Affinage

MAPK4

Mitogen-activated protein kinase 4 · UniProt P31152

Length
587 aa
Mass
65.9 kDa
Annotated
2026-06-10
37 papers in source corpus 20 papers cited in narrative 20 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

MAPK4 (ERK4) is an atypical, constitutively active MAP kinase that functions as a stable upstream activator of MK5 and, in disease contexts, as a non-canonical driver of oncogenic AKT signaling (PMID:16971392, PMID:30688659). Its activation loop residue Ser186 within the SEG motif is phosphorylated in trans by an upstream kinase in resting cells rather than by autophosphorylation, and this phosphorylation stimulates intrinsic catalytic activity and gates the protein's signaling output (PMID:18248330, PMID:18720373); group I PAKs (PAK1/2/3) acting downstream of Rac1 are the responsible kinases (PMID:21177870). Phospho-Ser186 enables MAPK4 to bind MK5 through a non-canonical FRIEDE docking motif in the L16 extension, anchoring MK5 in the cytoplasm and directly phosphorylating and activating it, while ERK3 dimerization cooperatively reinforces MK5 activation (PMID:16973613, PMID:19473979). The dual-specificity phosphatase DUSP2 docks on the MAPK4 CD domain and dephosphorylates the activation loop, switching off the pathway (PMID:28252035). Separately, MAPK4 directly binds and phosphorylates AKT at Thr308 independent of PI3K and engages mTORC2 for Ser473 phosphorylation, and additionally enhances PDK1 protein synthesis, together driving anchorage-independent growth, tumor xenograft growth, and resistance to PI3K-pathway inhibitors across prostate and triple-negative breast cancers (PMID:30688659, PMID:35017531, PMID:37531320). In prostate cancer this AKT axis cooperates with MAPK4-mediated stabilization of GATA2 and androgen receptor activation to promote castration resistance (PMID:33586682). Genetic loss of Mapk4 in mice is compatible with viability and fertility but produces a depression-like behavioral phenotype, and Mapk4 also shapes inflammatory and angiogenic responses in multiple tissue contexts (PMID:20956558).

Mechanistic history

Synthesis pass · year-by-year structured walk · 13 steps
  1. 2006 High

    Established that the orphan atypical kinase ERK4 has a defined substrate by identifying MK5 as its binding partner and demonstrating catalysis-dependent activation, answering what ERK4 actually does.

    Evidence Reciprocal Co-IP, catalytically dead mutants, and siRNA knockdown with kinase activity readouts in HEK293/HeLa cells, replicated by two independent labs

    PMID:16971392 PMID:16973613

    Open questions at the time
    • The upstream kinase activating ERK4 was unknown
    • Structural basis of the ERK4-MK5 interaction not yet defined
  2. 2008 High

    Resolved how ERK4 is regulated by showing that activation-loop Ser186 is phosphorylated in trans in resting cells and is required for MK5 binding, cytoplasmic anchoring, and activation.

    Evidence In vivo phosphorylation assays, phospho-mutant constructs, mobility-shift, Co-IP and localization assays across two studies

    PMID:18248330 PMID:18720373

    Open questions at the time
    • Identity of the upstream Ser186 kinase unresolved
    • Why phosphorylation is constitutive rather than stimulus-induced not explained
  3. 2009 High

    Defined the molecular docking mechanism by identifying the non-canonical FRIEDE motif, not the canonical CD domain, as the MK5-binding interface gated by activation-loop phosphorylation.

    Evidence Peptide overlay assays, FRIEDE point mutagenesis, Co-IP, localization, and kinase activity assays

    PMID:19473979

    Open questions at the time
    • No structural model of the phospho-gated FRIEDE switch
    • Whether other partners use this docking site untested
  4. 2010 High

    Identified the long-sought upstream kinase, placing ERK4 in a Rac1-PAK-ERK4-MK5 signaling cascade.

