Affinage

Showing MAPK9 — JNK2 is a alias.

MAPK9

Mitogen-activated protein kinase 9 · UniProt P45984

Length
424 aa
Mass
48.1 kDa
Annotated
2026-06-10
100 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAPK9/JNK2 is a stress-activated serine/threonine protein kinase that couples extracellular and intracellular stress signals to phosphorylation of substrates governing transcription, apoptosis, cell-cycle progression, and metabolism (PMID:8001819, PMID:15350216). It acts as the terminal kinase of a defined MAPKKK→MKK4(SEK1)/MKK7→JNK cascade, in which upstream MAPKKKs such as MLK-3 and MEKK1 (engaged via GCK and TRAF2 downstream of TNF-R1) feed into SEK1/MKK7, with MKK7 being a JNK-specific activator that predominates in TNFα- and osmotic-stress signaling (PMID:7997269, PMID:9003778, PMID:9384583, PMID:9712898, PMID:8985011). JNK2 was originally distinguished from JNK1 by a beta-strand docking region near its catalytic pocket that binds c-Jun ~25-fold more efficiently, lowering its Km for this substrate (PMID:8001819); isoform-specific scaffolds then route JNK2 to discrete biological programs, including CARMA1/Bcl10-assembled JNK2–MKK7–TAK1 complexes in TCR signaling and a MAVS–MKK7–JNK2 mitochondrial axis driving antiviral apoptosis (PMID:17189706, PMID:24651600). A central theme is JNK2's isoform-distinct and often opposing relationship to JNK1: in unstimulated cells JNK2 preferentially binds c-Jun and promotes its degradation, acting as a negative regulator of c-Jun stability and proliferation, with the apparent opposition to JNK1 reflecting competition between the isoforms (PMID:15350216, PMID:16973441). JNK2 directly phosphorylates a broad substrate set—Bcl-x(L) at Thr-47/Thr-115 to attenuate its anti-apoptotic activity, cdc25c at Ser168 to regulate the G2/M transition, GRASP65/GORASP1 at Ser277 to drive G2-specific Golgi stack separation, SIRT1 at Ser27 to control its stability, and SERCA2 to enhance its ATPase activity (PMID:10617621, PMID:12742231, PMID:25948586, PMID:18838864, PMID:33334123). Through these activities JNK2 controls developmental apoptosis, T-cell activation and Th1/Th2 balance, macrophage foam-cell formation via scavenger-receptor A phosphorylation, and atrial arrhythmogenesis via a JNK2–CaMKII–RyR2 pathway in which JNK2 also transcriptionally upregulates CaMKIIδ through c-Jun (PMID:10230788, PMID:10021384, PMID:15867147, PMID:15567863, PMID:29352041, PMID:29360953).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1994 High

    Established JNK2 as a distinct c-Jun kinase and defined the structural basis for its substrate selectivity, explaining why JNK2 is a more efficient c-Jun kinase than JNK1.

    Evidence Molecular cloning, in vitro kinase assays with Km determination, and mutagenesis mapping of the docking region

    PMID:8001819

    Open questions at the time
    • Cellular consequences of differential c-Jun binding not addressed
    • Other physiological substrates not yet known
  2. 1994 High

    Placed JNK2 in a dedicated stress-activated cascade by identifying SEK1 as a direct upstream activating kinase distinct from the ERK pathway.

    Evidence In vitro kinase assay plus dominant-negative epistasis in cells

    PMID:7997269

    Open questions at the time
    • Upstream MAPKKKs not yet defined
    • Did not distinguish JNK1 vs JNK2 specificity of SEK1
  3. 1996 High

    Extended the cascade upstream and connected it to physiology by identifying MLK-3 as a MAPKKK acting through SEK1 and by linking ceramide-initiated apoptosis to the SAPK/JNK pathway.

    Evidence In vitro phosphorylation of SEK1 by MLK-3, co-precipitation, and ceramide-treatment apoptosis assays with pathway inhibition

    PMID:8598911 PMID:9003778

    Open questions at the time
    • JNK1/JNK2 isoform specificity of these inputs unresolved
    • Direct ceramide-to-kinase linkage not biochemically defined
  4. 1997 High

    Resolved the proximal architecture downstream of TNF-R1 and defined MKK7 as a JNK-selective MAPKK, separating the survival/JNK arm from the apoptotic FADD arm.

    Evidence Dominant-negative TRAF2/FADD epistasis and in vitro kinase specificity profiling of MKK7 vs SEK1/MKK4

    PMID:8985011 PMID:9384583

    Open questions at the time
    • Whether MKK7 selectively activates JNK2 over JNK1 not addressed here
    • Scaffolding determinants of branch choice unknown
  5. 1998 Medium

    Identified GCK as the adaptor coupling TRAF2 to MEKK1 and thereby to JNK, revealing parallel JNK and p38 branches downstream of TRAF2.

    Evidence In vivo co-immunoprecipitation, in vitro kinase assays, and overexpression epistasis

    PMID:9712898

    Open questions at the time
    • Single-lab data
    • Isoform specificity for JNK2 not tested
  6. 1999 High

    Defined the in vivo developmental and immunological roles of JNK2, showing it is required with JNK1 for region-specific brain apoptosis and independently for T-cell activation and stimulus-specific thymocyte apoptosis.

    Evidence Single and compound Jnk1/Jnk2 knockout mice with histology, TUNEL/caspase assays, T-cell proliferation and cytokine assays

    PMID:10021384 PMID:10230788 PMID:10559486

    Open questions at the time
    • Molecular substrates underlying developmental phenotype not identified
    • Redundancy vs unique JNK2 functions not fully separated
  7. 2000 High

    Connected JNK activation to the mitochondrial apoptotic machinery by showing JNK phosphorylates Bcl-x(L) to disable its anti-apoptotic function after ionizing radiation.

    Evidence Translocation assay, co-IP, in vitro/in vivo kinase assay, and phospho-site mutagenesis with apoptosis rescue

    PMID:10617621

    Open questions at the time
    • JNK1 vs JNK2 contribution not separated
    • Stoichiometry of phosphorylation in vivo unclear
  8. 2001 High

    Identified MKP-7 as a cytoplasmic dual-specificity phosphatase that binds and inactivates JNK and p38, defining a negative regulator of the pathway.

    Evidence In vitro phosphatase assays, binding/co-IP, and subcellular localization

    PMID:11359773

    Open questions at the time
    • Selectivity for JNK2 vs JNK1 not addressed
    • In vivo relevance not established
  9. 2002 Medium

    Defined a DNA-damage-induced JNK activation route through PKCdelta that is MKK7-dependent and SEK1-independent, showing branch-selective upstream wiring.

