ArticleNature structural & molecular biology2014
Molecular basis for pseudokinase-dependent autoinhibition of JAK2 tyrosine kinase.
Article in Nature structural & molecular biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 81 papers.
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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.
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Who cites it
81 citing papers in PubMed, 160 citations in OpenAlex.
- Review
- Targeting DESI2 as a Novel Therapeutic Strategy for JAK2-Mutant Leukemias.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- In silico modeling guides identification of novel JAK1 variants associated with immune dysregulation.EMBO molecular medicine · 2025Article
- Reaction Coordinates Are Optimal Channels of Energy Flow.Annual review of physical chemistry · 2025Review
- Enhanced sampling of protein conformational changes via true reaction coordinates from energy relaxation.Nature communications · 2025Article
- Deep learning-guided discovery of selective JAK2-JH2 allosteric inhibitors: integration of MLP predictive modeling, BREED-based library design, and computational validation.Frontiers in chemistry · 2025Article
- JAK inhibitor selectivity: new opportunities, better drugs?Nature reviews. Rheumatology · 2024Review
- Co-targeting JAK1/STAT6/GAS6/TAM signaling improves chemotherapy efficacy in Ewing sarcoma.Nature communications · 2024Article
- Tyrosine phosphorylation of CARM1 promotes its enzymatic activity and alters its target specificity.Nature communications · 2024Article
- Molecular basis of JAK2 activation in erythropoietin receptor and pathogenic JAK2 signaling.Science advances · 2024Article
- JAK-STAT signaling in inflammation and stress-related diseases: implications for therapeutic interventions.Molecular biomedicine · 2023Review
- Structural basis of Janus kinase trans-activation.Cell reports · 2023Article
- Allosteric regulation and inhibition of protein kinases.Biochemical Society transactions · 2023Review
- Identification of Novel Small Molecule Ligands for JAK2 Pseudokinase Domain.Pharmaceuticals (Basel, Switzerland) · 2023Article
- Regulation of the JAK/STAT signaling pathway in spinal cord injury: an updated review.Frontiers in immunology · 2023Review
- Selective inhibitors of JAK1 targeting an isoform-restricted allosteric cysteine.Nature chemical biology · 2022Article
- Identification of Altered Primary Immunodeficiency-Associated Genes and Their Implications in Pediatric Cancers.Cancers · 2022Article
- Looking lively: emerging principles of pseudokinase signaling.Trends in biochemical sciences · 2022Review
- Structure of a Janus kinase cytokine receptor complex reveals the basis for dimeric activation.Science (New York, N.Y.) · 2022Article
- 501Y.V2 spike protein resists the neutralizing antibody in atomistic simulations.Computational biology and chemistry · 2022Article
21 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
9 authors at 6 institutions in 3 countries.
Funding
Abstract
Janus kinase-2 (JAK2) mediates signaling by various cytokines, including erythropoietin and growth hormone. JAK2 possesses tandem pseudokinase and tyrosine-kinase domains. Mutations in the pseudokinase domain are causally linked to myeloproliferative neoplasms (MPNs) in humans. The structure of the JAK2 tandem kinase domains is unknown, and therefore the molecular bases for pseudokinase-mediated autoinhibition and pathogenic activation remain obscure. Using molecular dynamics simulations of protein-protein docking, we produced a structural model for the autoinhibitory interaction between the JAK2 pseudokinase and kinase domains. A striking feature of our model, which is supported by mutagenesis experiments, is that nearly all of the disease mutations map to the domain interface. The simulations indicate that the kinase domain is stabilized in an inactive state by the pseudokinase domain, and they offer a molecular rationale for the hyperactivity of V617F, the predominant JAK2 MPN mutation.
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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.