ArticleScience signaling2015
Instructive roles for cytokine-receptor binding parameters in determining signaling and functional potency.
Article in Science signaling, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
42 citing papers in PubMed, 68 citations in OpenAlex.
- Multi-dimensional orchestration of binders for improved CAR-T immunotherapy.Cancer letters · 2026Review
- A dual-pathway Wnt-IL-13 fusion protein enhances human intestinal regeneration through tuft cell activation.The Journal of biological chemistry · 2026Article
- De Novo Design and Directed Evolution Refinement of Mirror-Image Protein Binders Targeting Interleukin-4.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Differential Effect of Cytokines on CD4+ T-Cell Activation, Metabolism, and Susceptibility to HIV-1 Infection.Journal of immunology research · 2026Article
- Article
- Type II Interleukin-4 Receptor Activation in Basal Breast Cancer Cells Promotes Tumor Progression via Metabolic and Epigenetic Modulation.International journal of molecular sciences · 2024Article
- SpyMask enables combinatorial assembly of bispecific binders.Nature communications · 2024Article
- Design of cell-type-specific hyperstable IL-4 mimetics via modular de novo scaffolds.Nature chemical biology · 2023Article
- Molecular and cellular factors determining the functional pleiotropy of cytokines.The FEBS journal · 2023Review
- Insights into receptor structure and dynamics at the surface of living cells.Nature communications · 2023Article
- Structural insights into the assembly of gp130 family cytokine signaling complexes.Science advances · 2023Article
- Proximity-enabled covalent binding of IL-2 to IL-2Rα selectively activates regulatory T cells and suppresses autoimmunity.Signal transduction and targeted therapy · 2023Article
- Emerging principles of cytokine pharmacology and therapeutics.Nature reviews. Drug discovery · 2023Review
- Structure and dynamics of Toll immunoreceptor activation in the mosquito Aedes aegypti.Nature communications · 2022Article
- Engineered IL13 variants direct specificity of IL13Rα2-targeted CAR T cell therapy.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Loss of Interleukin-13-Receptor-Alpha-1 Induces Apoptosis and Promotes EMT in Pancreatic Cancer.International journal of molecular sciences · 2022Article
- Rational design of heterodimeric receptors capable of activating target signaling molecules.Scientific reports · 2021Article
- The discriminatory power of the T cell receptor.eLife · 2021Article
- Competitive binding of STATs to receptor phospho-Tyr motifs accounts for altered cytokine responses.eLife · 2021Article
- Involvement of IL-4, IL-13 and Their Receptors in Pancreatic Cancer.International journal of molecular sciences · 2021Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 1 institution in 1 country.
Funding
Abstract
Cytokines dimerize cell surface receptors to activate signaling and regulate many facets of the immune response. Many cytokines have pleiotropic effects, inducing a spectrum of redundant and distinct effects on different cell types. This pleiotropy has hampered cytokine-based therapies, and the high doses required for treatment often lead to off-target effects, highlighting the need for a more detailed understanding of the parameters controlling cytokine-induced signaling and bioactivities. Using the prototypical cytokine interleukin-13 (IL-13), we explored the interrelationships between receptor binding and a wide range of downstream cellular responses. We applied structure-based engineering to generate IL-13 variants that covered a spectrum of binding strengths for the receptor subunit IL-13Rα1. Engineered IL-13 variants representing a broad range of affinities for the receptor exhibited similar potencies in stimulating the phosphorylation of STAT6 (signal transducer and activator of transcription 6). Delays in the phosphorylation and nuclear translocation of STAT6 were only apparent for those IL-13 variants with markedly reduced affinities for the receptor. From these data, we developed a mechanistic model that quantitatively reproduced the kinetics of STAT6 phosphorylation for the entire spectrum of binding affinities. Receptor endocytosis played a key role in modulating STAT6 activation, whereas the lifetime of receptor-ligand complexes at the plasma membrane determined the potency of the variant for inducing more distal responses. This complex interrelationship between extracellular ligand binding and receptor function provides the foundation for new mechanism-based strategies that determine the optimal cytokine dose to enhance therapeutic efficacy.
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What OpenQuestion 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 OpenQuestion graph.