Affinage

MAPK10

Mitogen-activated protein kinase 10 · UniProt P53779

Length
464 aa
Mass
52.6 kDa
Annotated
2026-06-10
100 papers in source corpus 39 papers cited in narrative 39 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/8 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAPK10/JNK3 is a neuronally enriched stress-activated MAP kinase that serves as a central effector of neuronal apoptosis and degeneration, acting upstream of c-Jun/AP-1 transcriptional activation in excitotoxic and trophic-deprivation death pathways (PMID:9349820, PMID:11461965). It is fully activated by dual phosphorylation: MKK7 catalyzes the rate-limiting Thr-221 monophosphorylation (~100-fold faster than MKK4-mediated Tyr-223 phosphorylation) sufficient for measurable activity, while bisphosphorylation by MKK4 plus MKK7 maximizes catalysis (PMID:10715136, PMID:30591558), a configuration rationalized by structures showing the unphosphorylated enzyme adopts an open, catalytically misaligned conformation (PMID:9739089). Arrestin-3/beta-arrestin 2 scaffolds the ASK1–MKK4/7–JNK3 module through a defined C-terminal element, preferentially binding inactive JNK3 and releasing it upon activation in a 'conveyor belt' amplification mechanism that drives receptor-coupled signaling and cytosolic retention (PMID:11090355, PMID:21715332, PMID:23960075, PMID:30591558). JNK3 phosphorylates a broad neuronal substrate set—c-Jun and ATF-2 (PMID:12401814), p53 at Ser34 (PMID:9393873), APP at Thr668 (PMID:15944381), SCG10 at Ser62/73 (PMID:11718727), kinesin-1 (PMID:19525941), Mcl-1 at Ser121 (PMID:17670986), PSD-95 (PMID:23329067), and KLF9 at Ser106/110 (PMID:28871032)—coupling it to apoptosis (Bim/Fas induction and cytochrome c release (PMID:14657393), mitochondrial ceramide synthase activation (PMID:17609208)), impaired axonal transport (PMID:19525941), synaptic signaling (PMID:23329067), and suppression of axon regeneration (PMID:28871032). Through a feed-forward loop, JNK3 phosphorylation of APP-T668 promotes amyloidogenic processing in Alzheimer models (PMID:22958823), while AICD transcriptionally upregulates the JNK3 locus after axonal injury (PMID:29238071). Beyond canonical kinase signaling, palmitoylation directs JNK3 to the Golgi where it binds the phosphatase Sac1 to deplete PI4P and inhibit secretory trafficking (PMID:23838184), and couples it to DLK on axonal vesicles in a positive-feedback module driving retrograde prodegenerative signaling (PMID:35349303). In non-neuronal contexts JNK3 acts through a DLK–JNK3–cyclin D axis to promote postnatal beta-cell replication and maintains IRS2–Akt2 pro-survival signaling (PMID:32189007, PMID:22563476). A zebrafish loss-of-function study links mapk10 to enteric nervous system development as a Hirschsprung disease modifier (PMID:27902697), and truncated JNK3 variants that cannot phosphorylate c-Jun or PSD-95 are associated with intellectual disability (PMID:23329067).

Mechanistic history

Synthesis pass · year-by-year structured walk · 38 steps
  1. 1995 Medium

    Established JNK3 as a nervous-system-restricted MAP kinase capable of dual Thr/Tyr autophosphorylation, defining it as a distinct neuronal stress kinase.

    Evidence in vitro autophosphorylation, cDNA characterization, and tissue expression by Northern/immunochemistry

    PMID:7826642

    Open questions at the time
    • No upstream activators or physiological substrates identified
    • Function in vivo not addressed
  2. 1997 High

    Demonstrated that JNK3 is genetically required for excitotoxic neuronal apoptosis, placing it upstream of c-Jun/AP-1 in the death pathway and establishing its disease relevance.

    Evidence Jnk3 germline knockout mice in a kainic acid excitotoxicity model with c-Jun phosphorylation and AP-1 reporter readouts

    PMID:9349820

    Open questions at the time
    • Direct substrate phosphorylation by JNK3 not shown biochemically
    • Mechanism of JNK3 activation not addressed
  3. 1997 Medium

    Showed JNK3 can phosphorylate p53 at Ser34 and associate with it, expanding the candidate substrate repertoire toward apoptotic regulators.

    Evidence in vitro kinase assay, dominant-negative mutant, and Co-IP in 293T cells

    PMID:9393873

    Open questions at the time
    • Finding shared across JNK1/2/3, not JNK3-specific
    • In vivo relevance of p53-Ser34 phosphorylation by JNK3 untested
  4. 1998 High

    Provided the structural basis for JNK3's low basal activity and ATP-binding architecture, explaining why dual phosphorylation is required for activation.

    Evidence X-ray crystallography of unphosphorylated JNK3 with an ATP analog

    PMID:9739089

    Open questions at the time
    • No structure of the activated/bisphosphorylated enzyme
    • Substrate-bound conformation not resolved
  5. 2000 High

    Defined the dual-kinase activation logic, showing MKK7 monophosphorylation of Thr is sufficient for activity while MKK4+MKK7 bisphosphorylation maximizes catalysis.

    Evidence in vitro reconstitution with purified MKK4/MKK7/JNK3, mass spectrometry site mapping, and steady-state kinetics

    PMID:10715136

    Open questions at the time
    • Cellular regulation of MKK4 vs MKK7 input not addressed
    • Role of scaffolds in vivo not established here
  6. 2000 High

    Identified beta-arrestin 2 as a direct JNK3 scaffold linking GPCR signaling to the ASK1–MKK4–JNK3 module and controlling JNK3 subcellular localization.

    Evidence yeast two-hybrid, reciprocal Co-IP from brain and COS-7 cells, confocal co-localization, and kinase assays with AT1A receptor stimulation

    PMID:11090355

    Open questions at the time
    • Scaffold-binding residues not yet mapped
    • Quantitative effect on activation kinetics unresolved
  7. 2001 High

    Mapped the arrestin-3 RRSLHL docking motif and showed it enhances the specific MKK4→JNK3 phosphorylation step, defining the scaffold mechanism at residue resolution.

    Evidence arrestin chimeras, site-directed mutagenesis, Co-IP, and JNK3 phosphorylation assays

    PMID:11356842

    Open questions at the time
    • MKK7 contribution to the scaffold not addressed here
    • In vivo requirement of the motif untested
  8. 2001 High

    Identified SCG10 as a direct neuronal substrate phosphorylated at Ser62/73, linking JNK3 to microtubule dynamics during trophic deprivation.

    Evidence in vitro kinase assay with site mapping, microtubule destabilization assay, Co-IP, and NGF-deprivation neuron model

    PMID:11718727

    Open questions at the time
    • Functional consequence for axon morphology in vivo not shown
    • JNK3 isoform specificity for SCG10 not tested
  9. 2001 High

    Placed JNK3 specifically in the c-Jun activation branch of NGF-deprivation apoptosis, distinct from ROS generation.

    Evidence sympathetic neurons from Jnk3 KO mice with c-Jun phosphorylation, c-jun mRNA, oxidative stress, and apoptosis readouts

    PMID:11461965

    Open questions at the time
    • Direct JNK3-c-Jun phosphorylation in these neurons not isolated from other JNKs
    • Mechanism upstream of JNK3 activation unaddressed
  10. 2002 Medium

    Showed context-dependent substrate choice (ATF-2 in death vs c-Jun in differentiation), indicating JNK3 outputs depend on stimulus.

