Affinage

MAPK6

Mitogen-activated protein kinase 6 · UniProt Q16659

Length
721 aa
Mass
82.7 kDa
Annotated
2026-06-10
100 papers in source corpus 44 papers cited in narrative 44 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAPK6 (ERK3) is an atypical mitogen-activated protein kinase that functions as a constitutively active signaling kinase whose biology is dominated by its activation loop, its regulated nucleocytoplasmic distribution, and its tightly controlled protein stability (PMID:8621539, PMID:12915405). Unlike conventional MAP kinases, ERK3 carries a single phospho-acceptor (Ser189) in its SEG activation loop that is phosphorylated by a dedicated upstream activity rather than by MEK; group I PAKs (PAK1/2/3) directly phosphorylate Ser189 downstream of Rac1, stimulating intrinsic catalytic activity (PMID:21177870, PMID:21317288, PMID:8662649), while DUSP2 reverses this phosphorylation and damps signaling (PMID:28252035). ERK3 shuttles between nucleus and cytoplasm via CRM1-dependent export, and this shuttling is required for its effects on cell cycle progression (PMID:12915405). Its principal effector axis is a kinase-scaffold complex with MK5/PRAK formed through the non-canonical FRIEDE docking motif in the C-terminal L16 extension; complex formation depends on Ser189 phosphorylation and drives MK5 activation and co-redistribution to the cytoplasm, with ERK3 and MK5 mutually stabilizing one another (PMID:15577943, PMID:15538386, PMID:18720373, PMID:19473979). Through this module ERK3 controls myogenic differentiation via MK5-mediated FoxO3 phosphorylation (PMID:35141958) and adipocyte lipolysis via a FOXO1/ATGL program (PMID:32139423). Beyond MK5, ERK3 directly phosphorylates substrates governing the cytoskeleton and cell division — supervillin at Ser245 to enable cytokinesis (PMID:36576983), and ARP3 at Ser418 while acting as a CDC42 GEF to drive actin polymerization and filopodia formation (PMID:37057894) — and phosphorylates SRC-3 at Ser857 to promote MMP expression and cancer cell invasion (PMID:22505454, PMID:30166347). ERK3 abundance is rate-limiting and is set by multiple degradative routes, including FBXW7- and TRIM21-mediated proteasomal degradation (PMID:35022544, PMID:39763069), chaperone-mediated autophagy through HSC70/LAMP2A that is antagonized by EGLN3 hydroxylation (PMID:35124697), and intracellular pH sensing through its C-terminus (PMID:41123996); conversely, Cdk1 phosphorylation of four C-terminal sites stabilizes ERK3 during mitosis (PMID:20236090).

Mechanistic history

Synthesis pass · year-by-year structured walk · 18 steps
  1. 1996 High

    Establishing ERK3 as an atypical MAP kinase required defining its activation site and constitutive localization, distinguishing it from classical ERKs.

    Evidence In vitro kinase assays with D171A/S189 mutants plus subcellular fractionation and immunofluorescence

    PMID:8621539

    Open questions at the time
    • Did not identify the physiological upstream kinase for Ser189
    • No substrate beyond autophosphorylation identified at this stage
  2. 1996 High

    Biochemical purification showed Ser189 is phosphorylated by a specific cellular kinase distinct from MEK1/2, indicating ERK3 uses a non-canonical activation route.

    Evidence Biochemical purification, in vitro kinase assay, PP2A treatment, ERK3/ERK2 chimeras

    PMID:8662649

    Open questions at the time
    • The kinase was not molecularly identified here
    • Physiological signals controlling this activity unknown at the time
  3. 2001 Medium

    Domain-swap experiments localized the determinant of ERK3's MEK-independent constitutive nuclear localization to its catalytic-domain half, explaining its divergence from ERK2.

    Evidence ERK2/ERK3 chimeric constructs with localization and MEK1 interaction readouts

    PMID:11741894

    Open questions at the time
    • Specific export/import signals not mapped here
    • Single lab
  4. 2003 High

    Defining CRM1-dependent export established that ERK3 shuttling, not static localization, governs its cell-cycle effects.

    Evidence Leptomycin B, CRM1 overexpression, GST pulldown, cell cycle analysis

    PMID:12915405

    Open questions at the time
    • Mechanism linking shuttling to cell cycle arrest not resolved
    • Direct nuclear export signal not mapped
  5. 2004 High

    Identification of MK5/PRAK as the direct ERK3 partner and substrate defined the core effector axis and revealed mutual protein stabilization.

    Evidence Reciprocal Co-IP, in vitro kinase assay, siRNA, ERK3-/- fibroblasts, MK5 KO mice (two companion papers)

    PMID:15538386 PMID:15577943

    Open questions at the time
    • Physiological downstream substrates of activated MK5 not yet defined
    • Whether MK5 activation is strictly kinase-dependent vs scaffolding was contested between studies
  6. 2008 High

    Showing that activation-loop phosphorylation drives stable ERK3–MK5 complex formation and cytoplasmic redistribution linked Ser189 status to effector engagement.

    Evidence Phospho-specific antibodies, in vitro kinase assay, MK5 interaction and fractionation assays

    PMID:18720373

    Open questions at the time
    • Did not identify the upstream kinase
    • Quantitative stoichiometry of the complex not determined
  7. 2009 High

    Defining the FRIEDE docking motif explained how ERK3/ERK4 recruit MK5 through a non-canonical mechanism independent of the canonical CD domain.

    Evidence Peptide overlay, FRIEDE mutagenesis, Co-IP, MK5 translocation assays

    PMID:19473979

    Open questions at the time
    • Structural basis of FRIEDE–MK5 contact not solved here
    • Whether other partners use this motif unknown
  8. 2010 High

    Identifying group I PAKs as the Ser189 kinase placed ERK3 downstream of Rac1, completing a PAK–ERK3–MK5 pathway.

    Evidence Biochemical purification, in vitro kinase assay, RNAi of PAK1/2/3, phospho-specific antibodies, activated Rac1

    PMID:21177870 PMID:21317288

    Open questions at the time
    • Upstream receptors/signals engaging Rac1-PAK toward ERK3 in physiological contexts not fully mapped
    • Whether other kinases contribute to Ser189 in vivo
  9. 2010 High

    Cdk1-mediated C-terminal phosphorylation, reversed by Cdc14 phosphatases, was shown to stabilize ERK3 during mitosis, revealing cell-cycle control of ERK3 abundance.