    Evidence Pharmacological inhibition, kinase-dead and siRNA approaches, and co-expression epistasis

    PMID:12377781

    Open questions at the time
    • Single-lab data
    • JNK2 isoform specificity not directly demonstrated
  10. 2003 High

    Established a direct cell-cycle role by showing JNK phosphorylates cdc25c at Ser168 to inhibit its phosphatase activity and the G2/M transition.

    Evidence In vitro kinase assay, S168A mutagenesis with cdc2/cyclin B activity rescue, and phospho-specific antibody

    PMID:12742231

    Open questions at the time
    • JNK2 vs JNK1 contribution not separated here
    • Physiological context of this regulation not defined
  11. 2004 High

    Revealed the isoform-distinct logic of JNK2: it preferentially binds and degrades c-Jun in resting cells to restrain proliferation, opposite to JNK1, and linked this to atherosclerosis and mitotic fidelity.

    Evidence Reciprocal Jnk1/Jnk2 knockout fibroblasts with re-expression rescue and co-IP; macrophage-specific conditional knockouts with SR-A phosphorylation assays; dominant-negative/RNAi mitotic analysis

    PMID:15262983 PMID:15350216 PMID:15567863

    Open questions at the time
    • Whether opposing roles are intrinsic or competitive unresolved at this stage
    • Direct kinase target in mitotic anaphase defect unidentified
  12. 2005 High

    Refined the immunological role of JNK2 in autoimmunity by showing it controls Th1/Th2 cytokine balance and diabetes progression, and mapped a JIP-scaffolded negative-feedback activation loop.

    Evidence Jnk2 knockout NOD mice with insulitis/cytokine readouts; co-IP and in vitro kinase assays mapping the ASK1/JIP3/SEK1/JNK2/JIP1/Akt1 circuit

    PMID:15867147 PMID:15911620

    Open questions at the time
    • Feedback-loop findings single-lab
    • Quantitative contribution of feedback to net JNK2 output unknown
  13. 2006 High

    Reconciled the apparent JNK1/JNK2 opposition by showing through chemical genetics that both isoforms positively regulate c-Jun and proliferation, with knockout phenotypes arising from inter-isoform competition; CARMA1/Bcl10 were defined as JNK2-selective TCR scaffolds.

    Evidence Analog-sensitive kinase chemical genetics in knockout fibroblasts; CARMA1/Bcl10 knockout mice with reciprocal co-IP and isoform-selective JNK assays

    PMID:16973441 PMID:17189706

    Open questions at the time
    • How competition is resolved at the substrate level not fully mechanistic
    • Generality across cell types not established
  14. 2007 Medium

    Extended JNK2's apoptotic reach to p53 by defining a sequential JNK1→JNK2→p53 phosphorylation cascade at Ser6.

    Evidence Isoform-specific siRNA, pharmacological inhibition, p53 pulldown, and phospho-site analysis

    PMID:17525747

    Open questions at the time
    • Single-lab data
    • Direct vs indirect Ser6 phosphorylation in vivo not fully resolved
  15. 2009 Medium

    Established JNK2 as a context-dependent regulator of protein stability and metabolism, controlling SIRT1 stability via Ser27, suppressing a JNK1/c-Jun/Bcl-3 apoptotic network, promoting ABCG1 degradation and cholesterol efflux, blocking the hepatocyte mitochondrial death pathway, and downregulating beta-catenin via GSK3beta.

    Evidence Isoform-specific RNAi/knockout, half-life and phospho-site analyses, ChIP, in vivo knockdown with Bcl-2 family epistasis, and multiple interaction assays (co-IP, two-hybrid, confocal)

    PMID:18838864 PMID:19053047 PMID:19675674 PMID:19713213 PMID:19806201

    Open questions at the time
    • Each mechanism rests on single-lab evidence
    • Direct kinase–substrate phosphorylation not demonstrated for all targets
  16. 2011 Medium

    Defined a pro-migratory role for JNK2 in cancer through EPS8-complex regulation and EGFR trafficking, and produced JNK2-selective peptide inhibitors validating the migration phenotype.

    Evidence Jnk2 knockout mammary tumor cells with EPS8 knockdown rescue and co-IP; in vitro kinase IC50 profiling and knockout/rescue migration assays

    PMID:21357683 PMID:21438496

    Open questions at the time
    • Single-lab mechanistic data
    • Direct JNK2 substrate in the EPS8 axis not identified
  17. 2012 Medium

    Broadened JNK2's stress repertoire to ER stress, autophagy, neuronal injury, and therapy resistance, showing pro-survival UPR regulation, JIP-4-mediated activation that blunts cetuximab radiosensitization, and a requirement for JNK2/JNK3 in axonal injury-induced RGC death.

    Evidence siRNA/pharmacological inhibition with UPR and autophagy markers; IP-MS identification of JIP-4 with knockdown validation; isoform-specific knockout mice in optic nerve crush

    PMID:22353563 PMID:23074283 PMID:23171849

    Open questions at the time
    • UPR and JIP-4 findings single-lab
    • Direct phosphorylation targets in these contexts not defined
  18. 2014 High

    Defined a mitochondrial MAVS–MKK7–JNK2 axis as a JNK2-selective antiviral apoptotic pathway and established JNK2-specific control of pro-survival autophagy in hepatocytes.

    Evidence Jnk1/Jnk2/Mkk7 knockout cells and mice, MAVS domain-mapping co-IP, viral apoptosis assays; isoform-specific siRNA with autophagy/apoptosis readouts

    PMID:24608675 PMID:24651600

    Open questions at the time
    • Direct JNK2 substrate executing antiviral apoptosis not identified
    • Autophagy mechanism single-lab
  19. 2015 High

    Established JNK2's direct role in Golgi biogenesis and mitotic entry by identifying GRASP65 Ser277 phosphorylation as required for G2 Golgi stack separation, and provided structural basis for JNK2/3 isoform-selective inhibition.

    Evidence RNAi and three independent JNK inhibitors, GRASP65 site mutagenesis, brefeldin A epistasis, and FRAP; X-ray crystallography with L144 mutagenesis and neuronal protection assays

    PMID:25623238 PMID:25948586

    Open questions at the time
    • JNK2 vs JNK3 contribution in cellular Golgi context not fully separated
    • Structural details of JNK2-substrate docking not resolved
  20. 2016 Medium

    Linked JNK2 to hypoxic chemotherapy response by showing it activates PHD1 to drive HIF-1alpha hydroxylation and degradation in docetaxel-treated cancer cells.

