ArticlePloS one2012
Integrin β3 crosstalk with VEGFR accommodating tyrosine phosphorylation as a regulatory switch.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 74 citations in OpenAlex.
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- Secretome of endothelial progenitor cells from stroke patients promotes endothelial barrier tightness and protects against hypoxia-induced vascular leakage.Stem cell research & therapy · 2021Article
- Semaphorin 3fa Controls Ocular Vascularization From the Embryo Through to the Adult.Investigative ophthalmology & visual science · 2021Article
- Differential effects of risuteganib and bevacizumab on AMD cybrid cells.Experimental eye research · 2021Article
- VEGFR2 survival and mitotic signaling depends on joint activation of associated C3ar1/C5ar1 and IL-6R-gp130.Journal of cell science · 2019Article
- Recombinant RGD-disintegrin DisBa-01 blocks integrin αCell communication and signaling : CCS · 2019Article
- Discoidin-domain receptor coordinates cell-matrix adhesion and collective polarity in migratory cardiopharyngeal progenitors.Nature communications · 2019Article
- Computational modeling of synergistic interaction between αVβ3 integrin and VEGFR2 in endothelial cells: Implications for the mechanism of action of angiogenesis-modulating integrin-binding peptides.Journal of theoretical biology · 2018Article
- Enhanced VEGF signalling mediates cerebral neovascularisation via downregulation of guidance protein ROBO4 in a rat model of diabetes.Diabetologia · 2017Article
- NG2 Proteoglycan Enhances Brain Tumor Progression by Promoting Beta-1 Integrin Activation in both Cis and Trans Orientations.Cancers · 2017Review
- Mechanisms and regulation of endothelial VEGF receptor signalling.Nature reviews. Molecular cell biology · 2016Review
- Article
- EGFRvIII/integrin β3 interaction in hypoxic and vitronectinenriching microenvironment promote GBM progression and metastasis.Oncotarget · 2016Article
- Synthesis, Characterization, and Biological Evaluation of a Dual-Action Ligand Targeting αvβ3 Integrin and VEGF Receptors.ChemistryOpen · 2015Article
- Integrin function in vascular biology: a view from 2013.Current opinion in hematology · 2014Review
- A biomimetic collagen derived peptide exhibits anti-angiogenic activity in triple negative breast cancer.PloS one · 2014Article
- Distinct functions for Rap1 signaling in vascular morphogenesis and dysfunction.Experimental cell research · 2013Review
- Domain 2 of uPAR regulates single-chain urokinase-mediated angiogenesis through β1-integrin and VEGFR2.American journal of physiology. Heart and circulatory physiology · 2013Article
- Regulation of endothelial cell differentiation and specification.Circulation research · 2013Review
Corrections and comments
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Authors and funding
10 authors at 4 institutions in 1 country.
Funding
Abstract
Integrins mediate cell adhesion, migration, and survival by connecting intracellular machinery with the surrounding extracellular matrix. Previous studies demonstrated the importance of the interaction between β(3) integrin and VEGF type 2 receptor (VEGFR2) in VEGF-induced angiogenesis. Here we present in vitro evidence of the direct association between the cytoplasmic tails (CTs) of β(3) and VEGFR2. Specifically, the membrane-proximal motif around (801)YLSI in VEGFR2 mediates its binding to non-phosphorylated β(3)CT, accommodating an α-helical turn in integrin bound conformation. We also show that Y(747) phosphorylation of β(3) enhances the above interaction. To demonstrate the importance of β(3) phosphorylation in endothelial cell functions, we synthesized β(3)CT-mimicking Y(747) phosphorylated and unphosphorylated membrane permeable peptides. We show that a peptide containing phospho-Y(747) but not F(747) significantly inhibits VEGF-induced signaling and angiogenesis. Moreover, phospho-Y(747) peptide exhibits inhibitory effect only in WT but not in β(3) integrin knock-out or β(3) integrin knock-in cells expressing β(3) with two tyrosines substituted for phenylalanines, demonstrating its specificity. Importantly, these peptides have no effect on fibroblast growth factor receptor signaling. Collectively these data provide novel mechanistic insights into phosphorylation dependent cross-talk between integrin and VEGFR2.
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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.