    Evidence JNK3 gain-of-function in JNK3-null PC12 cells with substrate phosphorylation and neurite outgrowth readouts

    PMID:12401814

    Open questions at the time
    • Molecular basis for substrate selectivity not defined
    • Single overexpression system
  11. 2002 Medium

    Implicated JNK3 in pathological tau phosphorylation and aggregation, connecting it to neurodegenerative proteinopathy.

    Evidence adenoviral co-expression of tau, MEKK, JNK3, GSK-3beta in COS-7 with phospho-epitope immunoblot, Thioflavin-S, and solubility assays

    PMID:12191990

    Open questions at the time
    • JNK3-specific contribution vs co-expressed kinases not isolated
    • No neuronal or in vivo validation
  12. 2003 High

    Defined the mitochondrial apoptotic effector arm of JNK3 in ischemia, via Bim/Fas induction and cytochrome c release.

    Evidence Jnk3 KO mice in cerebral ischemia-hypoxia model with JNK activity, Bim/Fas, and cytochrome c readouts

    PMID:14657393

    Open questions at the time
    • Direct JNK3 substrates linking to Bim/Fas not identified
    • Transcriptional vs post-translational control unresolved
  13. 2003 High

    Provided atomic-level basis for selective ATP-competitive JNK3 inhibition over related MAP kinases.

    Evidence X-ray crystallography of four JNK3-inhibitor complexes

    PMID:12954329

    Open questions at the time
    • No allosteric or substrate-site inhibition explored
    • Cellular efficacy not assessed in this work
  14. 2005 High

    Identified APP-Thr668 as a JNK3-isoform-specific substrate that physiologically limits APP/AICD nuclear signaling.

    Evidence primary neurons with isoform-selective siRNA/KO, APP-T668 immunoblot, AICD-Fe65 Co-IP, and nuclear localization assays

    PMID:15944381

    Open questions at the time
    • In vivo consequence for APP processing not addressed here
    • Upstream activator of JNK3 in differentiation unknown
  15. 2005 Medium

    Revealed dynamic scaffold-coupled phosphatase control, with MKP7 dissociation from beta-arrestin 2 enabling transient JNK3 activation after receptor stimulation.

    Evidence Co-IP of MKP7–beta-arrestin 2, JNK3 dephosphorylation assays, and AT1aR stimulation time course

    PMID:15888437

    Open questions at the time
    • Signal triggering MKP7 dissociation not defined
    • Single-lab biochemistry without in vivo confirmation
  16. 2006 Medium

    Showed that basal (receptor-unbound) arrestins pre-load JNK3 and exclude it from the nucleus, implying scaffold engagement precedes receptor activation.

    Evidence GFP-JNK3 nuclear exclusion assay in HEK293 with arrestin conformation mutants

    PMID:16737965

    Open questions at the time
    • Physiological relevance of nuclear exclusion to JNK3 signaling unclear
    • Overexpression-based localization readout
  17. 2007 High

    Defined the MyD88-5 adaptor as the route targeting JNK3 to mitochondria in ischemic death.

    Evidence reciprocal Co-IP, mitochondrial co-purification, MyD88-5 KO neurons, and oxygen-glucose deprivation model

    PMID:17724133

    Open questions at the time
    • JNK3 mitochondrial substrates not identified
    • Relationship to arrestin scaffolding unaddressed
  18. 2007 High

    Identified Mcl-1 Ser121 as a JNK3 substrate whose phosphorylation displaces Pin1 to promote Mcl-1 degradation and oligodendrocyte apoptosis after spinal cord injury.

    Evidence in vitro kinase assay, Pin1-Mcl-1 Co-IP, ubiquitination assay, and JNK3-/- vs Pin1-/- mice with cytochrome c readouts

    PMID:17670986

    Open questions at the time
    • Direct in vivo demonstration of Mcl-1 Ser121 phosphorylation by JNK3 limited
    • Generality across cell types untested
  19. 2007 High

    Linked JNK3 to mitochondrial ceramide synthase activation as a lipid-based mechanism of respiratory chain damage in ischemia/reperfusion.

    Evidence ceramide mass and synthase activity assays, mitochondrial fractionation, and JNK3-/- mice in IR model

    PMID:17609208

    Open questions at the time
    • Molecular target of JNK3 controlling ceramide synthase unknown
    • Post-translational mechanism not defined
  20. 2009 High

    Established a polyQ-huntingtin–JNK3–kinesin-1 axis that impairs fast axonal transport, mechanistically connecting JNK3 to Huntington disease.

    Evidence squid axoplasm FAT assay, HD models, JNK3 siRNA, MS substrate site identification, and kinesin-microtubule binding assay

    PMID:19525941

    Open questions at the time
    • Kinesin-1 phospho-site consequence in mammalian neurons in vivo not shown
    • Activation route of JNK3 by polyQ-Htt undefined
  21. 2009 High

    Uncovered a non-neuronal endothelial role: SDF-1alpha activates JNK3 via NO-dependent S-nitrosylation/inactivation of MKP7, driving cell migration.

    Evidence Co-IP, eNOS knockdown, S-nitrosylation and phosphatase assays, and migration assays

    PMID:19307591

    Open questions at the time
    • JNK3 substrates driving migration not identified
    • In vivo endothelial relevance not tested here
  22. 2011 Medium

    Mapped arrestin-3 residues (notably Val-343) required for JNK3 activation, showing scaffold catalysis is uncoupled from binding strength.

    Evidence arrestin chimeras/point mutants, Co-IP, and JNK3 phosphorylation assays

    PMID:21715332

    Open questions at the time
    • Structural basis of catalysis-vs-binding decoupling unresolved
    • In vivo significance of these residues untested
  23. 2011 High

    Placed JNK3 downstream of a PrPC–GluR6/7–PSD-95 signaling axis in excitotoxicity using genetic epistasis.

    Evidence Prnp/Jnk3 single and double KO mice, kainate model, pharmacological inhibition, and GluR6-PSD-95 Co-IP

    PMID:21757544

    Open questions at the time
    • Direct biochemical link from PSD-95 complex to JNK3 activation not defined
    • Receptor-proximal activation step unmapped
  24. 2012 High

    Defined a feed-forward Abeta42→JNK3→APP-T668 loop perpetuating amyloidogenesis, with JNK3 deletion reducing plaque load and improving cognition.

    Evidence JNK3-/- in FAD mice, translation blockade, APP-T668 immunoblot, Abeta42 ELISA, endocytosis assay, and behavioral testing

    PMID:22958823

    Open questions at the time
    • Direct in vivo demonstration of JNK3 catalysis on APP-T668 within the loop limited
    • Contribution of other JNKs not fully excluded
  25. 2012 Medium

    Revealed a JNK3-specific pro-survival role in beta cells via maintenance of IRS2–Akt2 signaling through FoxO3A.

    Evidence isoform-specific siRNA in INS-1E cells with IRS2/Akt2 immunoblot, FoxO3A activity, and c-Jun readouts

    PMID:22563476

    Open questions at the time
    • In vivo beta-cell survival role untested
    • Direct JNK3 substrates in this pathway not identified
  26. 2012 High

    Established JNK2/JNK3-JUN as the major axonal-injury death pathway in retinal ganglion cells via genetic epistasis.

    Evidence single and combined Jnk2/Jnk3 KO mice, optic nerve crush, JUN phosphorylation, and RGC survival counting

    PMID:22353563

    Open questions at the time
    • Distinct contributions of JNK2 vs JNK3 not resolved
    • Direct JUN phosphorylation by JNK3 not isolated
  27. 2013 High

    Discovered a palmitoylation-driven, kinase-activity-independent Golgi function whereby JNK3 binds Sac1 to deplete PI4P and inhibit secretory trafficking of GluR1.

