ArticleMolecular biology of the cell2016
Defining the functional binding sites of interleukin 12 receptor β1 and interleukin 23 receptor to Janus kinases.
Article in Molecular biology of the cell, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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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
30 citing papers in PubMed, 48 citations in OpenAlex.
- First-in-human study of deucravacitinib: A selective, potent, allosteric small-molecule inhibitor of tyrosine kinase 2.Clinical and translational science · 2023Trial
- Receptor engineering constitutes feedback control and robustness of IL-23R signaling and highlights importance of intracellular cytokine receptor signaling motifs.Cell communication and signaling : CCS · 2026Article
- Tyrosine kinase 2 inhibitors in the therapy of inflammatory and autoimmune diseases.Pharmacological reports : PR · 2025Review
- JAK inhibition and axial spondyloarthritis: new steps on the path to understanding pathophysiology.Frontiers in immunology · 2025Review
- Exploration of JAK/STAT pathway activation in ulcerative colitis reveals sex-dependent activation of JAK2/STAT3 in the inflammatory response.Frontiers in immunology · 2025Observational
- The IL-23R and Its Genetic Variants: A Hitherto Unforeseen Bridge Between the Immune System and Cancer Development.Cancers · 2024Review
- Unconventional Activation of IRE1 Enhances Th17 Responses and Promotes Airway Neutrophilia.American journal of respiratory cell and molecular biology · 2024Article
- Targeting TYK2 for Fighting Diseases: Recent Advance of TYK2 Inhibitors.Current medicinal chemistry · 2024Review
- Inhibition of JAK1,2 Prevents Fibrotic Remodeling of Pulmonary Vascular Bed and Improves Outcomes in the Rat Model of Chronic Thromboembolic Pulmonary Hypertension.International journal of molecular sciences · 2022Article
- Cytokines in Abdominal Aortic Aneurysm: Master Regulators With Clinical Application.Biomarker insights · 2022Review
- The Framework for Human Host Immune Responses to Four Types of Parasitic Infections and Relevant Key JAK/STAT Signaling.International journal of molecular sciences · 2021Review
- Inverse behavior of IL-23R and IL-17RA in chronic and aggressive periodontitis.Journal of periodontal & implant science · 2021Article
- The Many Faces of JAKs and STATs Within the COVID-19 Storm.Frontiers in immunology · 2021Review
- JAK/STAT-Dependent Chimeric Antigen Receptor (CAR) Expression: A Design Benefiting From a Dual AND/OR Gate Aiming to Increase Specificity, Reduce Tumor Escape and Affect Tumor Microenvironment.Frontiers in immunology · 2021Article
- JAK/STAT Activation: A General Mechanism for Bone Development, Homeostasis, and Regeneration.International journal of molecular sciences · 2020Review
- IL-12 and IL-23-Close Relatives with Structural Homologies but Distinct Immunological Functions.Cells · 2020Review
- Review
- Synthetic interleukin 22 (IL-22) signaling reveals biological activity of homodimeric IL-10 receptor 2 and functional cross-talk with the IL-6 receptor gp130.The Journal of biological chemistry · 2020Article
- Deciphering site 3 interactions of interleukin 12 and interleukin 23 with their cognate murine and human receptors.The Journal of biological chemistry · 2020Article
- TYK2 inhibition reduces type 3 immunity and modifies disease progression in murine spondyloarthritis.The Journal of clinical investigation · 2020Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 2 countries.
Funding
Abstract
The interleukin (IL)-12-type cytokines IL-12 and IL-23 are involved in T-helper (Th) 1 and Th17 immunity, respectively. They share the IL-12 receptor β1 (IL-12Rβ1) as one component of their receptor signaling complexes, with IL-12Rβ2 as second receptor for IL-12 and IL-23R for IL-23 signal transduction. Stimulation with IL-12 and IL-23 results in activation of receptor-associated Janus kinases (Jak) and phosphorylation of STAT proteins in target cells. The Janus kinase tyrosine kinase (Tyk) 2 associates with IL-12Rβ1, whereas Jak2 binds to IL-23R and also to IL-12Rβ2. Receptor association of Jak2 is mediated by Box1 and Box2 motifs located within the intracellular domain of the receptor chains. Here we define the Box1 and Box2 motifs in IL-12Rβ1 and an unusual Jak2-binding site in IL-23R by the use of deletion and site-directed mutagenesis. Our data show that nonfunctional box motifs abolish IL-12- and IL-23-induced STAT3 phosphorylation and cytokine-dependent proliferation of Ba/F3 cells. Coimmunoprecipitation of Tyk2 by IL-12Rβ1 and Jak2 by IL‑23R supported these findings. In addition, our data demonstrate that association of Jak2 with IL-23R is mandatory for IL-12 and/or IL-23 signaling, whereas Tyk2 seems to be dispensable.
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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.