ArticleeLife2021
Competitive binding of STATs to receptor phospho-Tyr motifs accounts for altered cytokine responses.
Article in eLife, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 28 citations in OpenAlex.
- Real-time visualization of STAT activation in live cells using genetically encoded biosensors.Nature chemical biology · 2026Article
- IL-27: A Double-Edged Sword in Immune Regulation via JAK-STAT Orchestration.Journal of immunology research · 2026Review
- Traditional Chinese Medicine for Diabetic Sarcopenia: A Review and Its Related Mechanisms.Journal of diabetes research · 2026Review
- Gut microbiota-derived metabolites and IL-22 signaling in inflammatory bowel disease: context-dependent regulation of mucosal repair and inflammation.Frontiers in immunology · 2026Review
- Deciphering the mechanisms and effects of hyperglycemia on skeletal muscle atrophy.Metabolism open · 2024Review
- Research on the signaling pathway and the related mechanism of traditional Chinese medicine intervention in chronic gastritis of the "inflammation-cancer transformation".Frontiers in pharmacology · 2024Review
- Network Pharmacology, Molecular Docking, and Molecular Dynamics Simulation to Elucidate the Molecular Targets and Potential Mechanism ofPathogens (Basel, Switzerland) · 2023Article
- Cytokine receptor IL27RA is an NF-κB-responsive gene involved in CD38 upregulation in multiple myeloma.Blood advances · 2023Article
- Th1 Cells Alter the Inflammatory Signature of IL-6 by Channeling STAT Transcription Factors to Alu-like Retroelements.Journal of immunology (Baltimore, Md. : 1950) · 2023Article
- Molecular and cellular factors determining the functional pleiotropy of cytokines.The FEBS journal · 2023Review
- Structural insights into the assembly and activation of the IL-27 signaling complex.EMBO reports · 2022Article
- Article
- Making sense of IL-6 signalling cues in pathophysiology.FEBS letters · 2022Review
- Dissecting the dynamic transcriptional landscape of early T helper cell differentiation into Th1, Th2, and Th1/2 hybrid cells.Frontiers in immunology · 2022Article
- Mettl3 promotes oxLDL-mediated inflammation through activating STAT1 signaling.Journal of clinical laboratory analysis · 2022Article
- Competitive binding of STATs to receptor phospho-Tyr motifs accounts for altered cytokine responses.eLife · 2021Article
Corrections and comments
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Authors and funding
16 authors at 5 institutions in 4 countries.
Funding
Abstract
Cytokines elicit pleiotropic and non-redundant activities despite strong overlap in their usage of receptors, JAKs and STATs molecules. We use IL-6 and IL-27 to ask how two cytokines activating the same signaling pathway have different biological roles. We found that IL-27 induces more sustained STAT1 phosphorylation than IL-6, with the two cytokines inducing comparable levels of STAT3 phosphorylation. Mathematical and statistical modeling of IL-6 and IL-27 signaling identified STAT3 binding to GP130, and STAT1 binding to IL-27Rα, as the main dynamical processes contributing to sustained pSTAT1 levels by IL-27. Mutation of Tyr613 on IL-27Rα decreased IL-27-induced STAT1 phosphorylation by 80% but had limited effect on STAT3 phosphorgylation. Strong receptor/STAT coupling by IL-27 initiated a unique gene expression program, which required sustained STAT1 phosphorylation and IRF1 expression and was enriched in classical Interferon Stimulated Genes. Interestingly, the STAT/receptor coupling exhibited by IL-6/IL-27 was altered in patients with systemic lupus erythematosus (SLE). IL-6/IL-27 induced a more potent STAT1 activation in SLE patients than in healthy controls, which correlated with higher STAT1 expression in these patients. Partial inhibition of JAK activation by sub-saturating doses of Tofacitinib specifically lowered the levels of STAT1 activation by IL-6. Our data show that receptor and STATs concentrations critically contribute to shape cytokine responses and generate functional pleiotropy in health and disease.
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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.