    Evidence palmitoylation assays, kinase-dead and palmitoylation-deficient mutants, Golgi fractionation, Sac1 Co-IP, PI4P imaging, and GluR1 trafficking assays

    PMID:23838184

    Open questions at the time
    • In vivo significance of Golgi trafficking inhibition not established
    • Identity of the JNK3 palmitoyltransferase in vivo unconfirmed
  28. 2013 High

    Linked truncating JNK3 variants to intellectual disability and identified PSD-95/SAP102/SHANK3 as synaptic partners plus PSD-95 as a substrate.

    Evidence in vitro kinase assays (c-Jun, PSD-95) comparing wild-type vs disease mutants, Co-IP, Y2H, and synaptic immunofluorescence

    PMID:23329067

    Open questions at the time
    • Causality of variants via family/rescue not fully established
    • Functional consequence of PSD-95 phosphorylation in vivo untested
  29. 2013 High

    Showed arrestin-3 directly binds MKK7 in addition to MKK4 and JNK3, with concentration-dependent and ligand-state-dependent scaffold assembly.

    Evidence in vitro binding with purified proteins, cell Co-IP, and JNK3 phosphorylation assays

    PMID:23960075

    Open questions at the time
    • In vivo relevance of concentration-dependent scaffolding unknown
    • ASK1 incorporation kinetics not addressed
  30. 2015 High

    Defined a physiological developmental role: EphrinB2-STAT1 represses JNK3 to control endothelial death during hyaloid vessel pruning.

    Evidence Jnk3 KO mice, EphrinB2/STAT1 signaling constructs, and vascular imaging

    PMID:25807892

    Open questions at the time
    • Direct JNK3 substrates in endothelial apoptosis not identified
    • Molecular link from STAT1 to JNK3 repression unmapped
  31. 2016 Medium

    Identified a minimal 25-residue arrestin-3 element sufficient to bind MKK4/7 and ASK1 and enhance JNK3 activation, distinguishing it from arrestin-2.

    Evidence peptide binding assays with purified proteins and cellular JNK3 phosphorylation assays

    PMID:26868142

    Open questions at the time
    • Structural mechanism of peptide-mediated catalysis unresolved
    • Single-lab validation
  32. 2016 Medium

    Linked mapk10 to enteric nervous system development as a Hirschsprung disease modifier through interaction with ret.

    Evidence zebrafish mapk10 loss-of-function mutants with ret epistasis and ENS neuron imaging/counting

    PMID:27902697

    Open questions at the time
    • Mammalian/human ENS role not confirmed
    • Molecular pathway connecting MAPK10 to RET undefined
  33. 2017 High

    Defined JNK3 as a required effector of KLF9-mediated axon-growth suppression via phosphorylation at Ser106/110, with site mutation promoting regeneration.

    Evidence KLF9-JNK3 Co-IP, Ser106/110 mutagenesis, shRNA, neurite assays, and optic nerve crush regeneration in rats

    PMID:28871032

    Open questions at the time
    • Mechanism by which phospho-KLF9 suppresses transcription not detailed
    • Upstream JNK3 activation in this context unmapped
  34. 2017 High

    Established transcriptional autoregulation: AICD binds the JNK3 locus to upregulate its expression after axotomy, contributing to RGC death.

    Evidence ChIP at JNK3 locus, luciferase reporter, APP KO mice, gamma-secretase inhibitors, and RGC survival assays

    PMID:29238071

    Open questions at the time
    • Direct transcription-factor partners of AICD at the locus unresolved
    • Generalizability beyond optic nerve injury untested
  35. 2018 High

    Quantified the activation/release logic of the arrestin-3 scaffold, showing preferential binding of inactive JNK3, faster Thr-221 than Tyr-223 phosphorylation, and a 'conveyor belt' amplification requiring product release.

    Evidence binding affinity measurements, in vitro phosphorylation kinetics, and Bayesian systems-biochemistry modeling

    PMID:30591558

    Open questions at the time
    • In vivo validation of the conveyor-belt model lacking
    • Regulation of release rate by physiological cues unknown
  36. 2019 High

    Mapped the arrestin-3/JNK3 interface at structural resolution, identifying the arrestin-3 beta1 strand and ATP-status-dependent JNK3 C-lobe contacts.

    Evidence HDX-MS, 19F-NMR, fluorescence quenching, and C-terminal truncation mutants

    PMID:31080119

    Open questions at the time
    • No full co-complex crystal/cryo-EM structure
    • Single-lab biophysical characterization
  37. 2020 High

    Defined a non-neuronal proliferative role via a DLK–JNK3–cyclin D1/D2 axis required for postnatal beta-cell replication.

    Evidence DLK-JNK3 Co-IP, kinase activity assays, Dlk/Jnk3 siRNA in neonatal islets, cyclin expression, and replication quantification

    PMID:32189007

    Open questions at the time
    • Direct JNK3 substrate driving cyclin induction not identified
    • In vivo genetic confirmation in beta cells limited
  38. 2022 High

    Revealed a palmitoylation-dependent DLK-JNK3 positive-feedback module on axonal vesicles that drives retrograde prodegenerative signaling after injury.

    Evidence acyl-RAC palmitoylation assays, in vitro DLK phosphorylation by JNK3, isoform KO/knockdown, vesicle co-localization, and in vivo optic nerve crush

    PMID:35349303

    Open questions at the time
    • DLK phospho-site phosphorylated by JNK3 not mapped
    • Palmitoyltransferase responsible in vivo unconfirmed

Open questions

Synthesis pass · forward-looking unresolved questions
  • How JNK3's distinct subcellular pools (arrestin-cytosolic, mitochondrial, Golgi, axonal-vesicular) are coordinated to select among its many substrates and dictate apoptotic versus trafficking versus proliferative outputs remains unresolved.
  • No unified model coupling localization to substrate choice
  • Substrates linking JNK3 to mitochondrial ceramide synthase and Bim/Fas induction unidentified
  • Human disease causality (intellectual disability, Hirschsprung) rests on partial genetic evidence

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 6 GO:0016740 transferase activity 5 GO:0140110 transcription regulator activity 2
Localization
GO:0005739 mitochondrion 2 GO:0005829 cytosol 2 GO:0031410 cytoplasmic vesicle 2 GO:0005794 Golgi apparatus 1
Pathway
R-HSA-1643685 Disease 4 R-HSA-5357801 Programmed Cell Death 4 R-HSA-162582 Signal Transduction 3 R-HSA-74160 Gene expression (Transcription) 2
Partners
ARRB2DLG4KLF9MAP2K4MAP2K7MAP3K12MYD88SCG10
Complex memberships
ASK1–MKK4/7–JNK3 arrestin-3 scaffold moduleDLK–JNK3 module

