ArticleEMBO reports2021
F-domain valency determines outcome of signaling through the angiopoietin pathway.
Article in EMBO reports, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 22 citations in OpenAlex.
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- The promoting effect of modified Dioscorea pills on vascular remodeling in chronic cerebral hypoperfusion via the Ang/Tie signaling pathway.Translational neuroscience · 2023Article
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- Engineering Self-Assembling Protein Nanoparticles for Therapeutic Delivery.Bioconjugate chemistry · 2022Review
- Sci-Seq of Human Fetal Salivary Tissue Introduces Human Transcriptional Paradigms and a Novel Cell Population.Frontiers in dental medicine · 2022Article
- F-domain valency determines outcome of signaling through the angiopoietin pathway.EMBO reports · 2021Article
- Structural insights into the clustering and activation of Tie2 receptor mediated by Tie2 agonistic antibody.Nature communications · 2021Article
- Designed proteins assemble antibodies into modular nanocages.Science (New York, N.Y.) · 2021Article
- Designed proteins assemble antibodies into modular nanocages.bioRxiv : the preprint server for biology · 2020Article
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Authors and funding
14 authors at 1 institution in 1 country.
Funding
Abstract
Angiopoietins 1 and 2 (Ang1 and Ang2) regulate angiogenesis through their similar F-domains by activating Tie2 receptors on endothelial cells. Despite the similarity in the underlying receptor-binding interaction, the two angiopoietins have opposite effects: Ang1 induces phosphorylation of AKT, strengthens cell-cell junctions, and enhances endothelial cell survival while Ang2 can antagonize these effects, depending on cellular context. To investigate the molecular basis for the opposing effects, we examined the phenotypes of a series of computationally designed protein scaffolds presenting the Ang1 F-domain in a wide range of valencies and geometries. We find two broad phenotypic classes distinguished by the number of presented F-domains: Scaffolds presenting 3 or 4 F-domains have Ang2-like activity, upregulating pFAK and pERK but not pAKT, while scaffolds presenting 6, 8, 12, 30, or 60 F-domains have Ang1-like activity, upregulating pAKT and inducing migration and vascular stability. The scaffolds with 6 or more F-domains display super-agonist activity, producing stronger phenotypes at lower concentrations than Ang1. Tie2 super-agonist nanoparticles reduced blood extravasation and improved blood-brain barrier integrity four days after a controlled cortical impact injury.
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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.