    Evidence In vitro kinase assay with cyclin B-Cdk1, MS phosphosite mapping, Cdc14 binding, pulse-chase, mutagenesis

    PMID:18235225 PMID:20236090

    Open questions at the time
    • Functional consequence of mitotic ERK3 stabilization on substrates unclear
    • Cdc14 in vivo relevance limited
  10. 2012 High

    Discovery of SRC-3/Ser857 as a direct substrate connected ERK3 to a transcriptional program promoting invasion, extending its role beyond the MK5 axis.

    Evidence Co-IP, in vitro kinase assay, S857A mutagenesis, knockdown, xenograft, MMP assays

    PMID:22505454

    Open questions at the time
    • Whether SRC-3 phosphorylation occurs in non-cancer contexts unknown
    • Relative contribution vs MK5 axis not quantified
  11. 2012 High

    Extending the ERK3/MK5 module to septin7 and neuronal targets linked it to cytoskeletal and dendritic spine development.

    Evidence Interaction screens, Co-IP, in vitro kinase assay, MK5 KO mice, primary neuron transfection

    PMID:22508986

    Open questions at the time
    • Direct ERK3 substrate among these targets vs MK5-mediated effects not fully separated
    • In vivo ERK3-specific neuronal phenotype not tested
  12. 2017 High

    Identifying DUSP2 as a direct phosphatase that dephosphorylates the ERK3/ERK4 activation loop established negative regulation of the pathway.

    Evidence Co-IP, in vitro phosphatase assay, domain mapping, MK5 activation and DUSP2 stabilization assays

    PMID:28252035

    Open questions at the time
    • Physiological signals inducing DUSP2 toward ERK3 not defined
    • Single study
  13. 2018 High

    Demonstrating Ser189-dependence of ERK3 activity toward SRC-3, alongside residual kinase-independent invasion, revealed dual mechanisms underlying ERK3-driven invasiveness.

    Evidence In vitro kinase assays with S189A and kinase-dead mutants, migration/invasion and MMP assays

    PMID:30166347

    Open questions at the time
    • Molecular basis of the kinase-independent component undefined
    • Single lab
  14. 2022 High

    Linking the ERK3/MK5 module to FoxO3 phosphorylation in muscle and to FOXO1/ATGL in adipocytes mapped tissue-level physiological outputs of the pathway.

    Evidence Mapk6KD/KD and MK5 KO mice, adipocyte-specific ERK3 KO, in vitro kinase assay, lipolysis and differentiation assays

    PMID:32139423 PMID:35141958

    Open questions at the time
    • Whether FoxO3/FOXO1 are direct ERK3 vs MK5 substrates fully delineated
    • Crosstalk between metabolic and myogenic outputs untested
  15. 2022 High

    Identification of supervillin/Ser245 as a direct substrate connected ERK3 kinase activity to cytokinesis completion and ploidy control.

    Evidence Phosphoproteomics, in vitro kinase assay, S245A mutagenesis rescue, cytokinesis/multinucleation assays

    PMID:36576983

    Open questions at the time
    • Upstream signals timing ERK3 activity to cytokinesis unknown
    • In vivo relevance of multinucleation phenotype untested
  16. 2022 Medium

    Defining FBXW7-mediated proteasomal degradation and EGLN3-regulated chaperone-mediated autophagy established that ERK3 abundance is controlled by parallel degradative routes.

    Evidence Two-hybrid, Co-IP, ubiquitination assays, T417A/T421A mutagenesis, CMA-component Co-IP, EGLN3 knock-in mice

    PMID:35022544 PMID:35124697

    Open questions at the time
    • Relative flux through proteasome vs CMA in different cell states unclear
    • Signals selecting one route over the other undefined
  17. 2023 High

    Showing ERK3 acts as a CDC42 GEF and phosphorylates ARP3/Ser418 directly coupled ERK3 to actin nucleation and filopodia formation, broadening its catalytic repertoire.

    Evidence In vitro GEF assay, ARP3 in vitro kinase assay, actin polymerization with purified ARP2/3, ERK3 depletion phenotypes

    PMID:37057894

    Open questions at the time
    • Structural basis for GEF activity in a kinase fold undefined
    • Single lab
  18. 2025 Medium

    Demonstrating intracellular pH-dependent control of ERK3 half-life via C-terminal pH-sensing motifs added a metabolic/microenvironmental layer to ERK3 stability regulation.

    Evidence Intracellular pH manipulation, half-life measurements, quantitative proteomics, C-terminus mutants

    PMID:41123996

    Open questions at the time
    • Molecular identity of pH-sensing residues only partially defined
    • Connection to the FBXW7/CMA degradation machinery not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the multiple direct substrates (MK5, SRC-3, ARP3, supervillin, AKT, TDP2) and the kinase-independent functions are coordinated, and what receptor-proximal signals select among ERK3's degradative versus stabilizing pathways, remains unresolved.
  • No unifying model integrating direct substrates with the MK5 scaffold axis
  • Physiological triggers gating ERK3 stability vs degradation undefined
  • Kinase-independent mechanisms remain mechanistically opaque

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:0008092 cytoskeletal protein binding 2 GO:0140657 ATP-dependent activity 2 GO:0098772 molecular function regulator activity 1
Localization
GO:0005634 nucleus 3 GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2 GO:0005886 plasma membrane 2
Pathway
R-HSA-162582 Signal Transduction 3 R-HSA-1640170 Cell Cycle 3 R-HSA-1643685 Disease 3 R-HSA-392499 Metabolism of proteins 3
Partners
CRM1DUSP2FBXW7MK5PAK1PAK2SRC-3TRIM21
Complex memberships
ERK3/MK5/septin7 ternary complexERK3–MK5 complex