Evidence

Reading pass · 39 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 JNK3 (encoded by Jnk3) is required for excitotoxic glutamate-receptor agonist (kainic acid)-induced hippocampal neuron apoptosis and seizure activity in mice; Jnk3 knockout mice show markedly reduced phosphorylation of c-Jun and AP-1 transcriptional activity following kainic acid treatment, placing JNK3 upstream of c-Jun/AP-1 in the excitotoxic apoptosis pathway. Jnk3 germline knockout mice, kainic acid excitotoxicity model, c-Jun phosphorylation and AP-1 reporter assays Nature High 9349820
1998 Crystal structure of unphosphorylated JNK3 in complex with an ATP analog reveals a typical kinase fold with a well-ordered ATP-binding site; the unphosphorylated enzyme adopts an open conformation with misaligned catalytic residues and a phosphorylation lip that partially occludes the substrate-binding site, accounting for low basal activity. X-ray crystallography (crystal structure of JNK3 with ATP analog adenylyl imidodiphosphate) Structure High 9739089
1995 p493F12 (JNK3) autophosphorylates both threonine and tyrosine residues in vitro and is exclusively expressed in the nervous system, consistent with a MAP kinase family member. Autophosphorylation in vitro assay, cDNA molecular characterization, Northern blot / immunochemistry for tissue expression Neuron Medium 7826642
2000 Beta-arrestin 2 directly binds JNK3 (identified by yeast two-hybrid and co-immunoprecipitation from mouse brain and COS-7 cells) and scaffolds the ASK1–MKK4–JNK3 signaling module; beta-arrestin 2 causes cytosolic retention of JNK3 and enhances ASK1-stimulated JNK3 phosphorylation. Angiotensin II receptor (AT1A) stimulation triggers co-localization of beta-arrestin 2 and active JNK3 to intracellular vesicles. Yeast two-hybrid screen, reciprocal co-immunoprecipitation from mouse brain and transfected COS-7 cells, confocal co-localization, JNK3 kinase phosphorylation assays Science High 11090355
2000 Full activation of JNK3α1 requires both MKK4 and MKK7: MKK7 alone monophosphorylates Thr on JNK3α1 conferring ~250-fold increase in Vmax, while MKK4 alone produces no detectable phosphorylation or activity increase; bisphosphorylation by MKK4+MKK7 confers ~715-fold increase in Vmax. Threonine monophosphorylation by MKK7 is sufficient for measurable JNK3 activity. In vitro kinase reconstitution with purified MKK4, MKK7, and JNK3α1; mass spectrometry phosphorylation mapping; steady-state kinetics (kcat, Km) Biochemistry High 10715136
2001 The RRSLHL motif in the C-terminal domain of beta-arrestin 2 is the JNK3 docking site; replacing these residues with the corresponding KP residues of beta-arrestin 1 abrogates both JNK3 binding and enhancement of JNK3 phosphorylation by MKK4. The specific step enhanced by beta-arrestin 2 scaffold activity is phosphorylation of JNK3 by MKK4. Chimeric beta-arrestin constructs, site-directed mutagenesis, co-immunoprecipitation, JNK3 phosphorylation assays in transfected cells The Journal of Biological Chemistry High 11356842
2001 JNK3 directly binds and phosphorylates SCG10 (a neuronal microtubule regulator) at Ser-62 and Ser-73 in vitro; this phosphorylation reduces SCG10's microtubule-destabilizing activity. Endogenous SCG10 undergoes increased phosphorylation in sympathetic neurons during NGF deprivation coincident with JNK3 activation. In vitro kinase assay with purified proteins, phosphorylation site mapping, microtubule destabilization assay, co-immunoprecipitation (tight/specific binding of SCG10 to JNK3), sympathetic neuron NGF deprivation model FEBS Letters High 11718727
2001 JNK3 is required for c-Jun phosphorylation and induction and subsequent apoptosis in sympathetic neurons deprived of NGF; oxidative stress following NGF deprivation is normal in JNK3-deficient neurons, placing JNK3 specifically in the c-Jun activation branch rather than upstream of ROS. Sympathetic neurons from Jnk3 knockout mice, NGF deprivation model, quantitative c-Jun phosphorylation, c-jun mRNA induction, apoptosis scoring Journal of Neurochemistry High 11461965
2002 JNK3 phosphorylates c-Jun (N-terminal phosphorylation) and ATF-2 in PC12 cells, with differential substrate choice depending on context: UV/taxol-induced cell death is associated with ATF-2 phosphorylation, while NGF-induced differentiation is associated with c-Jun phosphorylation and increased neurite outgrowth. JNK3-p54 transfection in PC12 cells (JNK3-null background), kinase substrate phosphorylation assays, neurite length/number quantification, UV and taxol treatments The Journal of Biological Chemistry Medium 12401814
2002 JNK3 (together with GSK-3β and ΔMEKKl) phosphorylates tau at multiple pathological epitopes including AT100 in COS-7 cells, and co-expression of these kinases leads to detergent-insoluble, Thioflavin-S-reactive short tau fibrils (oligomeric pretangle formation). Adenovirus-mediated co-expression of tau, ΔMEKK, JNK3, and GSK-3β in COS-7 cells; immunoblotting for tau phospho-epitopes; Thioflavin-S staining; detergent solubility fractionation The Journal of Biological Chemistry Medium 12191990
2003 Targeted deletion of Jnk3 reduces stress-induced JNK activity in the brain and protects against neuronal death after cerebral ischemia-hypoxia; downstream mechanism includes reduced induction of Bim and Fas and attenuated mitochondrial cytochrome c release. Jnk3 knockout mice, cerebral ischemia-hypoxia model, JNK activity assays, Bim/Fas expression, cytochrome c immunoblotting Proceedings of the National Academy of Sciences of the USA High 14657393
2003 Crystal structures of JNK3 in complex with three classes of ATP-competitive inhibitors reveal the atomic interactions at the active site and provide structural basis for potency and selectivity over p38 and other MAP kinases. X-ray crystallography (four crystal structures of JNK3-inhibitor complexes) Chemistry & Biology High 12954329
1997 JNK3 (as well as JNK1 and JNK2) phosphorylates mouse p53 at serine 34 in vitro and associates with p53 in vivo in 293T cells; a dominant-negative JNK1 mutant does not phosphorylate p53, confirming that kinase activity is required. In vitro kinase assay, dominant-negative mutant, co-immunoprecipitation from 293T cells Oncogene Medium 9393873
2005 JNK3 (but not JNK1 or JNK2) phosphorylates APP at Thr668 during neuronal differentiation in primary neurons, disrupting the AICD–Fe65 stabilizing interaction and downregulating AICD-mediated nuclear signaling. JNK3 thus physiologically limits APP signaling. Primary neuron cultures, JNK isoform-selective siRNA and genetic KO, APP Thr668 phosphorylation immunoblot, AICD-Fe65 co-immunoprecipitation, nuclear AICD localization assay The Journal of Neuroscience High 15944381