    Evidence siRNA epistasis between JNK2 and PHD1, proteasome rescue, HIF-1 reporter assay, and xenograft model

    PMID:27263528

    Open questions at the time
    • Single-lab data
    • Direct vs indirect PHD1 activation not biochemically resolved
  21. 2020 High

    Defined a JNK2-driven cardiac arrhythmogenic program in the aged atrium, integrating JNK2–CaMKII–RyR2-mediated SR Ca2+ leak, c-Jun-dependent transcriptional upregulation of CaMKIIδ, and direct CaMKII-independent enhancement of SERCA2 ATPase activity.

    Evidence Transgenic JNK2-ablation mice, electrophysiology and Ca2+ imaging, ChIP and CaMKIIδ promoter assays, co-IP/phosphorylation and ATPase activity assays, and human donor heart studies

    PMID:29352041 PMID:29360953 PMID:33334123

    Open questions at the time
    • SERCA2 phosphorylation site not mapped
    • Mechanism of CaMKII activation by JNK2 not fully defined

Open questions

Synthesis pass · forward-looking unresolved questions
  • How JNK2's many isoform-selective substrate choices are coordinated by upstream scaffolds in vivo, and the structural determinants directing JNK2 to specific substrates beyond c-Jun, remain to be defined.
  • No unified structural model of JNK2 substrate docking across targets
  • Scaffold-to-substrate routing rules not generalized
  • Phosphorylation sites unmapped for several reported substrates

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 5 GO:0016740 transferase activity 4 GO:0140110 transcription regulator activity 2
Localization
GO:0005739 mitochondrion 2 GO:0005794 Golgi apparatus 1 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 4 R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-9612973 Autophagy 2
Partners
BCL10BCL2L1GORASP1JUNMAP2K4MAP2K7MAVSSIRT1
Complex memberships
CARMA1/Bcl10/MKK7/TAK1 JNK2-activating complexMAVS-MKK7-JNK2 mitochondrial signaling axis