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2004 ERK3 specifically interacts with and phosphorylates MAPK-activated protein kinase 5 (MK5/PRAK), activating it both in vitro and in vivo. This interaction causes nuclear exclusion of both ERK3 and MK5. Endogenous MK5 activity is reduced by siRNA-mediated knockdown of ERK3 and in ERK3-/- mouse fibroblasts. Reciprocally, MK5 depletion causes dramatic reduction in endogenous ERK3 levels, suggesting MK5 acts as a chaperone for ERK3. Co-immunoprecipitation, in vitro kinase assay, siRNA knockdown, ERK3-/- mouse fibroblasts, PC12 cell differentiation model The EMBO journal High 15577943
2004 ERK3 specifically interacts with MK5 in vitro and in vivo; ERK3 expression drives nuclear-cytoplasmic translocation and activation of MK5. Activation of MK5 is independent of ERK3 enzymatic activity but depends on MK5's own catalytic activity and a region in ERK3's C-terminal extension. Deletion of MK5 leads to strong reduction of ERK3 protein levels. Co-immunoprecipitation, mammalian cell expression, kinase-dead ERK3 mutants, MK5 knockout mice The EMBO journal High 15538386
1996 ERK3 is constitutively localized in the nucleus in exponentially growing, quiescent, and growth factor-stimulated cells; the C-terminal 180 aa are not required for nuclear localization. Recombinant ERK3 autophosphorylates on Ser189 in vitro and in vivo; mutation of conserved catalytic Asp171 eliminates autophosphorylation. ERK3 does not phosphorylate typical MAP kinase substrates (myelin basic protein, etc.). Immunoblotting, subcellular fractionation, immunofluorescence, in vitro kinase assay, site-directed mutagenesis (D171A, S189) The Journal of biological chemistry High 8621539
2003 ERK3 undergoes CRM1-dependent nuclear export; treatment with leptomycin B causes nuclear accumulation, and ectopic CRM1 promotes cytoplasmic relocalization. CRM1 binds ERK3 in vitro. Forced nuclear or cytoplasmic localization of ERK3 attenuates its ability to induce cell cycle arrest in fibroblasts, indicating nucleocytoplasmic shuttling is required for its negative effect on cell cycle progression. Leptomycin B treatment, CRM1 overexpression, snurportin-1 overexpression, GST pulldown (CRM1 binds ERK3 in vitro), cell cycle analysis The Journal of biological chemistry High 12915405
2008 ERK3 (and ERK4) are phosphorylated on activation loop Ser189 in vivo by an upstream cellular kinase, detectable in resting cells. Activation loop phosphorylation stimulates intrinsic catalytic activity of ERK3 and is required for formation of stable active complexes with MK5, and for efficient cytoplasmic redistribution of ERK3/MK5 complexes. Phospho-specific antibodies, in vitro kinase assay, MK5 interaction assays, subcellular fractionation Journal of cellular physiology High 18720373
2010 Group I p21-activated kinases (PAK1/2/3) phosphorylate ERK3 on activation loop Ser189 (and ERK4 on Ser186) both in vitro and in vivo. Activated Rac1 augments this phosphorylation; siRNA silencing of PAK1/2/3 abolishes Rac1-induced ERK3 Ser189 phosphorylation. PAK-mediated phosphorylation results in enzymatic activation of ERK3 and downstream activation of MK5, defining a PAK-ERK3-MK5 signaling pathway. Biochemical kinase purification, in vitro kinase assay, RNAi, phospho-specific antibodies, activated Rac1 expression The Journal of biological chemistry High 21177870
2011 Recombinant PAK2 directly phosphorylates ERK3 at Ser189 in vitro (confirmed by protein microarray and solution-based kinase assay). Selective inhibition of class I PAK kinase activity in cells increases nuclear accumulation of ERK3, reduces Ser189 phosphorylation, and inhibits ERK3-PRAK complex formation. Protein microarray, in vitro kinase assay, phospho-specific antisera, PAK inhibitor treatment, nuclear/cytoplasmic fractionation The Journal of biological chemistry High 21317288
2009 ERK3 and ERK4 interact with MK5 through a novel FRIEDE motif in the L16 extension C-terminal to the CD domain; a single I→K substitution in FRIEDE completely abolishes binding, activation, and translocation of MK5 by both ERK3 and ERK4. The canonical CD domain is dispensable for this interaction. Activation loop phosphorylation of ERK3/ERK4 is required for MK5 binding, suggesting a phosphorylation-dependent switch mechanism. Peptide overlay assays, site-directed mutagenesis (FRIEDE motif), Co-immunoprecipitation, MK5 translocation assays The Journal of biological chemistry High 19473979
1996 A novel nuclear/cytosolic protein kinase activity phosphorylates ERK3 at a single site, Ser189, and is distinct from MEK1/2. This kinase is inactivated by PP2A and does not phosphorylate ERK2 or ERK2 mutants bearing the ERK3 phospho-acceptor sequence, indicating high specificity for ERK3. Biochemical purification, in vitro kinase assay, PP2A treatment, ERK3/ERK2 chimeric mutants The Journal of biological chemistry High 8662649
2012 ERK3 interacts with and phosphorylates SRC-3 (steroid receptor coactivator 3) at Ser857. This phosphorylation is essential for SRC-3 interaction with PEA3 transcription factor, which promotes MMP gene expression and proinvasive activity in lung cancer cells. Knockdown of ERK3 inhibits lung cancer cell invasion and tumor formation in xenograft mouse models. Co-immunoprecipitation, in vitro kinase assay, site-directed mutagenesis (S857A), gene knockdown, xenograft mouse model, MMP expression assays The Journal of clinical investigation High 22505454