2006 All four arrestin subtypes (including rod, cone, arrestin-2, and arrestin-3) in their basal (inactive receptor-unbound) conformation bind JNK3 and Mdm2 and re-localize them from the nucleus to the cytoplasm in HEK293 cells. Arrestin mutants 'frozen' in the basal conformation are most efficacious, indicating that free arrestin is likely pre-loaded with JNK3 before receptor binding. GFP-JNK3 and GFP-Mdm2 nuclear exclusion assay in HEK293 cells, arrestin conformation mutants, co-expression and fluorescence microscopy The Journal of Biological Chemistry Medium 16737965
2007 After spinal cord injury, JNK3 phosphorylates Mcl-1 at Ser121 (a Pro-directed site), which displaces Pin1 from its stabilizing Thr163-Pro binding site on Mcl-1 and promotes Mcl-1 ubiquitination and degradation, thereby releasing cytochrome c and triggering oligodendrocyte apoptosis. JNK3-/- mice show reduced Mcl-1 degradation and reduced cytochrome c release, while Pin1-/- mice show the opposite. In vitro kinase assay (JNK3 phosphorylation of Mcl-1), co-immunoprecipitation (Pin1-Mcl-1), ubiquitination assay, JNK3-/- and Pin1-/- mice, cytochrome c release, oligodendrocyte apoptosis quantification The Journal of Neuroscience High 17670986
2007 MyD88-5 (a neuronal adaptor) co-immunoprecipitates with JNK3 and recruits JNK3 from the cytosol to mitochondria in vitro; MyD88-5 co-purifies with mitochondria and co-localizes with JNK3 in neurons. MyD88-5-deficient hippocampal neurons are protected from oxygen-glucose deprivation-induced death. Co-immunoprecipitation, subcellular fractionation and co-purification with mitochondria, MyD88-5/GFP BAC transgenic mice, MyD88-5 knockout neurons, oxygen-glucose deprivation model The Journal of Experimental Medicine High 17724133
2007 JNK3 signaling in cerebral ischemia/reperfusion activates mitochondrial ceramide synthase via post-translational mechanisms, leading to ceramide accumulation in mitochondria that damages the respiratory chain; JNK3-deficient mice show abolished ceramide generation and respiratory chain damage following IR. Ceramide mass measurement, ceramide synthase activity assay, mitochondrial fractionation, JNK3-/- mice, cerebral ischemia/reperfusion model The Journal of Biological Chemistry High 17609208
2009 Pathogenic huntingtin (polyQ-Htt) activates JNK3 (not JNK1) in neurons; activated JNK3 phosphorylates a specific residue in the kinesin-1 motor domain (identified by mass spectrometry), reducing kinesin-1 binding to microtubules and thereby inhibiting fast axonal transport. Squid axoplasm FAT assay, cellular and mouse HD models, JNK3 siRNA, mass spectrometry identification of kinesin-1 phosphorylation site, kinesin-1 microtubule binding assay Nature Neuroscience High 19525941
2009 SDF-1α activates JNK3 in endothelial cells via eNOS-dependent production of NO, which S-nitrosylates MKP7 and inactivates it, preventing MKP7 from dephosphorylating and inactivating JNK3; active JNK3 is critical for SDF-1α-induced endothelial cell migration. Co-immunoprecipitation, eNOS knockdown/inhibition, S-nitrosylation assay, MKP7 phosphatase activity assay, cell migration assay, JNK3 activity assay Proceedings of the National Academy of Sciences of the USA High 19307591
2011 Arrestin-3 (β-arrestin 2) residue Val-343 is the key contributor to JNK3 activation, with Leu-278, Ser-280, His-350, Asp-351, His-352, and Ile-353 playing supporting roles. Both N- and C-terminal domains of arrestin-3 are involved, with the C-terminal domain more important. The strength of binding of ASK1 or JNK3 to arrestin does not correlate with the ability to promote JNK3 phosphorylation. Arrestin-2/3 chimeras and point mutants, co-immunoprecipitation, JNK3 phosphorylation assay in cells The Journal of Biological Chemistry Medium 21715332
2011 PrPC modulates GluR6/7-PSD-95-mediated JNK3 activation; in Prnp-null mice, kainate triggers enhanced GluR6-PSD-95 interaction and JNK3 pathway activation. Double Prnp/Jnk3 knockout mice are protected from kainate neurotoxicity, placing JNK3 downstream of the PrPC-GluR6/PSD-95 signaling axis. Prnp-/- and Jnk3-/- single and double knockout mice, kainic acid model, pharmacological JNK3 inhibition, AMPA/KA receptor antagonists, co-immunoprecipitation of GluR6-PSD-95 Molecular Biology of the Cell High 21757544
2012 Aβ42 activates AMPK→mTOR inhibition→ER stress→JNK3 activation; activated JNK3 phosphorylates APP at T668, facilitating APP endocytosis and amyloidogenic processing, creating a feed-forward loop that perpetuates Aβ42 production. Deletion of JNK3 from FAD mice dramatically reduces Aβ42 levels and plaque load and improves cognition. JNK3-/- mice, FAD mouse model, pharmacological translation blockade, APP T668 phosphorylation immunoblot, Aβ42 ELISA, APP endocytosis assay, Morris water maze Neuron High 22958823
2012 JNK2 and JNK3 are the isoforms activated in injured axons of retinal ganglion cells following axonal injury; combined deficiency of Jnk2 and Jnk3 provides robust long-term protection against axonal injury-induced RGC death and prevents JUN phosphorylation, demonstrating that JNK2/JNK3-JUN signaling is the major pathway triggering RGC death. Single and combined Jnk2/Jnk3 knockout mice, optic nerve crush axonal injury model, JUN phosphorylation immunostaining, RGC survival counting, BRN3B expression Neurobiology of Disease High 22353563
2013 Arrestin-3 directly interacts with MKK7 in addition to MKK4 and JNK3α2 (using purified proteins); binding of JNK3α2 to arrestin-3 promotes arrestin-3 interaction with MKK4 while reducing its binding to MKK7. The optimal arrestin-3 concentration for scaffolding MKK7-JNK3α2 is ~10-fold higher than for MKK4-JNK3α2, revealing a concentration-dependent scaffold mechanism. In vitro binding assays with purified proteins, co-immunoprecipitation in intact cells, JNK3α2 phosphorylation assay The Journal of Biological Chemistry High 23960075
2013 Truncated JNK3 proteins associated with intellectual disability patients, although capable of weak interaction with JNK scaffolds, cannot phosphorylate c-Jun in vitro. JNK3 interacts with PSD-95, SAP102, and SHANK3 (identified as novel partners), and JNK3 phosphorylates PSD-95 in vitro, whereas disease-associated truncated JNK3 does not. JNK3 and PSD-95 co-localize at synaptic sites in hippocampal neurons. In vitro kinase assay (c-Jun and PSD-95 substrates), co-immunoprecipitation for scaffold binding, yeast two-hybrid and immunoprecipitation for new binding partners, immunofluorescence in hippocampal neurons Human Genetics High 23329067
2013 JNK3 undergoes palmitoylation in response to excitotoxic NMDA stimulation or overexpression of the palmitoyl transferase zD17, causing association with the Golgi complex independently of kinase activity. Golgi-associated JNK3 binds the phosphatase Sac1, increasing Sac1 at the Golgi and depleting PI4P, thereby inhibiting post-Golgi secretory trafficking of AMPA receptor subunit GluR1. Palmitoylation assay, JNK3 kinase-dead and palmitoylation-deficient mutants, Golgi fractionation, Sac1 co-immunoprecipitation, PI4P immunostaining, GluR1 surface trafficking assay, peptide disruption experiments in primary neurons Science Signaling High 23838184
