ArticleScience advances2024
Molecular basis of JAK2 activation in erythropoietin receptor and pathogenic JAK2 signaling.
Article in Science advances, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 11 papers.
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
11 citing papers in PubMed, 20 citations in OpenAlex.
- [Emphasis on the etiological diagnosis and management of non-cirrhotic portal hypertension].Zhonghua gan zang bing za zhi = Zhonghua ganzangbing zazhi = Chinese journal of hepatology · 2026Review
- Genomic insights transform diagnosis, prognosis, and therapy in BCR::ABL1-negative myeloproliferative neoplasms.International journal of hematology · 2026Review
- Pharmacological targeting of the JAK-STAT pathway: new concepts and emerging indications.Nature reviews. Drug discovery · 2026Review
- Heritability and Transcriptional Impact of JAK3, STAT5A and STAT6 Variants in a Tyrolean Family.International journal of molecular sciences · 2026Article
- GPR4 promotes immune exclusion in colon cancer through LOXL2-mediated extracellular matrix remodeling.Nature communications · 2025Article
- Advances in the characterization of in vitro-generated red blood cells: from biophysical properties to functional applications.Stem cell research & therapy · 2025Review
- JAK2 46/1 (GGCC) Haplotype in Oncogenesis, as Risk Stratifier, and Indicator for Drug Resistance in Myeloproliferative Neoplasms.International journal of molecular sciences · 2025Review
- Targeting JAK2 with a multifunctional nanoinhibitor for long-lasting anti-inflammatory effects and bone repair.Journal of nanobiotechnology · 2025Article
- Single-molecule tweezers decode hidden dimerization patterns of membrane proteins within lipid bilayers.Nature communications · 2025Article
- Impact of Ruxolitinib Interactions on JAK2 JH1 Domain Dynamics.International journal of molecular sciences · 2025Article
- Analysis of adverse events with ruxolitinib using real-world datasets and drug-interaction networks.SAGE open medicine · 2025Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
11 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Janus kinase 2 (JAK2) mediates type I/II cytokine receptor signaling, but JAK2 is also activated by somatic mutations that cause hematological malignancies by mechanisms that are still incompletely understood. Quantitative superresolution microscopy (qSMLM) showed that erythropoietin receptor (EpoR) exists as monomers and dimerizes upon Epo stimulation or through the predominant JAK2 pseudokinase domain mutations (V617F, K539L, and R683S). Crystallographic analysis complemented by kinase activity analysis and atomic-level simulations revealed distinct pseudokinase dimer interfaces and activation mechanisms for the mutants: JAK V617F activity is driven by dimerization, K539L involves both increased receptor dimerization and kinase activity, and R683S prevents autoinhibition and increases catalytic activity and drives JAK2 equilibrium toward activation state through a wild-type dimer interface. Artificial intelligence-guided modeling and simulations revealed that the pseudokinase mutations cause differences in the pathogenic full-length JAK2 dimers, particularly in the FERM-SH2 domains. A detailed molecular understanding of mutation-driven JAK2 hyperactivation may enable novel therapeutic approaches to selectively target pathogenic JAK2 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.