    Evidence Biochemical kinase purification, in vitro kinase assays, siRNA of PAK1/2/3, and activated Rac1 expression

    PMID:21177870

    Open questions at the time
    • Physiological stimuli engaging Rac1-PAK to control ERK4 not mapped
    • Tissue contexts where this cascade operates unknown
  5. 2010 High

    Defined the organismal role of Mapk4 through knockout, revealing a non-redundant behavioral function distinct from Erk3.

    Evidence Targeted Mapk4 disruption in mice with developmental, physiological, and forced-swim behavioral phenotyping

    PMID:20956558

    Open questions at the time
    • Molecular basis of the depression-like phenotype unexplained
    • Whether the MK5 axis underlies the behavioral effect untested
  6. 2017 High

    Identified the off-switch of the pathway by showing DUSP2 dephosphorylates the ERK4 activation loop via CD-domain docking, with reciprocal stabilization of DUSP2.

    Evidence Co-IP, direct binding, dephosphorylation assays, DUSP2 stability measurements, and MK5 activity readouts

    PMID:28252035

    Open questions at the time
    • Physiological signals controlling DUSP2-ERK4 engagement unknown
    • Whether DUSP2 regulates the AKT branch untested
  7. 2019 High

    Revealed a non-canonical oncogenic function by showing MAPK4 directly phosphorylates AKT T308 independent of PI3K and engages mTORC2 for S473, transforming cells.

    Evidence Co-IP, in vitro kinase assays, phospho-specific blotting, mutagenesis, xenografts, and TCGA correlation

    PMID:30688659

    Open questions at the time
    • How MAPK4 recruits/activates mTORC2 mechanistically unresolved
    • Relationship between the MK5 and AKT branches unclear
  8. 2020 Medium

    Extended the MAPK4-AKT axis to therapeutic vulnerabilities, placing MAPK4 upstream of AKT-dependent DNA repair and inflammatory/radiation responses.

    Evidence CRISPR KO with constitutively active AKT rescue in cervical cancer; knockout mice in LPS-induced acute lung injury with multi-pathway signaling readouts

    PMID:32711558 PMID:33088477

    Open questions at the time
    • Direct versus indirect control of DNA repair factors not separated
    • Tissue-specific kinase substrates beyond AKT undefined
  9. 2021 High

    Established a second oncogenic branch in prostate cancer, showing MAPK4 stabilizes GATA2 and activates AR cooperatively with AKT to drive castration resistance.

    Evidence Ubiquitination assays, knockdown/overexpression, xenografts, and CRPC patient correlation

    PMID:33586682

    Open questions at the time
    • Mechanism by which MAPK4 represses GATA2 ubiquitination unknown
    • Whether GATA2 stabilization is kinase-dependent untested
  10. 2022 High

    Generalized MAPK4 as a PI3K-bypass mechanism, demonstrating that its depletion sensitizes TNBC to PI3K inhibitors.

    Evidence siRNA/shRNA knockdown, AKT phosphorylation assays, PI3K inhibitor sensitivity, and xenografts

    PMID:35017531

    Open questions at the time
    • Predictive biomarkers for MAPK4-driven PI3K resistance undefined
    • Combination dosing strategies not optimized
  11. 2023 Medium

    Broadened MAPK4 oncogenic output beyond AKT by linking it to PDK1 protein synthesis and to a macrophage-driven metastatic feedback loop.

    Evidence Protein synthesis and PDK1 substrate assays with drug resistance studies in TNBC; orthotopic gastric cancer models with MIF/TAM profiling

    PMID:36797541 PMID:37531320

    Open questions at the time
    • How MAPK4 enhances PDK1 translation mechanistically unknown
    • The MIF-TAM feedback effectors downstream of MAPK4 not fully defined
  12. 2024 Medium

    Documented context-specific and nuclear functions of MAPK4 in angiogenesis and neurodegeneration, expanding its roles beyond cancer cell-intrinsic AKT signaling.