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 JNK2 (55 kD form of JNK) was molecularly cloned and shown to phosphorylate c-Jun at its amino-terminal activation sites. JNK2 binds c-Jun approximately 25 times more efficiently than JNK1, resulting in a lower Km toward c-Jun. A small beta-strand-like region near the catalytic pocket of JNK2 was identified as the structural basis for this differential substrate recognition, serving as a docking site that increases the effective concentration of c-Jun near JNK2. Molecular cloning, in vitro kinase assays, Km determination, structural modeling and mutagenesis to map the specificity-determining region Genes & development High 8001819
1994 SEK1 (SAPK/ERK kinase-1) was identified as a direct upstream activator of SAPKs/JNKs in vitro and in vivo. SEK1 is structurally related to MAP kinase kinases (MEKs). A kinase-inactive SEK1 mutant blocks SAPK activation by extracellular stimuli without interfering with the MAPK/ERK pathway, placing SEK1 immediately upstream of SAPK/JNK in a distinct stress-activated signaling cascade that couples cellular stress to c-Jun phosphorylation. In vitro kinase assay, dominant-negative mutant expression, in vivo pathway epistasis Nature High 7997269
1996 Ceramide initiates apoptosis through the SAPK/JNK cascade, providing evidence that ceramide-generated second messenger signals are integrated with cytokine- and stress-activated apoptotic pathways via SAPK/JNK activation. Cell-based apoptosis assays with ceramide treatment, SAPK/JNK activity measurements, pharmacological and genetic inhibition of SAPK pathway Nature Medium 8598911
1996 MLK-3 (Mixed Lineage Kinase-3) activates SAPK/JNK through direct phosphorylation of SEK1 in vitro, and co-precipitates with SEK1, placing MLK-3 as an upstream MAPKKK in the SAPK/JNK cascade downstream of Ste20-like kinases. In vitro kinase assay (immunoprecipitated MLK-3 phosphorylating SEK1), co-precipitation, dominant-negative epistasis The EMBO journal High 9003778
1997 TNF-R1-mediated activation of SAPK/JNK occurs through a noncytotoxic TRAF2-dependent pathway. TRAF2 is both sufficient and necessary for SAPK activation by TNF-R1, and this pathway is distinct from the FADD-dependent apoptotic pathway. Dominant-negative TRAF2 and FADD mutant expression, SAPK activity assays, epistasis Science High 8985011
1997 MKK7 was identified as a novel SAPK/JNK-specific kinase (MAPKK). Unlike SEK1/MKK4 which activates both SAPK/JNK and p38, MKK7 is specific for the SAPK/JNK subgroup. MKK7 is a major SAPK/JNK-activating kinase in osmotically shocked cells and a major activator of SAPK/JNK in the TNF-alpha-stimulated pathway. Molecular cloning, immunochemical identification, in vitro kinase specificity assays, column fractionation, AP-1 reporter assays The EMBO journal High 9384583
1998 Germinal center kinase (GCK) couples TRAF2 to MEKK1 and thereby to SAPK/JNK activation downstream of TNF-R1. GCK interacts in vivo with TRAF2 and MEKK1. Separately, RIP associates with an endogenous MAPKKK upstream of the p38 pathway, demonstrating two distinct proximal kinase branches downstream of TRAF2. Co-immunoprecipitation (in vivo interaction), in vitro kinase assays, epistasis by overexpression The Journal of biological chemistry Medium 9712898
1999 JNK1 and JNK2 together are required for region-specific apoptosis during early brain development. Jnk1/Jnk2 double-knockout mice are embryonic lethal with severe dysregulation of apoptosis in the brain: reduced cell death in hindbrain neuroepithelium prior to neural tube closure and increased apoptosis with caspase activation in the forebrain. Knockout mouse genetics, histology, caspase activity assays, apoptosis quantification Neuron High 10230788
1999 JNK2 is essential for efficient T-cell activation: Jnk2-/- mice show defective peripheral T-cell proliferation and reduced IL-2, IL-4, and IFN-gamma production after anti-CD3 stimulation. JNK2 is also required for anti-CD3-induced apoptosis of immature (CD4+CD8+) thymocytes but not for apoptosis induced by anti-Fas, dexamethasone, or UV-C. B-cell activation is normal in JNK2-deficient mice. Jnk2 knockout mice, T-cell proliferation assays, cytokine production assays (IL-2, IL-4, IFN-gamma), apoptosis assays with multiple stimuli Current biology : CB High 10021384
1999 Jnk1/Jnk2 double-knockout mice die around embryonic day 11 with open neural tube (exencephaly) at hindbrain level and altered apoptosis: reduced apoptosis in hindbrain neuroepithelium at E9.25, then dramatically increased cell death at E10.5 in both hindbrain and forebrain. About 25% of jnk1-/-jnk2+/- fetuses display exencephaly, while jnk1+/-jnk2-/- mice are viable, indicating dose-dependency. Knockout mouse genetics (single and compound), embryological analysis, TUNEL assay Mechanisms of development High 10559486
2000 In response to ionizing radiation, SAPK/JNK translocates to mitochondria and associates with the anti-apoptotic protein Bcl-x(L). SAPK phosphorylates Bcl-x(L) on Thr-47 and Thr-115 in vitro and in vivo. A Bcl-x(L) mutant with both threonines substituted by alanines (Ala-47, Ala-115) is a more potent inhibitor of ionizing radiation-induced apoptosis than wild-type Bcl-x(L), demonstrating that SAPK-mediated phosphorylation of Bcl-x(L) attenuates its anti-apoptotic function. Subcellular fractionation/translocation assay, co-immunoprecipitation, in vitro and in vivo kinase assay, site-directed mutagenesis of Bcl-x(L), apoptosis assay with mutant rescue The Journal of biological chemistry High 10617621
2001 MKP-7, a novel dual-specificity phosphatase, binds to and inactivates SAPK/JNK and p38alpha/beta MAPKs but not ERK. MKP-7 is predominantly cytoplasmic, distinguishing it from hVH5 (which is nuclear and cytoplasmic). MKP-7 shows isoform specificity within the p38 family, inactivating p38alpha and p38beta but not p38gamma or delta. Molecular cloning, in vitro phosphatase activity assay, co-immunoprecipitation/binding assay, subcellular localization The Journal of biological chemistry High 11359773
2002 PKCdelta is required for SAPK/JNK activation in response to DNA damage (araC and other genotoxins). PKCdelta activates SAPK through an MKK7-dependent, SEK1-independent mechanism. The pathway is: Lyn tyrosine kinase → PKCdelta → MEKK1 → MKK7 → SAPK. Pharmacological inhibition (rottlerin), kinase-inactive PKCdelta mutant, siRNA knockdown, co-expression epistasis assays The Journal of biological chemistry Medium 12377781
2003 SAPK/JNK directly phosphorylates the cdc2 regulator cdc25c on serine 168 (S168) in vitro. This phosphorylation inhibits cdc25c phosphatase activity in cells. A S168A cdc25c mutant reverses SAPK-induced inhibition of cdc2/cyclin B kinase activity, establishing a novel mechanism by which SAPK regulates the G2/M transition through inhibitory phosphorylation of cdc25c. In vitro kinase assay (direct phosphorylation of cdc25c), site-directed mutagenesis (S168A), phospho-specific antibody, cdc2/cyclin B kinase activity assay, mutant rescue Cellular signalling High 12742231
