ArticleBiochimica et biophysica acta. Molecular cell research2020
JAK2 regulates Nav1.6 channel function via FGF14
Article in Biochimica et biophysica acta. Molecular cell research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 19 papers.
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Who cites it
19 citing papers in PubMed, 28 citations in OpenAlex.
- In Vivo Expression of an SCA27A-LinkedThe Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- Fedratinib in chronic kidney disease: antifibrotic potential and renal safety signals from integrated network toxicology and pharmacovigilance.Renal failure · 2025Article
- FGF14 Peptide Derivative Differentially Regulates Nav1.2 and NaLife (Basel, Switzerland) · 2025Article
- Sensory neuron-expressed FGF13 controls nociceptive signaling in diabetic neuropathy models.The Journal of clinical investigation · 2025Article
- Inhibition of the GSK3β/Nav1.6 complex suppresses early-stage Alzheimer's hyperexcitability.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Article
- Enhanced motivated behavior mediated by pharmacological targeting of the FGF14/NaNature communications · 2025Article
- Obesity Arrhythmias: Role of IL-6 Trans-Signaling.International journal of molecular sciences · 2024Review
- Crosstalk among WEE1 Kinase, AKT, and GSK3 in Nav1.2 Channelosome Regulation.International journal of molecular sciences · 2024Article
- TNFR1 signaling converging on FGF14 controls neuronal hyperactivity and sickness behavior in experimental cerebral malaria.Journal of neuroinflammation · 2023Article
- Determinants of iFGF13-mediated regulation of myocardial voltage-gated sodium (NaV) channels in mouse.The Journal of general physiology · 2023Article
- Voltage-Gated NaLife (Basel, Switzerland) · 2023Review
- FGF12 is a novel component of the nucleolar NOLC1/TCOF1 ribosome biogenesis complex.Cell communication and signaling : CCS · 2022Article
- Glycogen Synthase Kinase 3: Ion Channels, Plasticity, and Diseases.International journal of molecular sciences · 2022Review
- Inhibition of the Akt/PKB Kinase Increases NaInternational journal of molecular sciences · 2022Article
- Pharmacologically Targeting the Fibroblast Growth Factor 14 Interaction Site on the Voltage-Gated NaInternational journal of molecular sciences · 2021Article
- Article
- Differential Modulation of the Voltage-Gated NaFrontiers in molecular biosciences · 2021Article
- Inhibition of AKT Signaling Alters βIV Spectrin Distribution at the AIS and Increases Neuronal Excitability.Frontiers in molecular neuroscience · 2021Article
- Design, Synthesis, and Pharmacological Evaluation of Analogues Derived from the PLEV Tetrapeptide as Protein-Protein Interaction Modulators of Voltage-Gated Sodium Channel 1.6.Journal of medicinal chemistry · 2020Article
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Authors and funding
8 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundProtein interactions between voltage-gated sodium (Nav) channels and accessory proteins play an essential role in neuronal firing and plasticity. However, a surprisingly limited number of kinases have been identified as regulators of these molecular complexes. We hypothesized that numerous as-of-yet unidentified kinases indirectly regulate the Nav channel via modulation of the intracellular fibroblast growth factor 14 (FGF14), an accessory protein with numerous unexplored phosphomotifs and required for channel function in neurons.
methodsHere we present results from an in-cell high-throughput screening (HTS) against the FGF14: Nav1.6 complex using >3000 diverse compounds targeting an extensive range of signaling pathways. Regulation by top kinase targets was then explored using in vitro phosphorylation, biophysics, mass-spectrometry and patch-clamp electrophysiology.
resultsCompounds targeting Janus kinase 2 (JAK2) were over-represented among HTS hits. Phosphomotif scans supported by mass spectrometry revealed FGF14
conclusionsThese studies point toward a novel mechanism by which levels of JAK2 in neurons could directly influence firing and plasticity by controlling the FGF14 dimerization equilibrium, and thereby the availability of monomeric species for interaction with Nav1.6.
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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 Socratic graph.