2012 The ERK3/MK5 signaling complex interacts with septin7 (Sept7) to form a ternary complex that can phosphorylate Borg proteins (regulators of Sept7). MK5 also interacts with and phosphorylates kalirin-7 (Kal7) in neurons. The ERK3/MK5 module stimulates Sept7-dependent dendrite development and spine formation in transfected primary neurons; MK5-deficient mice show impaired dendritic spine formation in hippocampal neurons. Large-scale interaction screens, Co-immunoprecipitation, in vitro kinase assay, MK5 knockout mice, primary neuron transfection Molecular and cellular biology High 22508986
2017 DUSP2 (an inducible nuclear dual-specificity MAP kinase phosphatase) binds to ERK3 and ERK4 via the ERK3/ERK4 CD domain interacting with the DUSP2 KIM motif. This interaction is direct and results in dephosphorylation of ERK3/ERK4 activation loop, stabilization of DUSP2, and inhibition of MK5 activation downstream. Co-immunoprecipitation, in vitro phosphatase assay, domain mapping, MK5 activation assays, DUSP2 stabilization experiments Scientific reports High 28252035
2010 ERK3 is stoichiometrically hyperphosphorylated during mitotic entry and dephosphorylated at M→G1 transition. Cyclin B-Cdk1 phosphorylates four C-terminal ERK3 sites (Ser684, Ser688, Thr698, Ser705) in vitro and in vivo. Cdc14A and Cdc14B phosphatases bind ERK3 and reverse its C-terminal phosphorylation. Alanine substitution of the four phosphorylation sites markedly decreases ERK3 half-life in mitosis, linking Cdk1-mediated phosphorylation to ERK3 stabilization. In vitro kinase assay with purified cyclin B-Cdk1, mass spectrometry phosphosite identification, Cdc14 binding assay, protein half-life measurements (pulse-chase), site-directed mutagenesis The Biochemical journal High 20236090
2007 Human Cdc14A phosphatase interacts with ERK3 directly via ERK3's C-terminal domain (GST pulldown). Cdc14A can remove Cdk-mediated phosphorylation of ERK3 in vitro. Cdc14A forms a stable complex with ERK3 in human cells independent of phosphatase activity. Cdc14A upregulation leads to redistribution of ERK3 substrate MK5 from nucleus to cytoplasm and stabilizes the ERK3/cyclin D3 complex. Yeast two-hybrid screen, GST pulldown, Co-immunoprecipitation, in vitro phosphatase assay, subcellular localization analysis Cell cycle (Georgetown, Tex.) Medium 18235225
2016 ERK3 phosphorylates tyrosyl-DNA phosphodiesterase 2 (TDP2) at Ser60 and regulates TDP2's phosphodiesterase activity, thereby protecting lung cancer cells against Topoisomerase 2 inhibitor-induced DNA damage and growth inhibition. In vitro kinase assay, site-directed mutagenesis (S60), TDP2 phosphodiesterase activity assay, cell viability assays with Top2 inhibitors Oncotarget Medium 26701725
2020 β-adrenergic stimulation stabilizes ERK3, leading to formation of an ERK3/MK5 complex that drives lipolysis in adipocytes. The ERK3/MK5 pathway promotes expression of the lipolytic enzyme ATGL via the transcription factor FOXO1. Targeted deletion of ERK3 in mouse adipocytes inhibits lipolysis, elevates energy dissipation, and promotes a lean phenotype with improved diabetes markers. High-throughput screen, co-immunoprecipitation, adipocyte-specific ERK3 knockout mice, lipolysis assays, FOXO1 and ATGL expression analysis Genes & development High 32139423
2021 MAPK6 directly activates AKT by phosphorylating AKT at Ser473 independent of mTORC2. MAPK6 interacts with AKT through its C34 region and C-terminal tail. Inhibiting MAPK6 sensitizes cancer cells to mTOR kinase inhibitors. Co-immunoprecipitation (domain mapping), in vitro kinase assay (AKT phosphorylation at S473), mTOR inhibitor combination studies, cancer cell proliferation assays Science advances Medium 34767444
2020 ERK3 is necessary for production of interleukin-8 (IL-8) and is critical for AP-1 signaling through its interaction with and regulation of c-Jun protein. The secretome of ERK3-deficient cells is defective in chemotaxis of neutrophils and monocytes in vitro and in vivo. 3D organoid system, ERK3 knockdown/knockout, secretome analysis, chemotaxis assays (in vitro and in vivo), c-Jun interaction/regulation experiments eLife Medium 32314963
2023 ERK3 directly acts as a guanine nucleotide exchange factor for CDC42 and phosphorylates ARP3 (subunit of ARP2/3 complex) at Ser418 to promote actin polymerization and filopodia formation. ERK3 protein bound directly to the purified ARP2/3 complex and augmented polymerization of actin in vitro. Depletion of ERK3 prevented CDC42/RAC1 activation, F-actin maintenance, filopodia formation, and epithelial cell migration. In vitro GEF assay (CDC42 nucleotide exchange), in vitro kinase assay (ARP3 phosphorylation at S418), in vitro actin polymerization assay with purified ARP2/3, ERK3 depletion with defined cytoskeletal phenotypes eLife High 37057894
2022 FBXW7 acts as an E3 ubiquitin ligase for ERK3, targeting it for ubiquitination-mediated proteasomal degradation. ERK3 binds FBXW7 through its C34D region, specifically at Thr417 and Thr421, which interact with the WD40 domain of FBXW7. T417A/T421A double mutation abrogates FBXW7-mediated ubiquitination. FBXW7 depletion restores ERK3 protein levels. Mammalian two-hybrid assay, co-immunoprecipitation, ubiquitination assay, proteasome inhibitor treatment, site-directed mutagenesis (T417A/T421A) Experimental & molecular medicine High 35022544
2022 EGLN3 catalyzes hydroxylation of ERK3, and this hydroxylation antagonizes chaperone-mediated autophagy (CMA)-mediated degradation of ERK3 by reducing ERK3 interaction with LAMP2A. ERK3 interacts with HSC70 and LAMP2A (core CMA components) and is degraded by the CMA-lysosome pathway; EGLN3-mediated hydroxylation blocks this. Co-immunoprecipitation (ERK3-HSC70 and ERK3-LAMP2A), hydroxylation assay, CMA-lysosome pathway assays, EGLN3 catalytically inactive knock-in mice Oncogene Medium 35124697