2004 JNK2 and JNK1 have distinct and opposing roles in regulating c-Jun and cell proliferation. In unstimulated cells, JNK2 is preferentially bound to c-Jun and promotes c-Jun degradation, making JNK2 a negative regulator of c-Jun stability and cellular proliferation. In contrast, JNK1 becomes the major c-Jun interacting kinase after cell stimulation and promotes c-Jun phosphorylation and stability. Jnk2-/- fibroblasts exhibit elevated c-Jun phosphorylation and stability with accelerated G1/S transition; Jnk1-/- cells show the inverse. Re-expression of JNK2 in Jnk2-/- cells reverses the phenotype. Jnk1 and Jnk2 knockout fibroblasts and erythroblasts, cell cycle analysis (BrdU incorporation), co-immunoprecipitation, c-Jun stability assays, rescue by re-expression Molecular cell High 15350216
2004 JNK2 is required for scavenger receptor A (SR-A)-mediated foam cell formation in atherosclerosis. JNK2-deficient macrophages display suppressed foam cell formation due to defective uptake and degradation of modified lipoproteins. SR-A phosphorylation is markedly decreased in JNK2-deficient macrophages. Macrophage-restricted deletion of JNK2 is sufficient to decrease atherogenesis in ApoE-/- mice. Jnk2 knockout and macrophage-specific conditional knockout in ApoE-/- mice, foam cell formation assays, SR-A phosphorylation assay, lipoprotein uptake assays Science High 15567863
2004 Inhibition of JNK2 (but not JNK1) by dominant-negative mutant, pharmacological inhibitor, or RNAi causes accumulation of mammalian cells with 4N DNA content. Cells progress normally to metaphase but exhibit defects in central spindle formation and chromosome segregation during anaphase, leading to polyploidy. CDK1 activity, cyclin B1, and PLK1 turnover remain intact, indicating JNK2 regulates anaphase through a CDK1/cyclin B1-independent mechanism. Dominant-negative JNK2 expression, pharmacological JNK inhibition, RNAi, flow cytometry (DNA content), immunofluorescence microscopy of mitotic cells The Journal of biological chemistry Medium 15262983
2005 Disruption of Mapk9 (encoding JNK2) in non-obese diabetic mice decreases destructive insulitis and reduces progression to type 1 diabetes. CD4+ T cells from JNK2-deficient NOD mice produce less IFN-gamma but increased IL-4 and IL-5, indicating JNK2 controls Th1/Th2 balance of the immune response. Jnk2 (Mapk9) knockout in NOD mice, insulitis scoring, diabetes incidence monitoring, cytokine production assays (ELISA/intracellular staining) PNAS High 15867147
2005 During glucose deprivation, SEK1 phosphorylates JNK2 on Tyr-185 after being activated by ASK1 (via JIP3 scaffold). Phosphorylated JNK2 then binds JIP1 scaffold, whereupon Thr-183 of JNK2 is phosphorylated. JNK2 phosphorylates JIP1 on Thr-103, causing dissociation of Akt1 from JIP1. Released Akt1 then inhibits SEK1 and ASK1 through phosphorylation, forming a negative feedback loop. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis (phosphorylation sites), siRNA knockdown, overexpression The Journal of biological chemistry Medium 15911620
2006 Using a chemical genetic approach, both JNK1 and JNK2 are shown to be positive regulators of cJun expression and cell proliferation. The previously reported opposing phenotypes of Jnk1 and Jnk2 knockout mice are explained by competition between the two isoforms rather than inherently opposite activities. Chemical genetic (analog-sensitive kinase) approach, Jnk1 and Jnk2 knockout fibroblasts, c-Jun expression/phosphorylation assays Molecular cell High 16973441
2006 CARMA1 and Bcl10 selectively regulate JNK2 (but not JNK1) in the TCR-signaling pathway. Bcl10 inducibly associates with JNK2 and functions as a JIP-like scaffold to assemble JNK2, MKK7, and TAK1. This CARMA1/Bcl10-mediated JNK2 activation regulates c-Jun protein levels after TCR stimulation. Knockout mice (CARMA1-/-, Bcl10-/-), co-immunoprecipitation, isoform-selective JNK assays, c-Jun expression analysis Immunity High 17189706
2007 JNK1 and JNK2 cooperatively phosphorylate p53 at Ser6 to induce apoptosis downstream of FDH. JNK2 (but not JNK1) physically associates with p53 by pulldown assay. JNK1 phosphorylates JNK2 before JNK2 directly phosphorylates p53 at Ser6, defining a sequential JNK1→JNK2→p53 signaling mechanism. siRNA knockdown of JNK1 and JNK2, pharmacological JNK inhibition (SP600125), p53-specific pulldown assay, phospho-specific assays, rescue by overexpression Oncogene Medium 17525747
2008 JNK2 regulates SIRT1 protein stability through phosphorylation at serine 27. RNAi-mediated depletion of JNK2 reduced the half-life of SIRT1 from >9 h to <2 h, correlating with loss of SIRT1 phosphorylation at Ser27. Depletion of JNK1 had no effect on SIRT1 stability. Phosphorylation at Ser47 showed no correlation with stability. RNAi knockdown of JNK1 and JNK2, SIRT1 protein half-life measurement (pulse-chase), phosphorylation site-specific analysis Cell cycle Medium 18838864
2009 JNK2 inhibits hepatocyte cell death by blocking the mitochondrial death pathway. jnk2 knockdown in high-fat diet-fed mice increased liver injury in concert with increased expression of pro-apoptotic Bcl-2 family members Bim and Bax, with increased injury resulting in part from Bim-dependent activation of the mitochondrial death pathway. This is mechanistically distinct from JNK1, which promotes steatosis. Antisense oligonucleotide knockdown of jnk1 and jnk2 in vivo, liver injury assays, Bcl-2 family member expression analysis, genetic epistasis with Bim Hepatology Medium 19053047
2009 JNK2 promotes degradation of ABCG1 (ATP-binding cassette transporter G1) through serine phosphorylation, leading to proteasomal degradation of the transporter and reduced cholesterol efflux. JNK2-deficient (but not JNK1-deficient) macrophages are resistant to 12S-HETE-mediated ABCG1 protein downregulation and show increased cholesterol efflux. JNK1, JNK2, and MKK3 knockout macrophages, pharmacological inhibition, dominant-negative constructs, proteasome inhibitor rescue, cholesterol efflux assays The Journal of biological chemistry Medium 19713213
2009 JNK2 suppresses a basal JNK1/c-Jun/Bcl-3 apoptotic network in cancer cells. Silencing JNK2 by RNAi results in JNK1-dependent apoptosis of cancer cells via upregulation of hypo-phosphorylated c-Jun, which auto-regulates its own expression and suppresses Bcl-3 (an IκB protein), leading to basal apoptosis via components of the TNFα response pathway. Combinatorial RNAi plus gene knockout, phosphorylation mutant expression, chromatin immunoprecipitation, apoptosis assays PloS one Medium 19806201
2009 Activated JNK2 increases GSK3beta activity and inhibits beta-catenin expression and transcriptional activity. JNK2-mediated beta-catenin downregulation is blocked by proteasome inhibitor MG132 and GSK3beta inhibitor LiCl, and by GSK3beta phosphorylation site mutations (Ser33/Ser37) in beta-catenin. Physical interaction among JNK2, beta-catenin, and GSK3beta was demonstrated by co-immunoprecipitation, two-hybrid assay, and confocal microscopy. JNK2-/- mice show elevated beta-catenin and increased GSK3beta phosphorylation in intestinal epithelial cells. In vitro JNK2 activation, GSK3beta activity assay, proteasome/GSK3beta inhibitor rescue, site-directed mutagenesis of beta-catenin, co-IP, mammalian two-hybrid assay, confocal co-localization, JNK2-/- mice PloS one Medium 19675674