    Evidence Endothelial-specific CD34-driven siRNA in NSCLC tumor models with ERK1/2 readouts; nuclear fractionation, MAPK4-GATA2 Co-IP and SNCA reporter assays in MC-LR exposure models

    PMID:38947754 PMID:39738876

    Open questions at the time
    • How MAPK4 suppresses endothelial ERK1/2 mechanistically unknown
    • Trigger and regulation of MAPK4 nuclear translocation undefined
  13. 2025 Medium

    Revealed immunoregulatory and pharmacologically tractable roles, with MAPK4 restraining BCR/PI3K signaling via IRF4-SHIP1 and serving as a druggable AKT-interaction node in inflammation.

    Evidence Knockout mice with Vacquinol-1 agonist in arthritis models; Co-IP disruption by spermidine derivative in colitis models

    PMID:39863600 PMID:40238233

    Open questions at the time
    • Reconciliation of MAPK4 inhibiting versus activating AKT across cell types unresolved
    • The colitis MAPK4-AKT claim rests on a single Co-IP method

Open questions

Synthesis pass · forward-looking unresolved questions
  • How MAPK4 switches between its MK5 axis and its AKT/PDK1/GATA2 axes, and what determines its opposing effects on AKT in different cell types, remains unresolved.
  • No structural model of the MAPK4-AKT or MAPK4-mTORC2 interaction
  • Determinants of context-dependent positive versus negative regulation of PI3K-AKT undefined
  • Whether the constitutive Rac1-PAK input controls the oncogenic branches untested

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 3 GO:0140096 catalytic activity, acting on a protein 3 GO:0140110 transcription regulator activity 2
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 1
Pathway
R-HSA-1643685 Disease 3 R-HSA-162582 Signal Transduction 2 R-HSA-168256 Immune System 2
Partners
AKT1DUSP2ERK3GATA2MK5PAK1

