ArticleScience (New York, N.Y.)2022
Structure of a Janus kinase cytokine receptor complex reveals the basis for dimeric activation.
Article in Science (New York, N.Y.), 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 98 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
98 citing papers in PubMed, 1 synthesis or guideline pooled it, 163 citations in OpenAlex.
- Individuals with JAK1 variants are affected by syndromic features encompassing autoimmunity, atopy, colitis, and dermatitis.The Journal of experimental medicine · 2024Pooled it
- Pharmacokinetics and safety of SHR0302, a selective JAK1 inhibitor, in Chinese patients with hepatic impairment.Frontiers in pharmacology · 2026Trial
- Modulating pseudokinase conformation from the ATP-binding site.Structure (London, England : 1993) · 2026Article
- PI3K/AKT signaling pathway: molecular crossroads in tumorigenesis and therapeutic innovation.Signal transduction and targeted therapy · 2026Review
- Joined Signatures of Erythropoietin and Interleukin-6 Signaling by Synthetic Heterodimeric gp130:Epo Receptor Complexes.ACS synthetic biology · 2026Article
- Deep mutational scanning reveals pharmacologically relevant insights into TYK2 signaling and disease.eLife · 2026Article
- What is the future of acromegaly therapy?The Journal of clinical endocrinology and metabolism · 2026Review
- Emerging landscape of oncogenic signaling pathways in cervical cancer.Discover oncology · 2026Review
- Design, synthesis, and activity study of heterocyclic derivatives as JAK inhibitors.Medicinal chemistry research : an international journal for rapid communications on design and mechanisms of action of biologically active agents · 2026Article
- JAK-STAT signaling pathway in cancer: from molecular mechanisms to clinical intervention.Molecular cancer · 2026Review
- Article
- Psoriatic Arthritis: Therapeutic Advances and Novel Treatment Strategies-A Scoping Review.Life (Basel, Switzerland) · 2026Review
- Membrane-Based Assembly and Interactions in Immune Receptors.Chemical reviews · 2026Review
- JAK/STAT signaling in liver disease: a therapeutic target or a context-dependent double-edged sword?Journal of translational medicine · 2026Review
- Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications.Nature reviews. Drug discovery · 2026Review
- Function-driven design of a surrogate interleukin-2 receptor ligand.FEBS letters · 2026Article
- Targeting JAK/STAT signalling with cold atmospheric plasma: a potential therapy for systemic lupus erythematosus.Expert reviews in molecular medicine · 2026Review
- Revisiting Janus kinases as molecular drug targets for rheumatic diseases.Frontiers in medicine · 2026Review
- Mechanisms of Differential Signal Transduction by Interferon Lambda Receptor 1 Variants.Journal of innate immunity · 2026Article
- The Th17/Treg axis: a key to understanding and treating autoimmune disorders.Open life sciences · 2026Article
38 more citing papers are in PubMed but not listed here.
Corrections and comments
- Commented on by
Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Cytokines signal through cell surface receptor dimers to initiate activation of intracellular Janus kinases (JAKs). We report the 3.6-angstrom-resolution cryo-electron microscopy structure of full-length JAK1 complexed with a cytokine receptor intracellular domain Box1 and Box2 regions captured as an activated homodimer bearing the valine→phenylalanine (VF) mutation prevalent in myeloproliferative neoplasms. The seven domains of JAK1 form an extended structural unit, the dimerization of which is mediated by close-packing of the pseudokinase (PK) domains from the monomeric subunits. The oncogenic VF mutation lies within the core of the JAK1 PK interdimer interface, enhancing packing complementarity to facilitate ligand-independent activation. The carboxy-terminal tyrosine kinase domains are poised for transactivation and to phosphorylate the receptor STAT (signal transducer and activator of transcription)-recruiting motifs projecting from the overhanging FERM (four-point-one, ezrin, radixin, moesin)-SH2 (Src homology 2)-domains. Mapping of constitutively active JAK mutants supports a two-step allosteric activation mechanism and reveals opportunities for selective therapeutic targeting of oncogenic JAK signaling.
Indexed as
Identifiers
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.