2022 ERK3 and MK5 act in a linear pathway to control postnatal myogenic differentiation: ERK3 kinase-inactive mice (Mapk6KD/KD) have impaired skeletal muscle growth and regeneration. MK5 directly phosphorylates FoxO3, promoting its degradation and reducing FoxO3 association with MyoD. FoxO3 depletion partially rescues premature differentiation caused by ERK3/MK5 inactivation. Mapk6KD/KD (kinase-dead knock-in) mice, MK5 KO mice, C2C12/primary myoblast differentiation assays, MK5 in vitro kinase assay (FoxO3 phosphorylation), MK5 inhibitor, FoxO3 rescue experiments Journal of cellular physiology High 35141958
2022 Supervillin (SVIL) is a direct ERK3 substrate; ERK3 phosphorylates SVIL at Ser245 to regulate myosin II activation and cytokinesis completion. Depletion of SVIL or ERK3 leads to increased cytokinesis failure and multinucleation, a phenotype rescued by wild-type SVIL but not by non-phosphorylatable S245A mutant. Quantitative phosphoproteomics, in vitro kinase assay, site-directed mutagenesis (S245A), siRNA knockdown, cytokinesis and multinucleation assays Journal of cellular physiology High 36576983
2001 The C-terminal halves of ERK2 and ERK3 (catalytic domain) are primarily responsible for their distinct subcellular localizations in resting cells. The N-terminal folding domain of ERK2 is required for its activation by MEK1, interaction with MEK1, and nuclear accumulation; swapping in the ERK3 N-terminal domain abrogates these. ERK3 is thus constitutively nuclear through a mechanism residing in its C-terminal catalytic domain half, independent of MEK. ERK2/ERK3 chimeric protein constructs, subcellular localization assays, MEK1 interaction assays The Journal of biological chemistry Medium 11741894
2001 ERK3 expression is upregulated at the mRNA and protein level by proteasome inhibitors in a p38 pathway-dependent manner. p38 pathway kinase inhibitors prevent proteasome-dependent ERK3 induction. ERK3 upregulation is independent of p53, Bcl2, and caspase-3. Ectopic ERK3 expression increases cellular resistance to proteasome inhibition. Proteasome inhibitor treatment (peptide-based inhibitors, lactacystin), p38 inhibitors, Western blot, ERK3 ectopic expression, cell viability assays The Journal of biological chemistry Medium 11148204
1996 ERK3 activity is constitutively activated (~10-fold increase) in colon cancer cells stably transfected with PKC-beta1 or PKC-beta2, without a change in ERK3 protein level. TPA-induced downregulation of PKC activity reduces ERK3 activity, establishing a causal link. Activated ERK3 is found in nuclear and membrane fractions in PKC-beta transfectants. Stable transfection, immune complex kinase assay, in-gel kinase assay, TPA-mediated PKC downregulation, subcellular fractionation The Journal of biological chemistry Medium 8626698
2006 ERK3/MAPK6 expression is upregulated by BRAF(V600E) signaling via MEK1/2; pharmacological inhibition of BRAF or MEK1/2, or RNAi-mediated BRAF knockdown, leads to rapid ERK3 protein degradation in melanoma cells. Conditional BRAF(V600E) expression system, MEK inhibitors, BRAF RNAi, Western blot, microarray International journal of oncology Medium 16964379
2006 ERK3 associates with microtubule-associated protein MAP2 in pancreatic beta cells; PMA-induced ERK3 phosphorylation is accompanied by increased ERK3/MAP2 association and MAP2 phosphorylation. Antisense oligonucleotide-mediated ERK3 knockdown abolishes glucose-stimulated insulin secretion and PMA-induced insulin secretion, indicating ERK3 is required for stimulus-secretion coupling in beta cells. Co-immunoprecipitation (ERK3-MAP2), antisense oligonucleotide knockdown, insulin secretion assays, immunohistochemistry (beta cell-specific expression) Molecular and cellular endocrinology Medium 16597486
2010 ERK3 localizes to spindle fibers and asters in mouse oocytes during meiosis I–II. Deletion of ERK3 by morpholino injection causes oocyte arrest at MI with impaired spindles, misaligned chromosomes, persistent BubR1 on kinetochores, disrupted kinetochore-microtubule attachments, and failure of homologous chromosome segregation. ERK3 morpholino microinjection in mouse oocytes, immunofluorescence (spindle localization, BubR1, α-tubulin), chromosome spreading, low-temperature kinetochore-MT stability assay PloS one Medium 20927325
2014 ERK3 promotes endothelial cell migration, proliferation, and tube formation by upregulating SRC-3/SP1-mediated VEGFR2 expression. The mechanism involves ERK3-stimulated formation of a transcriptional complex containing SRC-3, SP-1, and CBP. ERK3 gene expression is upregulated by cytokines through c-Jun binding to the ERK3 gene promoter. Co-immunoprecipitation (SRC-3/SP-1/CBP complex), VEGFR2 promoter reporter assays, ERK3 knockdown, endothelial migration/proliferation/tube formation assays Journal of cellular physiology Medium 24585635
2018 Activation loop phosphorylation (Ser189) is important for ERK3 kinase activity toward SRC-3: S189A mutation greatly decreases ERK3 kinase activity toward SRC-3 and reduces the ability to promote lung cancer cell migration, invasion, and MMP expression. A kinase-inactive ERK3 mutant still promotes invasion to a lesser extent, indicating both kinase-dependent and kinase-independent mechanisms contribute to ERK3-driven invasiveness. In vitro kinase assay (S189A and kinase-dead mutants vs. SRC-3 substrate), lung cancer cell migration/invasion assays, MMP expression analysis The Journal of biological chemistry High 30166347
2025 Intracellular acidification markedly increases ERK3 half-life, while alkalinization accelerates its degradation. This pH-dependent regulation is rapid, reversible, and cell-type consistent. A region in ERK3's C-terminus contains pH-sensing motifs responsible for this regulation. Intracellular pH manipulation, protein half-life measurements, quantitative proteomics, C-terminus deletion/mutant analysis Proceedings of the National Academy of Sciences of the United States of America Medium 41123996