2015 EphrinB2 signaling represses JNK3 activity via STAT1; phosphotyrosine-EphrinB2 activates STAT1, which suppresses JNK3. In the absence of JNK3, hyaloid vessel physiological pruning is impaired, demonstrating that JNK3 activation causes endothelial cell death required for vessel pruning. Jnk3 knockout mice, EphrinB2 signaling constructs, STAT1 signaling assays, hyaloid vessel imaging, retinal vascular analysis Nature Communications High 25807892
2016 A short 25-residue peptide from arrestin-3 (the JNK3-binding element) also binds MKK4, MKK7, and ASK1 and is sufficient to enhance JNK3 activity in cells. The homologous arrestin-2 peptide (differing in four positions) binds MKK4 but not MKK7 or JNK3 and cannot enhance JNK3 activation, identifying the minimal scaffold element. Binding assays with purified proteins and peptides, JNK3 phosphorylation assay in cells, comparison of arrestin-2 vs. arrestin-3 peptides Scientific Reports Medium 26868142
2017 KLF9 transcription factor suppresses axon growth through direct interaction with MAPK10/JNK3; JNK3 is required for KLF9's axon-growth-suppressive activity. Mutation of two JNK3-phosphorylation acceptor sites on KLF9 (Ser106 and Ser110), or disruption of the JNK3-binding domain of KLF9, abolishes neurite growth suppression in vitro and promotes axon regeneration in vivo. Co-immunoprecipitation (KLF9-JNK3 interaction), site-directed mutagenesis (Ser106/Ser110), shRNA knockdown, neurite outgrowth assay, optic nerve crush regeneration in rats The Journal of Neuroscience High 28871032
2018 Arrestin-3 shows >15-fold higher affinity for inactive JNK3 than for active (phosphorylated) JNK3, with a shift in binding site upon JNK3 activation. Catalytic phosphorylation of JNK3 at Thr-221 by MKK7 is ~100-fold faster than phosphorylation of Tyr-223 by MKK4 (with or without arrestin-3). Release of activated JNK3 from the scaffold is essential for signal amplification, suggesting a 'conveyor belt' mechanism. Binding affinity measurements (phosphorylated vs. unphosphorylated JNK3), systems biochemistry modeling with Bayesian inference, in vitro phosphorylation kinetics Proceedings of the National Academy of Sciences of the USA High 30591558
2019 The β1 strand of arrestin-3 is the major interaction site with JNK3; C-lobe regions near the activation loop of JNK3 form the JNK3 interface with arrestin-3, and this interface is variable depending on ATP-binding status. C-terminal truncation of arrestin-3 (pre-activation) facilitates the arrestin-3/JNK3 interaction by exposing the buried β1 strand. Hydrogen/deuterium exchange mass spectrometry, 19F-NMR, tryptophan-induced Atto 655 fluorescence quenching, C-terminal truncation mutants Structure High 31080119
2022 DLK (MAP3K) and JNK3 are coupled by palmitoylation: JNK3 catalyzes positive feedback phosphorylation of DLK that further activates DLK, locking the DLK-JNK3 module in a highly active state. Both DLK and JNK3 are endogenously palmitoylated, which targets them to the same axonal vesicles. JNK3 palmitoylation is essential for axonal retrograde prodegenerative signaling after optic nerve crush in vivo; JNK2 and JNK3 (but not JNK1) promote prodegenerative axon-to-soma signaling. Palmitoylation assays (acyl-RAC), in vitro DLK phosphorylation by JNK3, optic nerve crush in vivo, JNK isoform knockdown/KO, axonal retrograde signaling assays, vesicle co-localization Science Signaling High 35349303
2020 DLK (Map3k12) associates with and activates JNK3 in pancreatic beta cells; Dlk overexpression increases JNK3 activity, and this DLK-JNK3 cascade stimulates expression of cyclins Ccnd1 and Ccnd2, which are required for postnatal beta-cell replication. Silencing of Dlk or Jnk3 in neonatal islet cells markedly reduces beta-cell replication and cyclin expression. Co-immunoprecipitation (DLK-JNK3 interaction), JNK3 kinase activity assay, Dlk/Jnk3 siRNA knockdown in neonatal islet cells, cyclin expression by RT-PCR/immunoblot, beta-cell replication quantification Cellular and Molecular Life Sciences High 32189007
2009 JNK3 is protected from dephosphorylation/inactivation by MKP7 when MKP7 is associated with the beta-arrestin 2 scaffold; angiotensin II receptor stimulation causes rapid (within 5 min) dissociation of MKP7 from beta-arrestin 2, permitting JNK3 activation, followed by reassociation of MKP7 with beta-arrestin 2 on endocytic vesicles at 30-60 min. Co-immunoprecipitation (MKP7–beta-arrestin 2 interaction), JNK3 dephosphorylation assay, AT1aR stimulation time course, endosome localization assay The Journal of Biological Chemistry Medium 15888437
2012 In insulin-secreting cells, JNK3 (but not JNK1 or JNK2) knockdown decreases IRS2 protein expression and blocks Akt2 (but not Akt1) activation by insulin, via reduced FoxO3A activity (FoxO3A controls IRS2 expression). JNK3 silencing in these cells increases c-Jun levels. JNK3 thus maintains IRS2–Akt2 pro-survival signaling in beta cells. JNK3/JNK1/JNK2 isoform-specific siRNA in INS-1E cells, IRS2/Akt2 immunoblotting, FoxO3A activity assay, c-Jun quantification PloS One Medium 22563476
2008 Combined deficiency of Jnk2 and Jnk3 (but not either alone) completely abrogates apoptosis of dopamine neurons in the substantia nigra in a 6-hydroxydopamine model, with full protection of the cell soma but no protection of axons, demonstrating that JNK2/JNK3 together specifically mediate apoptotic somal death via distinct mechanisms from axon degeneration. Single and double Jnk2/Jnk3 knockout mice, intrastriatal 6-OHDA model, dopamine neuron counting, axon degeneration assessment Journal of Neurochemistry High 19014392
2016 A novel zebrafish mapk10 (ortholog of MAPK10/JNK3) loss-of-function mutation reduces enteric neuron numbers, and introduction of mapk10 mutations into ret heterozygous zebrafish enhances the enteric nervous system deficit, supporting MAPK10 as a Hirschsprung disease susceptibility/modifier locus. Zebrafish mapk10 loss-of-function mutants, genetic epistasis with ret heterozygotes, live imaging of ENS progenitor migration, neuron counting PLoS Genetics Medium 27902697
2017 AICD (APP intracellular domain) interacts with the JNK3 gene locus and upregulates JNK3 expression after optic nerve axotomy (demonstrated by ChIP and luciferase reporter assay); JNK3 upregulation contributes to retinal ganglion cell death. APP knockout reduces ONA-induced JNK3 and pJNK expression, and gamma-secretase inhibitors similarly reduce JNK3 expression and protect RGCs. Microarray/pathway analysis, chromatin immunoprecipitation (AICD at JNK3 locus), luciferase reporter assay, APP KO mice, gamma-secretase inhibitor treatment, JNK3 immunoblot, RGC survival counting Cell Death and Differentiation High 29238071