Evidence

Reading pass · 20 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2006 ERK4 (MAPK4) binds to endogenous MK5 (MAPKAP kinase 5), and this interaction leads to translocation of MK5 to the cytoplasm and activation of MK5 by phosphorylation. Unlike ERK3, ERK4 is a stable protein, and its catalytic activity is necessary for MK5 activation (catalytically dead ERK4 cannot activate MK5). ERK4 also dimerizes/oligomerizes with ERK3, suggesting cooperative activation of MK5. Co-immunoprecipitation, transfection of catalytically dead mutants in HEK293 cells, subcellular localization assays The Journal of biological chemistry High 16973613
2006 ERK4 (MAPK4) is a bona fide interaction partner of MK5. Binding of ERK4 to MK5 results in phosphorylation and activation of MK5 and relocalization of MK5 from nucleus to cytoplasm. Knockdown of ERK4 in HeLa cells reduces endogenous MK5 activity by ~50%; combined knockdown of ERK4 and ERK3 reduces MK5 activity by >80%, establishing both as physiological regulators of MK5. Co-immunoprecipitation, siRNA knockdown, subcellular localization assays, kinase activity assays The Journal of biological chemistry High 16971392
2008 Ser186 within the SEG activation loop motif of ERK4 (MAPK4) is phosphorylated in vivo by an upstream kinase (not autophosphorylation). This phosphorylation is required for the interaction with MK5, for cytoplasmic anchoring of MK5, and for activation of MK5. Alanine or glutamate substitution at Ser186 abrogates ERK4-MK5 complex formation and MK5 activation. Co-expression of MK5 increases Ser186 phosphorylation, suggesting MK5 binding facilitates ERK4 phosphorylation. In vivo phosphorylation assays, kinase-dead and phospho-mutant ERK4 constructs, Co-immunoprecipitation, subcellular localization assays, SDS-PAGE mobility shift analysis The Biochemical journal High 18248330
2008 Activation loop phosphorylation of ERK4 (MAPK4) at Ser186 (SEG motif) is detected in resting cells and is not further stimulated by mitogenic or stress stimuli. This phosphorylation stimulates intrinsic catalytic activity of ERK4 and is required for formation of stable active complexes with MK5 and for cytoplasmic redistribution of ERK4-MK5 complexes. Phosphorylation is exerted in trans by an upstream cellular kinase. In vivo phosphorylation, pharmacological and mutant analyses, kinase activity assays, co-immunoprecipitation, subcellular fractionation Journal of cellular physiology High 18720373
2009 ERK4 (MAPK4) interacts with MK5 via a novel interaction motif 'FRIEDE' located in the L16 extension C-terminal to the CD domain. The canonical CD domain is dispensable for ERK3/4-MK5 interaction. A single isoleucine-to-lysine substitution in FRIEDE abolishes binding, activation, and translocation of MK5 by ERK4. Activation loop phosphorylation gates accessibility of the FRIEDE motif, suggesting a phosphorylation-dependent switch mechanism. Peptide overlay assays, site-directed mutagenesis of FRIEDE motif, Co-immunoprecipitation, subcellular localization assays, kinase activity assays The Journal of biological chemistry High 19473979
2010 Group I p21-activated kinases (PAK1, PAK2, PAK3) phosphorylate ERK4 (MAPK4) on its activation loop residue Ser186 both in vitro and in vivo, thereby activating ERK4. Expression of activated Rac1 augments this phosphorylation; siRNA silencing of PAK1/2/3 abolishes Rac1-induced ERK4 Ser186 phosphorylation. PAK-mediated phosphorylation of ERK4 results in downstream activation of MK5, defining a PAK-ERK4-MK5 signaling pathway. Biochemical kinase purification, in vitro kinase assays, siRNA knockdown, expression of activated Rac1, in vivo phosphorylation assays The Journal of biological chemistry High 21177870