2023 ERK3 interacts with DGKζ (diacylglycerol kinase ζ) via its C34 domain; DGKζ binds to the N-terminal and C1 domains of ERK3. Co-overexpression of DGKζ and ERK3 completely blocks ERK3-promoted lung cancer cell migration; DGKζ requires the C34 domain of ERK3 to prevent ERK3-mediated migration. Yeast two-hybrid, co-immunoprecipitation, in vitro binding assay, co-localization, ERK3 domain deletion mutants, lung cancer cell migration assays Frontiers in cell and developmental biology Medium 37287450
2020 ERK3 L290P/V cancer mutations enhance ERK3's cytoplasmic localization by increasing interaction with the nuclear export factor CRM1, thereby increasing migration/invasion-promoting capability without clear effects on intrinsic kinase activity. Site-directed mutagenesis (L290P, L290V), CRM1 co-immunoprecipitation, subcellular fractionation, migration/invasion assays Scientific reports Medium 29101390
2023 ERK3 interacts with Snail and enhances Snail protein stability by inhibiting the binding of FBXO11 (an E3 ubiquitin ligase) to Snail, thereby preventing Snail ubiquitination and degradation. ERK3 does not directly phosphorylate Snail. Co-immunoprecipitation, ubiquitination assay, protein stability assay, negative result for direct phosphorylation Cancers Medium 38201533
2025 TRIM21 (ubiquitin ligase) binds MAPK6 and promotes its ubiquitin-proteasome degradation in endothelial cells exposed to disturbed shear stress. Endothelial MAPK6 regulates inflammation via the EGR1/CXCL12 axis; endothelium-specific MAPK6 knockout increases plaque area in ApoE-/- mice, reversible by CXCL12 neutralization. Co-immunoprecipitation (TRIM21-MAPK6), RNA-seq, proteomic analysis, endothelium-specific Mapk6 knockout mice, AAV-MAPK6 overexpression, CXCL12 neutralization rescue Clinical and translational medicine Medium 39763069
2015 ERK3 localizes to the cell periphery of breast cancer cells during adhesion to collagen I. ERK3 overexpression reduces cell spread area and increases migration speed. Importantly, a kinase-inactive ERK3 mutant phenocopies wild-type ERK3 overexpression in reducing spread area and increasing migration, revealing a kinase-independent function. Live cell imaging, ERK3 overexpression (WT and kinase-dead), siRNA knockdown, morphological analysis during cell adhesion Cell adhesion & migration Medium 26588708
2020 The C-terminus tail of ERK3 is required for full kinase activity toward SRC-3 and for ERK3-promoted cancer cell migration/invasion. Septin 7, which interacts with ERK3 via its C-terminus tail, acts as a downstream effector for ERK3-induced cancer cell migration. C-terminus deletion mutants, in vitro kinase assay (SRC-3 substrate), septin 7 knockdown, migration/invasion assays International journal of molecular sciences Medium 32516969
1996 ERK3 specifically co-elutes with B-Raf (but not c-Raf1) after anion exchange chromatography of rat hippocampal lysates; ERK3 is released from B-Raf immunoprecipitates upon ATP incubation, suggesting a specific association of ERK3 with B-Raf in rat hippocampus. Anion exchange chromatography, co-immunoprecipitation, ATP-dependent dissociation assay Biochemical and biophysical research communications Low 8954940
2014 ERK3 expression is induced in CD4+ and CD8+ T cells following TCR stimulation, requiring ERK1/2 activation. ERK3 protein is phosphorylated and associates with MK5 in activated primary T cells. ERK3-deficient T cells show decreased proliferation and impaired cytokine secretion following stimulation with low-dose anti-CD3. ERK3-/- mice, T cell activation assays, ERK1/2 inhibitor treatment, co-immunoprecipitation (ERK3-MK5 in activated T cells), cytokine measurement PloS one Medium 24475167
2018 ERK3 regulates epithelial architecture in Xenopus embryos and human breast epithelial cells: ERK3 knockdown impairs adherens and tight-junction protein distribution and tight-junction barrier function. ERK3 is required for full activation of TFAP2A (AP-2α)-dependent transcription, and TFAP2A knockdown phenocopies ERK3 knockdown. Xenopus ERK3 knockdown (morpholino), human epithelial cell ERK3 KD, microarray gene expression, tight-junction barrier assay, TFAP2A luciferase reporter The Journal of biological chemistry Medium 29674317
2020 Crystal structure of the ERK3 kinase domain was determined, revealing a distinct ATP binding pocket compared to ERK2, particularly in the A-loop, GC-loop, and αC-helix conformations. The structure also indicates a potential structural link toward MK5 interaction via the FHIEDE motif. X-ray crystallography (ERK3 kinase domain), small molecule inhibitor screening with biochemical and cellular assays (NanoBRET) Bioorganic & medicinal chemistry letters Medium 32927028
2020 Crystal structure of the ERK3 kinase domain was determined providing molecular insights into its distinct ATP binding pocket relative to ERK2, explaining differences in inhibitor binding properties. X-ray crystallography (ERK3 kinase domain and CLK1 in complex with inhibitor CAF052), medium-scale small molecule screening International journal of molecular sciences Medium 33114754
2024 ERK3 is expressed in atrial and ventricular cardiac fibroblasts (not myocytes). ERK3 co-immunoprecipitates with MK5 in heart lysates. ERK3 haploinsufficiency reduces cardiac hypertrophy and Col1a1 mRNA increase after transverse aortic constriction. ERK3 knockdown reduces TGF-β-induced collagen expression and impairs myofibroblast motility. Co-immunoprecipitation (heart lysates), ERK3+/- mice with TAC model, siRNA knockdown in primary cardiac fibroblasts, collagen assays, motility assays Physiological reports Medium 38872461