2011 JNK2 promotes mammary cancer cell migration through inhibition of EPS8 (epidermal growth factor substrate 8) expression. In jnk2-/- mammary tumors, EPS8 expression is higher. Absence of JNK2 reduces cell migration that is rescued by EPS8 knockdown. JNK2 enhances formation of the EPS8-Abi-1-Sos-1 complex to augment EGFR activation of Akt and ERK; absence of JNK2 promotes EPS8/RN-Tre association to inhibit EGFR endocytic trafficking. Jnk2 knockout mice and mammary tumor cells, co-immunoprecipitation, EPS8 knockdown rescue, migration assays, EGFR trafficking assays The Journal of biological chemistry Medium 21357683
2011 JNK2-selective peptide inhibitors (JIP10-Δ-TAT(i) and JIP10-Δ-R9) inhibit JNK2 with IC50 ~90 nM and 10-fold selectivity over JNK1 and JNK3. These inhibitors block migration of PyVMT cancer cells in a JNK2-dependent manner: they inhibit migration of jnk2+/+ cells and jnk2-/- cells re-expressing GFP-JNK2, but not jnk2-/- cells alone. In vitro kinase assay (IC50 determination), cell-based JNK and c-Jun phosphorylation assays, JNK2 knockout cell migration assays, GFP-JNK2 rescue ACS chemical biology Medium 21438496
2012 JNK2 and JNK3 are the major JNK isoforms activated in retinal ganglion cell (RGC) axons immediately after injury. Combined deficiency of Jnk2 and Jnk3 provides robust long-term protection against axonal injury-induced RGC death and prevents JUN phosphorylation and BRN3B downregulation. JNK2 and JNK3 but not JNK1 are activated in injured axons. Jnk isoform-specific knockout mice (single and double), axonal injury model (optic nerve crush), RGC survival counting, JUN phosphorylation and BRN3B marker analysis Neurobiology of disease High 22353563
2012 JNK2 is activated during ER stress and promotes cell survival by regulating the unfolded protein response (UPR). Silencing or pharmacological inhibition of JNK2 delays BiP upregulation, causes earlier/greater CHOP expression, and leads to p62 accumulation, acidic compartment accumulation, caspase-3 activation, and apoptosis. JNK2 prevents pathological accumulation of the acidic compartment during autophagic flux. Pharmacological inhibition, siRNA silencing of JNK2, UPR marker analysis (BiP, CHOP), autophagy marker (p62), caspase-3 activation, lysosomal assays Cell death & disease Medium 23171849
2012 EGFR-inhibition by cetuximab induces JNK2 phosphorylation through JIP-4 (JNK-interacting protein 4), identified by immunoprecipitation-mass spectrometry. This JIP-4/JNK2 signaling bypass attenuates cetuximab-mediated radiosensitization; knockdown of JIP-4 or JNK2 enhances cetuximab efficacy and tumor cell radiosensitivity. Phosphoproteome arrays, immunoprecipitation-mass spectrometry, JIP-4 and JNK2 knockdown, clonogenic survival assays, 3D cell culture and xenograft models Cancer research Medium 23074283
2014 MAVS specifically activates JNK2 (but not JNK1 or other MAP kinases) during viral infection via a MAVS-MKK7-JNK2 signaling axis. MAVS recruits MKK7 onto mitochondria via its 3D domain, which subsequently phosphorylates JNK2 to activate apoptosis. Jnk2-/- cells (but not Jnk1-/- cells) and Mkk7-/- cells fail to initiate virus-induced apoptosis. Jnk2-/- mice show marked inflammatory injury in lung and liver after viral challenge. Jnk1, Jnk2, Mkk7 knockout cells and mice, MAVS domain mapping, co-immunoprecipitation of MAVS with MKK7, viral infection apoptosis assays, in vivo challenge model PLoS pathogens High 24651600
2014 JNK2 (but not JNK1) specifically activates pro-survival autophagy in response to palmitic acid in hepatocytes. Specific knockdown of JNK2 suppresses PA-induced autophagy and enhances pro-apoptotic activity, while JNK1 knockdown has the converse effect (promoting lipoapoptosis when JNK2 is absent). Isoform-specific siRNA knockdown of JNK1 and JNK2, autophagy markers (LC3-II, Beclin1, Atg5), apoptosis assays (Annexin V, PARP cleavage), pharmacological JNK inhibition Acta pharmacologica Sinica Medium 24608675
2015 JNK2 has a crucial role in G2-specific Golgi stack separation through direct phosphorylation of GRASP65 (also known as GORASP1) at Ser277. Inhibition of JNK2 by RNAi or three unrelated JNK inhibitors causes a potent G2 cell cycle block. JNK activity becomes dispensable for mitotic entry if the Golgi complex is disassembled by brefeldin A or GRASP65 depletion. FRAP demonstrates JNK is required for cleavage of tubules connecting Golgi stacks. RNAi, pharmacological JNK inhibition (three inhibitors), cell cycle analysis, GRASP65 site-directed mutagenesis (Ser277), brefeldin A treatment, FRAP microscopy Journal of cell science High 25948586
2015 X-ray crystallography of JNK2/3 complexed with aminopyrazole inhibitors, combined with site-directed mutagenesis, identified residue L144 in JNK3 as a key determinant of isoform selectivity for JNK2/3 over JNK1. JNK2/3-selective inhibitors protected human dopaminergic neurons against 6-OHDA-induced ROS generation and mitochondrial membrane potential depolarization. X-ray crystallography, site-directed mutagenesis (L144), in vitro kinase selectivity assays (IC50), ROS measurement, mitochondrial membrane potential assay in dopaminergic neurons Scientific reports High 25623238
2016 JNK2 activates PHD1 (prolyl hydroxylase 1) in docetaxel-treated cancer cells under hypoxia, leading to PHD1-mediated hydroxylation and subsequent proteasomal degradation of HIF-1α. JNK2 knockdown by siRNA blocks docetaxel-induced HIF-1α degradation and cancer cell death by inhibiting PHD1 activation. siRNA knockdown of JNK2 and PHD1, proteasome inhibitor rescue, luciferase HIF-1 reporter assay, xenograft tumor model Scientific reports Medium 27263528
2018 JNK2 activates CaMKII (Ca2+/calmodulin-dependent kinase II) in aged atria, which in turn upregulates diastolic sarcoplasmic reticulum Ca2+ leak via RyR2 channels, leading to aberrant intracellular Ca2+ waves and enhanced atrial fibrillation propensity. This JNK2-CaMKII-RyR2 proarrhythmic pathway is absent in young atria and is eliminated by JNK2 ablation or CaMKII inhibition. Transgenic mouse models (JNK2 ablation), electrophysiology, Ca2+ imaging, biochemical CaMKII activation assays, human donor heart studies, JNK2-specific inhibition Circulation research High 29352041
2018 JNK2 activation up-regulates CaMKIIδ expression in the aged atrium at the transcriptional level through the downstream transcription factor c-jun. JNK2 (but not JNK1) activation increases CaMKIIδ mRNA and protein. Increased c-jun phosphorylation and c-jun binding to the CaMKIIδ promoter (shown by ChIP) is required; JNK2 siRNA or c-jun siRNA knockdown completely reverses this. AdMKK7D-JNK2 vs AdMKK7D-JNK1 overexpression, JNK2-specific inhibitors, dominant-negative JNK2, chromatin immunoprecipitation (ChIP), CaMKIIδ promoter-luciferase assay, siRNA knockdown Cardiovascular research High 29360953
2020 JNK2 (but not JNK1) increases SERCA2 (SR Ca2+-ATPase) activity and consequently elevates SR Ca2+ content load. JNK2 associates with and phosphorylates SERCA2 protein. JNK2 increases SERCA2-ATPase maximal rate without altering Ca2+ affinity. This JNK2-driven SERCA2 activation is CaMKII-independent and, combined with JNK2-CaMKII-driven SR Ca2+ leak, exacerbates arrhythmic SR Ca2+ dynamics. Confocal Ca2+ imaging, biochemical co-immunoprecipitation and phosphorylation assays, ATPase activity assay, dual Ca2+/voltage optical mapping, genetic models (JNK2 ablation), CaMKII inhibition Circulation research High 33334123