2010 Mapk4-knockout mice are viable and fertile with no gross morphological or physiological anomalies. Loss of Erk4 does not alter Erk3 expression or activity and does not exacerbate Erk3-null phenotypes (fetal growth restriction, pulmonary immaturity). However, Erk4-deficient mice display depression-like behavior in the forced-swimming test, indicating a specific non-redundant behavioral function. Targeted gene disruption in mice (Mapk4 knockout), developmental and physiological phenotyping, behavioral tests (forced-swimming), western blotting Molecular and cellular biology High 20956558
2017 The dual-specificity phosphatase DUSP2 binds directly to ERK4 (MAPK4) via interaction between the DUSP2 kinase interaction motif (KIM) and the conserved CD domain of ERK4. This interaction results in dephosphorylation of ERK4's activation loop and stabilization of DUSP2. ERK4 kinase activity is required for DUSP2 stabilization. DUSP2 expression inhibits ERK4-mediated activation of MK5. Co-immunoprecipitation, direct binding assays, phosphorylation assays, DUSP2 stability measurements, kinase-dead ERK4 mutants, MK5 activity assays Scientific reports High 28252035
2019 MAPK4 directly binds and phosphorylates AKT at threonine 308 (activation loop) independent of PI3K. MAPK4 also activates mTORC2 to phosphorylate AKT at serine 473, enabling full AKT activation. This non-canonical AKT activation promotes oncogenic outcomes including anchorage-independent growth. MAPK4 overexpression transforms prostate epithelial cells; MAPK4 knockdown inhibits cancer cell proliferation and xenograft growth. Co-immunoprecipitation, in vitro kinase assays, phospho-specific western blotting, site-directed mutagenesis, xenograft tumor models, TCGA correlation analysis The Journal of clinical investigation High 30688659
2021 MAPK4 activates the androgen receptor (AR) by enhancing GATA2 transcriptional expression and stabilizing GATA2 protein through repression of GATA2 ubiquitination and degradation. Concerted activation of both GATA2/AR and AKT pathways by MAPK4 promotes prostate cancer cell proliferation, anchorage-independent growth, xenograft growth, and castration resistance. Both pathways are necessary for MAPK4 tumor-promoting activity. Western blotting, ubiquitination assays, gene knockdown and overexpression, xenograft mouse models, CRPC patient sample correlation The Journal of clinical investigation High 33586682
2022 MAPK4 drives AKT activation independent of PI3K in a large subset of triple-negative breast cancer (TNBC) cells. MAPK4 expression is critical for TNBC cell and xenograft growth. Repressing MAPK4 sensitizes TNBC cells and xenografts to PI3K inhibitors by removing a PI3K-bypass mechanism for AKT activation. siRNA/shRNA knockdown, AKT phosphorylation assays, PI3K inhibitor drug sensitivity assays, xenograft mouse models Nature communications High 35017531
2023 MAPK4 also enhances PDK1 protein synthesis, thereby phosphorylating/activating PDK1 substrates beyond AKT. This MAPK4-PDK1 axis cooperates with the MAPK4-AKT axis to promote tumor growth and confer resistance to both PI3K and PI3K/PDK1 co-blockade in TNBC cells. Protein synthesis assays, PDK1 substrate phosphorylation assays, siRNA knockdown, drug resistance assays in TNBC cell models PLoS biology Medium 37531320
2023 MAPK4 depletion in gastric cancer cells induces secretion of macrophage migration inhibitory factor (MIF), which polarizes tumor-associated macrophages (TAMs). In turn, TAMs activate epithelial-mesenchymal transition in gastric cancer cells and suppress MAPK4 expression, creating a positive feedback loop that facilitates liver metastasis in orthotopic mouse models. In vivo orthotopic mouse models, shRNA knockdown, cytokine measurement (MIF secretion), transcriptome profiling, tissue array analysis Experimental & molecular medicine Medium 36797541