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2004 Activation of MK5/PRAK by the atypical MAP kinase ERK3 defines a novel signal transduction pathway. The EMBO journal 115 15577943
2012 ERK3 signals through SRC-3 coactivator to promote human lung cancer cell invasion. The Journal of clinical investigation 106 22505454
2004 Scaffolding by ERK3 regulates MK5 in development. The EMBO journal 102 15538386
1996 ERK3 is a constitutively nuclear protein kinase. The Journal of biological chemistry 86 8621539
2019 MicroRNA-374a protects against myocardial ischemia-reperfusion injury in mice by targeting the MAPK6 pathway. Life sciences 73 31265855
2018 NEAT1/hsa-mir-98-5p/MAPK6 axis is involved in non-small-cell lung cancer development. Journal of cellular biochemistry 69 29095526
2003 Nuclear export of ERK3 by a CRM1-dependent mechanism regulates its inhibitory action on cell cycle progression. The Journal of biological chemistry 68 12915405
2008 Activation loop phosphorylation of the atypical MAP kinases ERK3 and ERK4 is required for binding, activation and cytoplasmic relocalization of MK5. Journal of cellular physiology 64 18720373
2017 Metformin potentiates the effect of arsenic trioxide suppressing intrahepatic cholangiocarcinoma: roles of p38 MAPK, ERK3, and mTORC1. Journal of hematology & oncology 61 28241849
1994 Cloning and characterization of p97MAPK, a novel human homolog of rat ERK-3. Molecular and cellular biology 61 7969157
2009 Loss of Erk3 function in mice leads to intrauterine growth restriction, pulmonary immaturity, and neonatal lethality. Proceedings of the National Academy of Sciences of the United States of America 59 19805361
2010 Activation loop phosphorylation of ERK3/ERK4 by group I p21-activated kinases (PAKs) defines a novel PAK-ERK3/4-MAPK-activated protein kinase 5 signaling pathway. The Journal of biological chemistry 58 21177870
2018 Long non-coding RNA SNHG6 enhances cell proliferation, migration and invasion by regulating miR-26a-5p/MAPK6 in breast cancer. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 57 30522015
2018 Effects of miR-26a-5p on neuropathic pain development by targeting MAPK6 in in CCI rat models. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 56 30118880
2012 The extracellular signal-regulated kinase 3 (mitogen-activated protein kinase 6 [MAPK6])-MAPK-activated protein kinase 5 signaling complex regulates septin function and dendrite morphology. Molecular and cellular biology 55 22508986
2011 Identification of the atypical MAPK Erk3 as a novel substrate for p21-activated kinase (Pak) activity. The Journal of biological chemistry 54 21317288
2015 A novel role for atypical MAPK kinase ERK3 in regulating breast cancer cell morphology and migration. Cell adhesion & migration 51 26588708
1996 Characterization of a protein kinase that phosphorylates serine 189 of the mitogen-activated protein kinase homolog ERK3. The Journal of biological chemistry 42 8662649
2019 MiR-144-3p: a novel tumor suppressor targeting MAPK6 in cervical cancer. Journal of physiology and biochemistry 41 31016619
2017 MicroRNA-26a targets MAPK6 to inhibit smooth muscle cell proliferation and vein graft neointimal hyperplasia. Scientific reports 40 28429763
2017 Propofol protects against hepatic ischemia/reperfusion injury via miR-133a-5p regulating the expression of MAPK6. Cell biology international 39 28198596
1996 Increased expression of protein kinase C beta activates ERK3. The Journal of biological chemistry 38 8626698
2009 Docking of PRAK/MK5 to the atypical MAPKs ERK3 and ERK4 defines a novel MAPK interaction motif. The Journal of biological chemistry 37 19473979
2007 A functional link between the human cell cycle-regulatory phosphatase Cdc14A and the atypical mitogen-activated kinase Erk3. Cell cycle (Georgetown, Tex.) 36 18235225
2020 ERK3/MAPK6 controls IL-8 production and chemotaxis. eLife 35 32314963
2019 Long noncoding RNA NEAT1 sponges miR-495-3p to enhance myocardial ischemia-reperfusion injury via MAPK6 activation. Journal of cellular physiology 35 31347173
2014 ERK3 promotes endothelial cell functions by upregulating SRC-3/SP1-mediated VEGFR2 expression. Journal of cellular physiology 32 24585635
2016 ERK3 regulates TDP2-mediated DNA damage response and chemoresistance in lung cancer cells. Oncotarget 31 26701725
2001 Proteasome- and p38-dependent regulation of ERK3 expression. The Journal of biological chemistry 31 11148204
2022 Inactivation of EGLN3 hydroxylase facilitates Erk3 degradation via autophagy and impedes lung cancer growth. Oncogene 30 35124697
2020 The adrenergic-induced ERK3 pathway drives lipolysis and suppresses energy dissipation. Genes & development 29 32139423
2012 Tumour promoting and suppressing roles of the atypical MAP kinase signalling pathway ERK3/4-MK5. Journal of molecular signaling 29 22800433
2021 MAPK6-AKT signaling promotes tumor growth and resistance to mTOR kinase blockade. Science advances 28 34767444
2017 Regulation of atypical MAP kinases ERK3 and ERK4 by the phosphatase DUSP2. Scientific reports 26 28252035
2010 C-terminal domain phosphorylation of ERK3 controlled by Cdk1 and Cdc14 regulates its stability in mitosis. The Biochemical journal 26 20236090
2023 CircDNAJC11 interacts with TAF15 to promote breast cancer progression via enhancing MAPK6 expression and activating the MAPK signaling pathway. Journal of translational medicine 25 36895010
2023 ERK3/MAPK6 dictates CDC42/RAC1 activity and ARP2/3-dependent actin polymerization. eLife 25 37057894
2022 Rab31 promotes the invasion and metastasis of cervical cancer cells by inhibiting MAPK6 degradation. International journal of biological sciences 25 34975321
2017 A regulatory BMI1/let-7i/ERK3 pathway controls the motility of head and neck cancer cells. Molecular oncology 25 28079973
2022 Exosomes from miR-374a-5p-modified mesenchymal stem cells inhibit the progression of renal fibrosis by regulating MAPK6/MK5/YAP axis. Bioengineered 24 35137672
1996 Primary structure, expression and chromosomal locus of a human homolog of rat ERK3. Oncogene 24 8875998
2018 Activation loop phosphorylation of ERK3 is important for its kinase activity and ability to promote lung cancer cell invasiveness. The Journal of biological chemistry 23 30166347
2010 Targeted inactivation of Mapk4 in mice reveals specific nonredundant functions of Erk3/Erk4 subfamily mitogen-activated protein kinases. Molecular and cellular biology 23 20956558
2006 Regulation of ERK3/MAPK6 expression by BRAF. International journal of oncology 22 16964379
2022 FBXW7-mediated ERK3 degradation regulates the proliferation of lung cancer cells. Experimental & molecular medicine 21 35022544
2014 Up-regulated microRNA499a by hepatitis B virus induced hepatocellular carcinogenesis via targeting MAPK6. PloS one 21 25340781
2010 ERK3 is required for metaphase-anaphase transition in mouse oocyte meiosis. PloS one 21 20927325
2006 ERK3 associates with MAP2 and is involved in glucose-induced insulin secretion. Molecular and cellular endocrinology 21 16597486
2022 LncRNA LINC00649 recruits TAF15 and enhances MAPK6 expression to promote the development of lung squamous cell carcinoma via activating MAPK signaling pathway. Cancer gene therapy 18 35228660
2021 miR‑653‑5p suppresses the growth and migration of breast cancer cells by targeting MAPK6. Molecular medicine reports 18 33495824
2014 The non-classical MAP kinase ERK3 controls T cell activation. PloS one 18 24475167