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1997 Absence of excitotoxicity-induced apoptosis in the hippocampus of mice lacking the Jnk3 gene. Nature 1064 9349820
2000 Beta-arrestin 2: a receptor-regulated MAPK scaffold for the activation of JNK3. Science (New York, N.Y.) 692 11090355
2003 A critical role of neural-specific JNK3 for ischemic apoptosis. Proceedings of the National Academy of Sciences of the United States of America 362 14657393
2012 JNK3 perpetuates metabolic stress induced by Aβ peptides. Neuron 200 22958823
2009 Pathogenic huntingtin inhibits fast axonal transport by activating JNK3 and phosphorylating kinesin. Nature neuroscience 197 19525941
2007 MyD88-5 links mitochondria, microtubules, and JNK3 in neurons and regulates neuronal survival. The Journal of experimental medicine 191 17724133
1998 Crystal structure of JNK3: a kinase implicated in neuronal apoptosis. Structure (London, England : 1993) 185 9739089
1995 p493F12 kinase: a novel MAP kinase expressed in a subset of neurons in the human nervous system. Neuron 183 7826642
2007 JNK3 signaling pathway activates ceramide synthase leading to mitochondrial dysfunction. The Journal of biological chemistry 135 17609208
2012 JNK2 and JNK3 are major regulators of axonal injury-induced retinal ganglion cell death. Neurobiology of disease 124 22353563
2006 Visual and both non-visual arrestins in their "inactive" conformation bind JNK3 and Mdm2 and relocalize them from the nucleus to the cytoplasm. The Journal of biological chemistry 118 16737965
2001 Identification of a motif in the carboxyl terminus of beta -arrestin2 responsible for activation of JNK3. The Journal of biological chemistry 118 11356842
1996 Developmental expression in the mouse nervous system of the p493F12 SAP kinase. Brain research. Molecular brain research 116 8717339
2003 The structure of JNK3 in complex with small molecule inhibitors: structural basis for potency and selectivity. Chemistry & biology 113 12954329
2002 Aberrant tau phosphorylation by glycogen synthase kinase-3beta and JNK3 induces oligomeric tau fibrils in COS-7 cells. The Journal of biological chemistry 113 12191990
1997 JNK1, JNK2 and JNK3 are p53 N-terminal serine 34 kinases. Oncogene 112 9393873
2004 Targeting JNK3 for the treatment of neurodegenerative disorders. Drug discovery today 109 15501728
2005 Physiological regulation of the beta-amyloid precursor protein signaling domain by c-Jun N-terminal kinase JNK3 during neuronal differentiation. The Journal of neuroscience : the official journal of the Society for Neuroscience 98 15944381
2017 KLF9 and JNK3 Interact to Suppress Axon Regeneration in the Adult CNS. The Journal of neuroscience : the official journal of the Society for Neuroscience 85 28871032
2016 Metformin protects the brain against ischemia/reperfusion injury through PI3K/Akt1/JNK3 signaling pathways in rats. Physiology & behavior 80 28017679
2015 Increased levels of cerebrospinal fluid JNK3 associated with amyloid pathology: links to cognitive decline. Journal of psychiatry & neuroscience : JPN 78 25455349
2011 JNK3 as a therapeutic target for neurodegenerative diseases. Journal of Alzheimer's disease : JAD 70 21321401
2001 JNK3 contributes to c-Jun activation and apoptosis but not oxidative stress in nerve growth factor-deprived sympathetic neurons. Journal of neurochemistry 70 11461965
2009 SDF-1alpha stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration. Proceedings of the National Academy of Sciences of the United States of America 68 19307591
2002 A single c-Jun N-terminal kinase isoform (JNK3-p54) is an effector in both neuronal differentiation and cell death. The Journal of biological chemistry 66 12401814
2000 Activation of JNK3 alpha 1 requires both MKK4 and MKK7: kinetic characterization of in vitro phosphorylated JNK3 alpha 1. Biochemistry 66 10715136
2008 JNK2 and JNK3 combined are essential for apoptosis in dopamine neurons of the substantia nigra, but are not required for axon degeneration. Journal of neurochemistry 65 19014392
2016 Quercetin ameliorates ischemia/reperfusion-induced cognitive deficits by inhibiting ASK1/JNK3/caspase-3 by enhancing the Akt signaling pathway. Biochemical and biophysical research communications 63 27450812
2021 A Highly Selective In Vitro JNK3 Inhibitor, FMU200, Restores Mitochondrial Membrane Potential and Reduces Oxidative Stress and Apoptosis in SH-SY5Y Cells. International journal of molecular sciences 62 33918172
2010 JNK3 mediates paraquat- and rotenone-induced dopaminergic neuron death. Journal of neuropathology and experimental neurology 61 20418776
2015 Genetic inhibition of JNK3 ameliorates spinal muscular atrophy. Human molecular genetics 60 26423457
2020 JNK3 as Therapeutic Target and Biomarker in Neurodegenerative and Neurodevelopmental Brain Diseases. Cells 58 32998477
2011 Identification of arrestin-3-specific residues necessary for JNK3 kinase activation. The Journal of biological chemistry 57 21715332
2011 Neuroprotective role of PrPC against kainate-induced epileptic seizures and cell death depends on the modulation of JNK3 activation by GluR6/7-PSD-95 binding. Molecular biology of the cell 57 21757544
2007 Opposite regulation of oligodendrocyte apoptosis by JNK3 and Pin1 after spinal cord injury. The Journal of neuroscience : the official journal of the Society for Neuroscience 55 17670986
2009 Structure-activity relationships and X-ray structures describing the selectivity of aminopyrazole inhibitors for c-Jun N-terminal kinase 3 (JNK3) over p38. The Journal of biological chemistry 54 19261605
2003 Antioxidant NAC and AMPA/KA receptor antagonist DNQX inhibited JNK3 activation following global ischemia in rat hippocampus. Neuroscience research 54 12767482
2015 EphrinB2 controls vessel pruning through STAT1-JNK3 signalling. Nature communications 53 25807892
2005 The neuroprotective effects of K252a through inhibiting MLK3/MKK7/JNK3 signaling pathway on ischemic brain injury in rat hippocampal CA1 region. Neuroscience 53 15680699
2016 Peptide mini-scaffold facilitates JNK3 activation in cells. Scientific reports 52 26868142
2015 Neuroprotection of Sevoflurane Against Ischemia/Reperfusion-Induced Brain Injury Through Inhibiting JNK3/Caspase-3 by Enhancing Akt Signaling Pathway. Molecular neurobiology 52 25687432
2005 Dynamic interaction between the dual specificity phosphatase MKP7 and the JNK3 scaffold protein beta-arrestin 2. The Journal of biological chemistry 52 15888437
2019 Cervical Cancer Cells-Secreted Exosomal microRNA-221-3p Promotes Invasion, Migration and Angiogenesis of Microvascular Endothelial Cells in Cervical Cancer by Down-Regulating MAPK10 Expression. Cancer management and research 51 31849520
2020 19q13 KRAB zinc-finger protein ZNF471 activates MAPK10/JNK3 signaling but is frequently silenced by promoter CpG methylation in esophageal cancer. Theranostics 49 32089740
2017 Dysregulated miR-27a-3p promotes nasopharyngeal carcinoma cell proliferation and migration by targeting Mapk10. Oncology reports 49 28393229
2012 The neuroprotective effect of losartan through inhibiting AT1/ASK1/MKK4/JNK3 pathway following cerebral I/R in rat hippocampal CA1 region. CNS neuroscience & therapeutics 49 23095236
2009 Blockade of the translocation and activation of c-Jun N-terminal kinase 3 (JNK3) attenuates dopaminergic neuronal damage in mouse model of Parkinson's disease. Neurochemistry international 49 19428783
2014 Design and synthesis of highly potent and isoform selective JNK3 inhibitors: SAR studies on aminopyrazole derivatives. Journal of medicinal chemistry 48 25393557
2007 Cone arrestin binding to JNK3 and Mdm2: conformational preference and localization of interaction sites. Journal of neurochemistry 48 17680991
2001 The c-Jun NH2-terminal kinase3 (JNK3) gene: genomic structure, chromosomal assignment, and loss of expression in brain tumors. Journal of human genetics 48 11322657
2013 JNK3 enzyme binding to arrestin-3 differentially affects the recruitment of upstream mitogen-activated protein (MAP) kinase kinases. The Journal of biological chemistry 45 23960075
