 Infectivity.Cells · 2023Article
- Bladder cancer: therapeutic challenges and role of 3D cell culture systems in the screening of novel cancer therapeutics.Cancer cell international · 2023Review
- Mitochondria in endothelial cells angiogenesis and function: current understanding and future perspectives.Journal of translational medicine · 2023Review
- Protein post-translational modifications in the regulation of cancer hallmarks.Cancer gene therapy · 2023Review
- Exploiting E3 ubiquitin ligases to reeducate the tumor microenvironment for cancer therapy.Experimental hematology & oncology · 2023Review
- Structure-Guided Prediction of the Functional Impact of DCLK1 Mutations on Tumorigenesis.Biomedicines · 2023Review
- PRMT4-mediated arginine methylation promotes tyrosine phosphorylation of VEGFR-2 and regulates filopodia protrusions.iScience · 2022Article
- Comprehensive Analysis of VEGFR2 Expression in HPV-Positive and -Negative OPSCC Reveals Differing VEGFR2 Expression Patterns.Cancers · 2021Article
- The cell adhesion molecule TMIGD1 binds to moesin and regulates tubulin acetylation and cell migration.Journal of biomedical science · 2021Article
- The P-type ATPase transporter ATP7A promotes angiogenesis by limiting autophagic degradation of VEGFR2.Nature communications · 2021Article
- NEDD4 regulates ubiquitination and stability of the cell adhesion molecule IGPR-1 via lysosomal pathway.Journal of biomedical science · 2021Article
- An engineered channelrhodopsin optimized for axon terminal activation and circuit mapping.Communications biology · 2021Article
- Generation of the short TRIM32 isoform is regulated by Lys 247 acetylation and a PEST sequence.PloS one · 2021Article
- Raftlin is recruited by neuropilin-1 to the activated VEGFR2 complex to control proangiogenic signaling.Angiogenesis · 2020Article
Corrections and comments
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
The internalization and degradation of vascular endothelial growth factor receptor 2 (VEGFR-2), a potent angiogenic receptor tyrosine kinase, is a central mechanism for the regulation of the coordinated action of VEGF in angiogenesis. Here, we show that VEGFR-2 is ubiquitinated in response to VEGF, and Lys 48-linked polyubiquitination controls its degradation via the 26S proteosome. The degradation and ubiquitination of VEGFR-2 is controlled by its PEST domain, and the phosphorylation of Ser1188/Ser1191 is required for the ubiquitination of VEGFR-2. F-box-containing β-Trcp1 ubiquitin E3 ligase is recruited to S1188/S1191 VEGFR-2 and mediates the ubiquitination and degradation of VEGFR-2. The PEST domain also controls the activation of p38 mitogen-activated protein kinase (MAPK) through phospho-Y1173. The activation of p38 stabilizes VEGFR-2, and its inactivation accelerates VEGFR-2 downregulation. The VEGFR-2-mediated activation of p38 is established through the protein kinase A (PKA)/MKK6 pathway. PKA is recruited to VEGFR-2 through AKAP1/AKAP149, and its phosphorylation requires Y1173 of VEGFR-2. The study has identified a unique mechanism in which VEGFR-2 stability and degradation is modulated. The PEST domain acts as a dual modulator of VEGFR-2; the phosphorylation of S1188/S1191 controls ubiquitination and degradation via β-Trcp1, where the phosphorylation of Y1173 through PKA/p38 MAPK controls the stability of VEGFR-2.
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Registered trials
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.