ArticleCell2015
Tuning cytokine receptor signaling by re-orienting dimer geometry with surrogate ligands.
Article in Cell, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 107 papers, 1 of them a synthesis that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
107 citing papers in PubMed, 1 synthesis or guideline pooled it, 169 citations in OpenAlex.
- JAK inhibitors and COVID-19.Journal for immunotherapy of cancer · 2022Pooled it
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- Realizing the potential of agonistic antibody immunotherapy.Nature reviews. Drug discovery · 2026Review
- Mapping and engineering the human cell-cell interactome.Nature biotechnology · 2026Review
- Engineering trispecific IL-2 receptor agonistic antibodies through geometry optimization for enhanced Treg targeting.Nature communications · 2026Article
- Transcriptome, Proteome, and Metabolome Features in Diarrhea Challenge of Preweaning Piglets via Multi-Omics Integration Analyses.Animals : an open access journal from MDPI · 2026Article
- Computational design of synthetic receptors with programmable signalling activity for enhanced cancer T cell therapy.Nature biomedical engineering · 2026Article
- Tuning insulin receptor signaling using de novo-designed agonists.Molecular cell · 2025Article
- Tuning of G-CSFR signaling by de novo-designed agonists.Molecular therapy : the journal of the American Society of Gene Therapy · 2025Article
- Geometric Tuning of Cytokine Receptor Association Modulates Synthetic Agonist Signaling.bioRxiv : the preprint server for biology · 2025Article
- An asymmetric tetrabody is a potent and efficacious agonist of the erythropoietin receptor in vitro and in vivo.Protein science : a publication of the Protein Society · 2025Article
- Structure-Guided Stapling of Dimeric Conformations and Linker Engineering Enhance Thermostability and Fine-Tune Activity of Bispecific VHH Cytokine Agonists.Antibodies (Basel, Switzerland) · 2025Article
- Engineering synthetic signaling receptors to enable erythropoietin-free erythropoiesis.Nature communications · 2025Article
- Structural studies of the IFNλ4 receptor complex using cryoEM enabled by protein engineering.Nature communications · 2025Article
- The JAK-STAT pathway: from structural biology to cytokine engineering.Signal transduction and targeted therapy · 2024Review
- Article
- i-shaped antibody engineering enables conformational tuning of biotherapeutic receptor agonists.Nature communications · 2024Article
- Location, location, location: Protein kinase nanoclustering for optimised signalling output.eLife · 2024Review
- Phenotypic screening of signaling motifs that efficiently induce cell proliferation.Scientific reports · 2023Article
47 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
19 authors at 8 institutions in 5 countries.
Funding
Abstract
Most cell-surface receptors for cytokines and growth factors signal as dimers, but it is unclear whether remodeling receptor dimer topology is a viable strategy to "tune" signaling output. We utilized diabodies (DA) as surrogate ligands in a prototypical dimeric receptor-ligand system, the cytokine Erythropoietin (EPO) and its receptor (EpoR), to dimerize EpoR ectodomains in non-native architectures. Diabody-induced signaling amplitudes varied from full to minimal agonism, and structures of these DA/EpoR complexes differed in EpoR dimer orientation and proximity. Diabodies also elicited biased or differential activation of signaling pathways and gene expression profiles compared to EPO. Non-signaling diabodies inhibited proliferation of erythroid precursors from patients with a myeloproliferative neoplasm due to a constitutively active JAK2V617F mutation. Thus, intracellular oncogenic mutations causing ligand-independent receptor activation can be counteracted by extracellular ligands that re-orient receptors into inactive dimer topologies. This approach has broad applications for tuning signaling output for many dimeric receptor systems.
Indexed as
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What Socratic holds
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 Socratic graph.