2020 MAPK4 knockout reduces AKT phosphorylation in cervical cancer cells, impairing DNA repair signaling (reduced p-DNA-PK and RAD51), which enhances radiation sensitivity and sensitivity to PARP1 inhibitors. Constitutively active AKT rescues DNA repair protein expression in MAPK4 KO cells, placing MAPK4 upstream of AKT in this DNA repair context. CRISPR knockout, western blotting, colony formation assay, immunofluorescence, xenograft mouse models, constitutively active AKT rescue experiments Journal of experimental & clinical cancer research Medium 32711558
2020 MAPK4 deficiency in mice reduces signaling through MK5, AKT, JNK, and p38 MAPK pathways in LPS-induced acute lung injury. MAPK4 KO mice show prolonged survival, reduced pro-inflammatory cytokines, and altered immune cell composition in bronchoalveolar lavage fluid. MAPK4 expression in macrophages is upregulated by LPS, and MAPK4 knockdown reduces pro-inflammatory cytokine expression in macrophages. MAPK4 knockout mice, LPS-induced ALI model, shRNA knockdown in macrophages, signaling pathway analysis by western blot, cytokine measurement Cell & bioscience Medium 33088477
2024 MAPK4 silencing in endothelial cells inhibits their proliferation and migration, and increases ERK1/2 pathway signaling (but not AKT or JNK). In vivo, targeted silencing of MAPK4 in endothelial cells using CD34 promoter-driven siRNA inhibits tumor angiogenesis and NSCLC growth, indicating MAPK4 facilitates angiogenesis partly by suppressing ERK1/2 signaling in endothelial cells. siRNA knockdown, flow cytometry, immunofluorescence, whole-genome transcriptional analysis, western blotting, in vivo tumor model with CD34 promoter-driven siRNA Cancer innovation Medium 38947754
2024 MAPK4 translocates to the nucleus in response to MC-LR exposure and binds to the GATA2 protein (residues 295-480), enhancing SNCA gene transcription and thereby increasing α-synuclein protein expression, contributing to Lewy body formation and Parkinson's-like pathology. Nuclear fractionation, co-immunoprecipitation of MAPK4 and GATA2, luciferase reporter assay for SNCA transcription, western blotting, in vitro and in vivo MC-LR exposure models Molecular neurobiology Medium 39738876
2025 MAPK4 inhibits PI3K-AKT-mTOR signaling in B cells by activating the IRF4-SHIP1 pathway. MAPK4 KO mice show enhanced proximal BCR signaling, heightened B cell proliferation, higher IL-6 production, and impaired marginal zone B cell differentiation. The MAPK4 agonist Vacquinol-1 enhances MZ B cell differentiation and reduces IL-6 secretion in collagen-induced arthritis models. MAPK4 knockout mice, pharmacological agonist (Vacquinol-1), flow cytometry, cytokine measurement, signaling pathway analysis by western blotting, collagen-induced arthritis model Cell death & disease Medium 39863600
2024 FUS RNA binding protein stabilizes MAPK4 mRNA in TNBC cells, as shown by RNA immunoprecipitation. Puerarin treatment downregulates both FUS and MAPK4, and MAPK4 overexpression attenuates puerarin's anti-tumor effects, placing FUS upstream of MAPK4 in this regulatory axis. RNA immunoprecipitation (RIP) assay, western blotting, qRT-PCR, overexpression rescue experiments, xenograft mouse model Chemical biology & drug design Medium 39223105
2025 A spermidine derivative (SPDD) weakens the interaction between MAPK4 and AKT, resulting in decreased AKT phosphorylation and reduced expression of IL-6, IL-1β, iNOS, and COX-2, thereby alleviating colitis. This places MAPK4 as a direct physical mediator of AKT activation in the inflammatory context. Co-immunoprecipitation (MAPK4-AKT interaction assay), RNA-seq, western blotting, DSS-induced colitis mouse model, Caco-2 cell inflammation model Foods (Basel, Switzerland) Low 40238233