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1996 Requirement for ceramide-initiated SAPK/JNK signalling in stress-induced apoptosis. Nature 1680 8598911
1994 Role of SAPK/ERK kinase-1 in the stress-activated pathway regulating transcription factor c-Jun. Nature 967 7997269
1999 The Jnk1 and Jnk2 protein kinases are required for regional specific apoptosis during early brain development. Neuron 762 10230788
1994 JNK2 contains a specificity-determining region responsible for efficient c-Jun binding and phosphorylation. Genes & development 591 8001819
1999 Induction of GADD45 and JNK/SAPK-dependent apoptosis following inducible expression of BRCA1. Cell 502 10367887
1997 Activation of SAPK/JNK by TNF receptor 1 through a noncytotoxic TRAF2-dependent pathway. Science (New York, N.Y.) 407 8985011
2000 Translocation of SAPK/JNK to mitochondria and interaction with Bcl-x(L) in response to DNA damage. The Journal of biological chemistry 374 10617621
2004 Distinct roles for JNK1 and JNK2 in regulating JNK activity and c-Jun-dependent cell proliferation. Molecular cell 332 15350216
2006 JNK1 but not JNK2 promotes the development of steatohepatitis in mice. Hepatology (Baltimore, Md.) 314 16374858
1999 Defective neural tube morphogenesis and altered apoptosis in the absence of both JNK1 and JNK2. Mechanisms of development 296 10559486
1996 MLK-3 activates the SAPK/JNK and p38/RK pathways via SEK1 and MKK3/6. The EMBO journal 281 9003778
2006 Functional in vivo interactions between JNK1 and JNK2 isoforms in obesity and insulin resistance. Proceedings of the National Academy of Sciences of the United States of America 279 16818881
1999 JNK2 is required for efficient T-cell activation and apoptosis but not for normal lymphocyte development. Current biology : CB 250 10021384
2004 Requirement of JNK2 for scavenger receptor A-mediated foam cell formation in atherogenesis. Science (New York, N.Y.) 235 15567863
1997 A novel SAPK/JNK kinase, MKK7, stimulated by TNFalpha and cellular stresses. The EMBO journal 232 9384583
1998 Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38. The Journal of biological chemistry 227 9712898
1996 Human HPK1, a novel human hematopoietic progenitor kinase that activates the JNK/SAPK kinase cascade. Genes & development 222 8824585
1995 Activation of the SAPK pathway by the human STE20 homologue germinal centre kinase. Nature 210 7477268
1996 HPK1, a hematopoietic protein kinase activating the SAPK/JNK pathway. The EMBO journal 205 9003777
2009 Differential effects of JNK1 and JNK2 inhibition on murine steatohepatitis and insulin resistance. Hepatology (Baltimore, Md.) 189 19053047
1999 Alkyl-lysophospholipids activate the SAPK/JNK pathway and enhance radiation-induced apoptosis. Cancer research 151 10344758
2006 JNK2 is a positive regulator of the cJun transcription factor. Molecular cell 141 16973441
2001 A Novel MAPK phosphatase MKP-7 acts preferentially on JNK/SAPK and p38 alpha and beta MAPKs. The Journal of biological chemistry 137 11359773
2012 JNK2 and JNK3 are major regulators of axonal injury-induced retinal ganglion cell death. Neurobiology of disease 124 22353563
2002 c-Jun NH(2)-terminal kinase (JNK)1 and JNK2 have distinct roles in CD8(+) T cell activation. The Journal of experimental medicine 122 11927626
1997 Bruton's tyrosine kinase regulates apoptosis and JNK/SAPK kinase activity. Proceedings of the National Academy of Sciences of the United States of America 120 9108083
2007 Cooperation between JNK1 and JNK2 in activation of p53 apoptotic pathway. Oncogene 116 17525747
1999 Sending signals from the synapse to the nucleus: possible roles for CaMK, Ras/ERK, and SAPK pathways in the regulation of synaptic plasticity and neuronal growth. Journal of neuroscience research 113 10491574
2004 Physiological roles of SAPK/JNK signaling pathway. Journal of biochemistry 111 15496581
2008 JNK2-dependent regulation of SIRT1 protein stability. Cell cycle (Georgetown, Tex.) 110 18838864
2001 The p38 SAPK pathway regulates the expression of the MMP-9 collagenase via AP-1-dependent promoter activation. Experimental cell research 98 11716547
1999 Protein kinase Ctheta, a selective upstream regulator of JNK/SAPK and IL-2 promoter activation in Jurkat T cells. European journal of immunology 98 9933094
2002 Differential effects of JNK1 and JNK2 on signal specific induction of apoptosis. Oncogene 91 11948429
2006 Expression and distribution of JNK/SAPK-associated scaffold protein JSAP1 in developing and adult mouse brain. Journal of neurochemistry 89 16606357
2006 The CARMA1-Bcl10 signaling complex selectively regulates JNK2 kinase in the T cell receptor-signaling pathway. Immunity 88 17189706
1999 Quinone reductase inhibitors block SAPK/JNK and NFkappaB pathways and potentiate apoptosis. The Journal of biological chemistry 83 10531305
2015 Inflammation-induced ROS generation causes pancreatic cell death through modulation of Nrf2/NF-κB and SAPK/JNK pathway. Free radical research 81 26189548
2015 Combined Activities of JNK1 and JNK2 in Hepatocytes Protect Against Toxic Liver Injury. Gastroenterology 79 26708719
1998 The role of the stress-activated protein kinase (SAPK/JNK) signaling pathway in radiation-induced apoptosis. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 78 9681884
2004 JNK2: a negative regulator of cellular proliferation. Cell cycle (Georgetown, Tex.) 75 15611655
2018 Stress Signaling JNK2 Crosstalk With CaMKII Underlies Enhanced Atrial Arrhythmogenesis. Circulation research 74 29352041
2012 EGFR/JIP-4/JNK2 signaling attenuates cetuximab-mediated radiosensitization of squamous cell carcinoma cells. Cancer research 74 23074283
2005 Disruption of the Jnk2 (Mapk9) gene reduces destructive insulitis and diabetes in a mouse model of type I diabetes. Proceedings of the National Academy of Sciences of the United States of America 74 15867147
2012 Coordinated control of replication and transcription by a SAPK protects genomic integrity. Nature 72 23178807
2002 Activation of SAPK/JNK signaling by protein kinase Cdelta in response to DNA damage. The Journal of biological chemistry 70 12377781
2001 Induction of the SAPK activator MIG-6 by the alkylating agent methyl methanesulfonate. Molecular carcinogenesis 68 11429782
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
2014 Palmitic acid induces autophagy in hepatocytes via JNK2 activation. Acta pharmacologica Sinica 63 24608675
2002 Discovery of CEP-1347/KT-7515, an inhibitor of the JNK/SAPK pathway for the treatment of neurodegenerative diseases. Progress in medicinal chemistry 63 12516522
2013 SAPK pathways and p53 cooperatively regulate PLK4 activity and centrosome integrity under stress. Nature communications 62 23653187
1997 A role for JNK/SAPK in proliferation, but not apoptosis, of IL-3-dependent cells. Current biology : CB 61 9382802
2012 JNK2 is activated during ER stress and promotes cell survival. Cell death & disease 59 23171849
2008 Pro-inflammatory cytokine-induced SAPK/MAPK and JAK/STAT in rheumatoid arthritis and the new anti-depression drugs. Expert opinion on therapeutic targets 59 18208366
2003 Oxidative stress and neuronal adaptation in Alzheimer disease: the role of SAPK pathways. Antioxidants & redox signaling 57 14580312