2018 miR-98 inhibits cell proliferation and induces cell apoptosis by targeting MAPK6 in HUVECs. Experimental and therapeutic medicine 17 29456679
2002 The protein kinase ERK3 is encoded by a single functional gene: genomic analysis of the ERK3 gene family. Genomics 17 12504858
2020 The C-Terminus Tail Regulates ERK3 Kinase Activity and Its Ability in Promoting Cancer Cell Migration and Invasion. International journal of molecular sciences 15 32516969
2019 TNF-α promotes tumor lymph angiogenesis in head and neck squamous cell carcinoma through regulation of ERK3. Translational cancer research 15 35116996
2004 Induction of p97MAPK expression regulates collagen mediated inhibition of proliferation and migration in human squamous cell carcinoma lines. International journal of oncology 15 15067337
2014 Administration of antenatal glucocorticoids and postnatal surfactant ameliorates respiratory distress syndrome-associated neonatal lethality in Erk3(-/-) mouse pups. Pediatric research 14 24732107
2001 Different domains of the mitogen-activated protein kinases ERK3 and ERK2 direct subcellular localization and upstream specificity in vivo. The Journal of biological chemistry 14 11741894
2015 The atypical MAPK ERK3 controls positive selection of thymocytes. Immunology 13 25521218
2021 ERK3 is transcriptionally upregulated by ∆Np63α and mediates the role of ∆Np63α in suppressing cell migration in non-melanoma skin cancers. BMC cancer 12 33579235
2020 Biochemical, cellular and structural characterization of novel and selective ERK3 inhibitors. Bioorganic & medicinal chemistry letters 12 32927028
2018 LncMAPK6 drives MAPK6 expression and liver TIC self-renewal. Journal of experimental & clinical cancer research : CR 12 29764463
2004 Molecular cloning, isolation and characterisation of ERK3 gene from chewing-tobacco induced oral squamous cell carcinoma. Oral oncology 12 15172640
2022 miR-128-3p inhibits the inflammation by targeting MAPK6 in penicillin-induced astrocytes. Neuroreport 11 36250437
2020 ERK3/MAPK6 is required for KRAS-mediated NSCLC tumorigenesis. Cancer gene therapy 11 33070159
2018 The atypical MAPK ERK3 potently suppresses melanoma cell growth and invasiveness. Journal of cellular physiology 11 30569573
2017 L290P/V mutations increase ERK3's cytoplasmic localization and migration/invasion-promoting capability in cancer cells. Scientific reports 11 29101390
2022 ERK3-MK5 signaling regulates myogenic differentiation and muscle regeneration by promoting FoxO3 degradation. Journal of cellular physiology 10 35141958
2024 Long non-coding RNA DANCR increases spinal cord neuron apoptosis and inflammation of spinal cord injury by mediating the microRNA-146a-5p/MAPK6 axis. European spine journal : official publication of the European Spine Society, the European Spinal Deformity Society, and the European Section of the Cervical Spine Research Society 9 38551688
2023 ERK3 Increases Snail Protein Stability by Inhibiting FBXO11-Mediated Snail Ubiquitination. Cancers 9 38201533
2021 LncRNA GAS6-AS2 promotes non-small-cell lung cancer cell proliferation via regulating miR-144-3p/ MAPK6 axis. Cell cycle (Georgetown, Tex.) 9 33459113
2020 CircRNA_100395 protects breast carcinoma deterioration by targeting MAPK6. European review for medical and pharmacological sciences 9 33336740
2020 Crystal Structure and Inhibitor Identifications Reveal Targeting Opportunity for the Atypical MAPK Kinase ERK3. International journal of molecular sciences 8 33114754
2005 Distribution of ERK1/2 and ERK3 during normal rat fetal lung development. Anatomy and embryology 8 16374608
2023 HNF4G increases cisplatin resistance in lung adenocarcinoma via the MAPK6/Akt pathway. PeerJ 7 36923501
2021 Conditional ERK3 overexpression cooperates with PTEN deletion to promote lung adenocarcinoma formation in mice. Molecular oncology 7 34719109
2020 let7f‑5p attenuates inflammatory injury in in vitro pneumonia models by targeting MAPK6. Molecular medicine reports 7 33300070
2018 MicroRNA-138 inhibits proliferation and induces apoptosis of laryngeal carcinoma via targeting MAPK6. European review for medical and pharmacological sciences 7 30229830
2025 Disturbed shear stress promotes atherosclerosis through TRIM21-regulated MAPK6 degradation and consequent endothelial inflammation. Clinical and translational medicine 6 39763069
2023 Increased methylation of ZNF671 suppresses tumor progression by promoting MAPK6 transcription in laryngeal carcinoma. International journal of biological sciences 6 37215982
2023 ERK3 and DGKζ interact to modulate cell motility in lung cancer cells. Frontiers in cell and developmental biology 6 37287450
2016 Structural and transcriptomic response to antenatal corticosteroids in an Erk3-null mouse model of respiratory distress. American journal of obstetrics and gynecology 6 27143398
2024 Role of the Atypical MAPK ERK3 in Cancer Growth and Progression. Cancers 5 38611058
2023 CircGAB1 Facilitates Podocyte Injury Through Sponging miR-346 and Activating MAPK6 in Diabetic Nephropathy. Applied biochemistry and biotechnology 5 37440116
2022 Phosphoproteomic analysis identifies supervillin as an ERK3 substrate regulating cytokinesis and cell ploidy. Journal of cellular physiology 5 36576983
2015 Analysis of ERK3 intracellular localization: dynamic distribution during mitosis and apoptosis. European journal of histochemistry : EJH 5 26708186
2024 The circ_0003928/miR-31-5p/MAPK6 cascade affects high glucose-induced inflammatory response, fibrosis and oxidative stress in HK-2 cells. Transplant immunology 4 38964515
2022 Targeting ERK3/MK5 complex for treatment of obesity and diabetes. Biochemical and biophysical research communications 4 35523049
1996 A specific association of ERK3 with B-Raf in rat hippocampus. Biochemical and biophysical research communications 4 8954940
2025 Anticancer Effects of MAPK6 siRNA-Loaded PLGA Nanoparticles in the Treatment of Breast Cancer. Journal of cellular and molecular medicine 3 39823246
2021 Neuroprotection by B355252 against Glutamate-Induced Cytotoxicity in Murine Hippocampal HT-22 Cells Is Associated with Activation of ERK3 Signaling Pathway. Biological & pharmaceutical bulletin 3 34719643
2020 Knockdown of long non-coding RNA TTTY15 protects cardiomyocytes from hypoxia-induced injury by regulating let-7b/MAPK6 axis. International journal of clinical and experimental pathology 3 32922590
2019 Correction to: LncMAPK6 drives MAPK6 expression and liver TIC self-renewal. Journal of experimental & clinical cancer research : CR 3 31861994
2019 A Radioactive in vitro ERK3 Kinase Assay. Bio-protocol 3 31930160
2018 The atypical mitogen-activated protein kinase ERK3 is essential for establishment of epithelial architecture. The Journal of biological chemistry 2 29674317
2025 SERPINA1 methylation as a novel diagnostic marker for early-stage papillary thyroid carcinoma via MAPK6-AKT/mTOR pathway. Clinical epigenetics 1 40442821
2025 Intracellular pH regulates ubiquitin-mediated degradation of the MAP kinase ERK3. Proceedings of the National Academy of Sciences of the United States of America 1 41123996
2024 ERK3 is involved in regulating cardiac fibroblast function. Physiological reports 1 38872461
2023 Triazolo[4,5-d]pyrimidin-5-amines based ERK3 inhibitors fail to demonstrate selective effects on adipocyte function. Archives of biochemistry and biophysics 1 37992885
2025 ERK3/MAPK6 promotes triple-negative breast cancer progression through collective migration and EMT plasticity. Frontiers in oncology 0 40936697

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