Source papers

Stage 0 corpus · 37 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2020 Circular RNA MAPK4 (circ-MAPK4) inhibits cell apoptosis via MAPK signaling pathway by sponging miR-125a-3p in gliomas. Molecular cancer 115 31992303
2019 CircRNA circ_0000190 inhibits the progression of multiple myeloma through modulating miR-767-5p/MAPK4 pathway. Journal of experimental & clinical cancer research : CR 107 30728056
2019 MAPK4 overexpression promotes tumor progression via noncanonical activation of AKT/mTOR signaling. The Journal of clinical investigation 77 30688659
2006 Characterization of the atypical MAPK ERK4 and its activation of the MAPK-activated protein kinase MK5. The Journal of biological chemistry 74 16973613
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
2006 Regulation of MAPK-activated protein kinase 5 activity and subcellular localization by the atypical MAPK ERK4/MAPK4. The Journal of biological chemistry 64 16971392
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
2021 MAPK4 promotes prostate cancer by concerted activation of androgen receptor and AKT. The Journal of clinical investigation 46 33586682
2014 Linear B-cell epitope mapping of MAPK3 and MAPK4 from Leishmania braziliensis: implications for the serodiagnosis of human and canine leishmaniasis. Applied microbiology and biotechnology 40 25359475
2022 MAPK4 promotes triple negative breast cancer growth and reduces tumor sensitivity to PI3K blockade. Nature communications 37 35017531
2019 MiR-127 attenuates adipogenesis by targeting MAPK4 and HOXC6 in porcine adipocytes. Journal of cellular physiology 37 31206669
2019 Identification of lead molecules against potential drug target protein MAPK4 from L. donovani: An in-silico approach using docking, molecular dynamics and binding free energy calculation. PloS one 37 31425543
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
2023 MAPK4 silencing in gastric cancer drives liver metastasis by positive feedback between cancer cells and macrophages. Experimental & molecular medicine 28 36797541
2017 Regulation of atypical MAP kinases ERK3 and ERK4 by the phosphatase DUSP2. Scientific reports 26 28252035
2020 MAPK4 deletion enhances radiation effects and triggers synergistic lethality with simultaneous PARP1 inhibition in cervical cancer. Journal of experimental & clinical cancer research : CR 25 32711558
2008 The Ser(186) phospho-acceptor site within ERK4 is essential for its ability to interact with and activate PRAK/MK5. The Biochemical journal 24 18248330
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
2020 MiR-127-3p inhibits proliferation of ovarian cancer in rats through down-regulating MAPK4. European review for medical and pharmacological sciences 18 33155194
2024 A review of non-classical MAPK family member, MAPK4: A pivotal player in cancer development and therapeutic intervention. International journal of biological macromolecules 17 38801852
2020 Identification of atypical mitogen-activated protein kinase MAPK4 as a novel regulator in acute lung injury. Cell & bioscience 13 33088477
2024 Microcystin-LR Exposure Damages Neurons by Inducing α-Syn Aggregation via MAPK4/GATA2/SNCA and PP2A/GRKs Pathways. Molecular neurobiology 12 39738876
2023 Cooperative activation of PDK1 and AKT by MAPK4 enhances cancer growth and resistance to therapy. PLoS biology 12 37531320
2022 The silencing of miR-199a-5p protects the articular cartilage through MAPK4 in osteoarthritis. Annals of translational medicine 12 35722355
2021 MAPK4 silencing together with a PARP1 inhibitor as a combination therapy in triple‑negative breast cancer cells. Molecular medicine reports 10 34080025
2025 Human umbilical cord mesenchymal stem cell-derived exosomal miR-199a-3p inhibits the MAPK4/NF-κB signaling pathway to relieve osteoarthritis. World journal of stem cells 7 40308884
2020 Association of MAPK4 and SOX1-OT gene polymorphisms with cleft lip palate in multiplex families: A genetic study. Journal of dental research, dental clinics, dental prospects 6 32908649
2025 MAPK4 inhibits the early aberrant activation of B cells in rheumatoid arthritis by promoting the IRF4-SHIP1 signaling pathway. Cell death & disease 5 39863600
2022 miR-576-5p Promotes the Proliferation of Papillary Thyroid Carcinoma through the MAPK4-AKT Pathway. International journal of analytical chemistry 5 36618768
2024 Leishmania major MAPK4 intercepts and redirects CD40 signaling promoting infection. International immunopharmacology 3 38728877
2024 MAPK4 facilitates angiogenesis by inhibiting the ERK pathway in non-small cell lung cancer. Cancer innovation 3 38947754
2024 Puerarin Decreases the Expression of FUS-Dependent MAPK4 to Inhibit the Development of Triple-Negative Breast Cancer. Chemical biology & drug design 3 39223105
2022 On the Therapeutic Potential of ERK4 in Triple-Negative Breast Cancer. Cancers 3 36612022
2025 Regulation of diabetic disc degeneration: The role of AGEAT/miR-204-5p/Mapk4 axis in nucleus pulposus cells' mitochondrial function and apoptosis. Cellular signalling 2 40381974
2023 LINC00467 enhanced the proliferative, migratory and invasive ability of breast cancer cells by targeting miR-18a/b-5p/MAPK4 axis. Cellular and molecular biology (Noisy-le-Grand, France) 2 38279470
2025 A Spermidine Derivative Ameliorates Dextran Sulfate Sodium-Induced Colitis in Mice by Inhibiting the MAPK4/AKT Signaling Pathway. Foods (Basel, Switzerland) 1 40238233
2023 Genetic Polymorphisms of rs9949644 in MAPK4 Are Associated with Clinical Response to Methotrexate in Patients with Psoriasis. Dermatology (Basel, Switzerland) 1 37494889

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