2000 Protein kinase activation by warm and cold hypoxia- reoxygenation in primary-cultured rat hepatocytes-JNK(1)/SAPK(1) involvement in apoptosis. Hepatology (Baltimore, Md.) 57 11050053
2008 Mechanism of copper-activated transcription: activation of AP-1, and the JNK/SAPK and p38 signal transduction pathways. Journal of molecular biology 56 18793645
2006 Release of RASSF1C from the nucleus by Daxx degradation links DNA damage and SAPK/JNK activation. The EMBO journal 56 16810318
2015 JNK2 controls fragmentation of the Golgi complex and the G2/M transition through phosphorylation of GRASP65. Journal of cell science 55 25948586
2001 The p38-MAPK/SAPK pathway is required for human keratinocyte migration on dermal collagen. The Journal of investigative dermatology 55 11886529
1999 Activation of the p38 and JNK/SAPK mitogen-activated protein kinase pathways during apoptosis is mediated by a novel retinoid. Experimental cell research 54 10047465
1999 Okadaic acid and anisomycin are protective and stimulate the SAPK/JNK pathway. Journal of cardiovascular pharmacology 50 10445668
2012 Fucoxanthin induces GADD45A expression and G1 arrest with SAPK/JNK activation in LNCap human prostate cancer cells. Anticancer research 47 22399598
2017 Moscatilin induces apoptosis of pancreatic cancer cells via reactive oxygen species and the JNK/SAPK pathway. Molecular medicine reports 46 28138710
2003 Induction of apoptosis through the activation of SAPK/JNK followed by the expression of death receptor Fas in X-irradiated cells. Journal of radiation research 46 14646222
2003 Aluminum-induced apoptosis in cultured cortical neurons and its effect on SAPK/JNK signal transduction pathway. Brain research 45 12865155
2020 JNK2, a Newly-Identified SERCA2 Enhancer, Augments an Arrhythmic [Ca2+]SR Leak-Load Relationship. Circulation research 43 33334123
2014 MAVS-MKK7-JNK2 defines a novel apoptotic signaling pathway during viral infection. PLoS pathogens 43 24651600
2016 Inhibition of EZH2 via activation of SAPK/JNK and reduction of p65 and DNMT1 as a novel mechanism in inhibition of human lung cancer cells by polyphyllin I. Journal of experimental & clinical cancer research : CR 39 27421653
2019 TNF-α Drives the CCL4 Expression in Human Monocytic Cells: Involvement of the SAPK/JNK and NF-κB Signaling Pathways. Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology 38 30964608
2011 Development of JNK2-selective peptide inhibitors that inhibit breast cancer cell migration. ACS chemical biology 38 21438496
2010 The p38 SAPK is recruited to chromatin via its interaction with transcription factors. The Journal of biological chemistry 37 20682780
2003 SAPK/JNK regulates cdc2/cyclin B kinase through phosphorylation and inhibition of cdc25c. Cellular signalling 37 12742231
2018 Transcriptional regulation of stress kinase JNK2 in pro-arrhythmic CaMKIIδ expression in the aged atrium. Cardiovascular research 36 29360953
2009 Murine 12/15-lipoxygenase regulates ATP-binding cassette transporter G1 protein degradation through p38- and JNK2-dependent pathways. The Journal of biological chemistry 36 19713213
2016 Docetaxel induced-JNK2/PHD1 signaling pathway increases degradation of HIF-1α and causes cancer cell death under hypoxia. Scientific reports 35 27263528
2003 Src-CrkII-C3G-dependent activation of Rap1 switches growth hormone-stimulated p44/42 MAP kinase and JNK/SAPK activities. The Journal of biological chemistry 35 12734187
2018 TGF-β downregulation-induced cancer cell death is finely regulated by the SAPK signaling cascade. Experimental & molecular medicine 34 30523245
2005 Cross-talk between JIP3 and JIP1 during glucose deprivation: SEK1-JNK2 and Akt1 act as mediators. The Journal of biological chemistry 33 15911620
2010 p27 suppresses arsenite-induced Hsp27/Hsp70 expression through inhibiting JNK2/c-Jun- and HSF-1-dependent pathways. The Journal of biological chemistry 32 20566634
2009 GSK3beta is involved in JNK2-mediated beta-catenin inhibition. PloS one 32 19675674
2009 Basal cancer cell survival involves JNK2 suppression of a novel JNK1/c-Jun/Bcl-3 apoptotic network. PloS one 32 19806201
2020 Tanshinone IIA prevents platelet activation and down-regulates CD36 and MKK4/JNK2 signaling pathway. BMC cardiovascular disorders 31 32059638
2006 Coordination of JNK1 and JNK2 is critical for GADD45alpha induction and its mediated cell apoptosis in arsenite responses. The Journal of biological chemistry 31 16973625
2017 RhoGDIβ promotes Sp1/MMP-2 expression and bladder cancer invasion through perturbing miR-200c-targeted JNK2 protein translation. Molecular oncology 30 28846829
2007 Anti endothelial cell autoantibodies selectively activate SAPK/JNK signalling in Wegener's granulomatosis. Journal of the American Society of Nephrology : JASN 29 17699811
2004 Inhibition of JNK2 disrupts anaphase and produces aneuploidy in mammalian cells. The Journal of biological chemistry 29 15262983
2000 Cloning of DPK, a novel dendritic cell-derived protein kinase activating the ERK1/ERK2 and JNK/SAPK pathways. Biochemical and biophysical research communications 29 10924369
2018 Anti-JNK2 peptide-siRNA nanostructures improve plaque endothelium and reduce thrombotic risk in atherosclerotic mice. International journal of nanomedicine 28 30233180
2011 Differential regulation of CIDEA and CIDEC expression by insulin via Akt1/2- and JNK2-dependent pathways in human adipocytes. Journal of lipid research 28 21636835
2012 Increased hepatic fibrosis and JNK2-dependent liver injury in mice exhibiting hepatocyte-specific deletion of cFLIP. American journal of physiology. Gastrointestinal and liver physiology 27 22700824
2011 c-Jun N-terminal kinase 2 (JNK2) enhances cell migration through epidermal growth factor substrate 8 (EPS8). The Journal of biological chemistry 27 21357683
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
2016 Rac1b enhances cell survival through activation of the JNK2/c-JUN/Cyclin-D1 and AKT2/MCL1 pathways. Oncotarget 26 26918455
1996 Activation of JNK/SAPK pathway is not directly inhibitory for cell cycle progression in NIH3T3 cells. Oncogene 26 8957084
2015 Structural basis and biological consequences for JNK2/3 isoform selective aminopyrazoles. Scientific reports 25 25623238
2009 Involvement of the c-jun N-terminal kinases JNK1 and JNK2 in complement-mediated cell death. Molecular immunology 25 19864026
2005 Late activation of stress kinases (SAPK/JNK) by genotoxins requires the DNA repair proteins DNA-PKcs and CSB. Molecular biology of the cell 25 16319174
2021 Protective effects of 6-gingerol on 6-hydroxydopamine-induced apoptosis in PC12 cells through modulation of SAPK/JNK and survivin activation. Journal of biochemical and molecular toxicology 24 34783140
2019 Involvement of SAPK/JNK Signaling Pathway in Copper Enhanced Zinc-Induced Neuronal Cell Death. Toxicological sciences : an official journal of the Society of Toxicology 24 30768131
2019 Silibinin inhibited autophagy and mitochondrial apoptosis in pancreatic carcinoma by activating JNK/SAPK signaling. Pathology, research and practice 24 31351801

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