2012 17β-Estradiol inhibits apoptotic cell death of oligodendrocytes by inhibiting RhoA-JNK3 activation after spinal cord injury. Endocrinology 45 22700771
2014 H₂S attenuates cognitive deficits through Akt1/JNK3 signaling pathway in ischemic stroke. Behavioural brain research 44 24768640
2006 Akt inhibits MLK3/JNK3 signaling by inactivating Rac1: a protective mechanism against ischemic brain injury. Journal of neurochemistry 44 16831194
2022 Aptamer engineering exosomes loaded on biomimetic periosteum to promote angiogenesis and bone regeneration by targeting injured nerves via JNK3 MAPK pathway. Materials today. Bio 43 36186848
2009 JNK3 is abundant in insulin-secreting cells and protects against cytokine-induced apoptosis. Diabetologia 43 19609503
2013 Astragalus injection protects cerebral ischemic injury by inhibiting neuronal apoptosis and the expression of JNK3 after cerebral ischemia reperfusion in rats. Behavioral and brain functions : BBF 42 24083559
2013 Characterisation of de novo MAPK10/JNK3 truncation mutations associated with cognitive disorders in two unrelated patients. Human genetics 41 23329067
2019 Multistage Screening Reveals 3-Substituted Indolin-2-one Derivatives as Novel and Isoform-Selective c-Jun N-terminal Kinase 3 (JNK3) Inhibitors: Implications to Drug Discovery for Potential Treatment of Neurodegenerative Diseases. Journal of medicinal chemistry 40 31268308
2016 A Novel Zebrafish ret Heterozygous Model of Hirschsprung Disease Identifies a Functional Role for mapk10 as a Modifier of Enteric Nervous System Phenotype Severity. PLoS genetics 39 27902697
2016 Neuroprotection of Cilostazol against ischemia/reperfusion-induced cognitive deficits through inhibiting JNK3/caspase-3 by enhancing Akt1. Brain research 38 27769787
2018 Arrestin-3 scaffolding of the JNK3 cascade suggests a mechanism for signal amplification. Proceedings of the National Academy of Sciences of the United States of America 37 30591558
2020 Biological Properties of JNK3 and Its Function in Neurons, Astrocytes, Pancreatic β-Cells and Cardiovascular Cells. Cells 36 32751228
2020 Photobiomodulation suppresses JNK3 by activation of ERK/MKP7 to attenuate AMPA receptor endocytosis in Alzheimer's disease. Aging cell 35 33336891
2007 K252a prevents nigral dopaminergic cell death induced by 6-hydroxydopamine through inhibition of both mixed-lineage kinase 3/c-Jun NH2-terminal kinase 3 (JNK3) and apoptosis-inducing kinase 1/JNK3 signaling pathways. Molecular pharmacology 35 17855652
2021 miR-335-5p suppresses gastric cancer progression by targeting MAPK10. Cancer cell international 34 33482821
2009 Preconditioning neuroprotection in global cerebral ischemia involves NMDA receptor-mediated ERK-JNK3 crosstalk. Neuroscience research 34 19373993
2017 CoQ10 Augments Rosuvastatin Neuroprotective Effect in a Model of Global Ischemia via Inhibition of NF-κB/JNK3/Bax and Activation of Akt/FOXO3A/Bim Cues. Frontiers in pharmacology 33 29081748
2002 JNK3 contributes to c-jun induction and apoptosis in 4-hydroxynonenal-treated sympathetic neurons. Journal of neuroscience research 32 12424734
2016 Rosmarinic acid protects rat hippocampal neurons from cerebral ischemia/reperfusion injury via the Akt/JNK3/caspase-3 signaling pathway. Brain research 31 27923634
2005 Truncation of the CNS-expressed JNK3 in a patient with a severe developmental epileptic encephalopathy. Human genetics 31 16249883
2017 APP upregulation contributes to retinal ganglion cell degeneration via JNK3. Cell death and differentiation 30 29238071
2017 Neuroprotective Effects of the Absence of JNK1 or JNK3 Isoforms on Kainic Acid-Induced Temporal Lobe Epilepsy-Like Symptoms. Molecular neurobiology 29 28664455
2001 c-Jun N-terminal kinase-3 (JNK3)/stress-activated protein kinase-beta (SAPKbeta) binds and phosphorylates the neuronal microtubule regulator SCG10. FEBS letters 29 11718727
2018 New insights into the structural dynamics of the kinase JNK3. Scientific reports 28 29930333
2010 Differences in activation of ERK1/2 and p38 kinase in Jnk3 null mice following KA treatment. Journal of neurochemistry 28 20534003
2012 JNK3 maintains expression of the insulin receptor substrate 2 (IRS2) in insulin-secreting cells: functional consequences for insulin signaling. PloS one 27 22563476
2010 JNK1, JNK2, and JNK3 are involved in P-glycoprotein-mediated multidrug resistance of hepatocellular carcinoma cells. Hepatobiliary & pancreatic diseases international : HBPD INT 27 20525557
2009 1-Aryl-3,4-dihydroisoquinoline inhibitors of JNK3. Bioorganic & medicinal chemistry letters 27 19303774
2014 Protection of Momordica charantia polysaccharide against intracerebral hemorrhage-induced brain injury through JNK3 signaling pathway. Journal of receptor and signal transduction research 26 25264226
2024 Berberine modulates ovarian cancer autophagy and glycolysis through the LINC01123/P65/MAPK10 signaling axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 25 39395322
2008 Co-activation of GABA receptors inhibits the JNK3 apoptotic pathway via the disassembly of the GluR6-PSD95-MLK3 signaling module in cerebral ischemic-reperfusion. FEBS letters 25 18307989
2006 Down-regulation Cdc42 attenuates neuronal apoptosis through inhibiting MLK3/JNK3 cascade during ischemic reperfusion in rat hippocampus. Cellular signalling 25 17161586
2014 Inhibition of JNK3 promotes apoptosis induced by BH3 mimetic S1 in chemoresistant human ovarian cancer cells. Anatomical record (Hoboken, N.J. : 2007) 24 25044439
2004 Postsynaptic density protein 95 antisense oligodeoxynucleotides inhibits the activation of MLK3 and JNK3 via the GluR6.PSD-95.MLK3 signaling module after transient cerebral ischemia in rat hippocampus. Neuroscience letters 24 15308300
2020 miR-137-3p Modulates the Progression of Prostate Cancer by Regulating the JNK3/EZH2 Axis. OncoTargets and therapy 23 32884286
2020 Repurposing FDA Approved Drugs as JNK3 Inhibitor for Prevention of Neuroinflammation Induced by MCAO in Rats. Journal of inflammation research 23 33384558
2010 Neuroprotection of ethanol against ischemia/reperfusion-induced brain injury through decreasing c-Jun N-terminal kinase 3 (JNK3) activation by enhancing GABA release. Neuroscience 23 20219637
2022 Palmitoylation couples the kinases DLK and JNK3 to facilitate prodegenerative axon-to-soma signaling. Science signaling 22 35349303
2022 Discovery of novel imidazole chemotypes as isoform-selective JNK3 inhibitors for the treatment of Alzheimer's disease. European journal of medicinal chemistry 22 36343411
2013 JNK3 couples the neuronal stress response to inhibition of secretory trafficking. Science signaling 22 23838184
2006 Three-dimensional quantitative structure-activity relationship (3 D-QSAR) and docking studies on (benzothiazole-2-yl) acetonitrile derivatives as c-Jun N-terminal kinase-3 (JNK3) inhibitors. Bioorganic & medicinal chemistry letters 22 16989998
2015 Small peptide inhibitor of JNK3 protects dopaminergic neurons from MPTP induced injury via inhibiting the ASK1-JNK3 signaling pathway. PloS one 21 25856433
2006 Antioxidant N-acetylcysteine inhibits the activation of JNK3 mediated by the GluR6-PSD95-MLK3 signaling module during cerebral ischemia in rat hippocampus. Neuroscience letters 21 17030433
2020 Propofol suppresses the progression of non‑small cell lung cancer via downregulation of the miR‑21‑5p/MAPK10 axis. Oncology reports 20 32468043
2020 Thiophene-Pyrazolourea Derivatives as Potent, Orally Bioavailable, and Isoform-Selective JNK3 Inhibitors. ACS medicinal chemistry letters 20 33488960
2014 JNK3 is required for the cytoprotective effect of exendin 4. Journal of diabetes research 20 25025079
2022 Recent advances of small molecule JNK3 inhibitors for Alzheimer's disease. Bioorganic chemistry 19 35964505
2020 The Map3k12 (Dlk)/JNK3 signaling pathway is required for pancreatic beta-cell proliferation during postnatal development. Cellular and molecular life sciences : CMLS 19 32189007
2019 Structural Mechanism of the Arrestin-3/JNK3 Interaction. Structure (London, England : 1993) 19 31080119

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