Affinage

MAP2K5

Dual specificity mitogen-activated protein kinase kinase 5 · UniProt Q13163

Length
448 aa
Mass
50.1 kDa
Annotated
2026-04-28
91 papers in source corpus 42 papers cited in narrative 42 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAP2K5 (MEK5) is a dual-specificity MAP kinase kinase that serves as the obligate and specific activator of ERK5/BMK1, transducing signals from MEKK2/MEKK3 through PB1-domain-mediated heterodimerization to regulate cell survival, differentiation, cardiac development, and stress responses (PMID:7499418, PMID:12912994, PMID:15601854). MEKK2 and MEKK3 bind MEK5 via front-to-back PB1 domain interactions (Kd ~10⁻⁸ M), with a C-terminal extension of the MEK5 PB1 domain encoding an ERK5 docking site essential for substrate activation; this cascade is negatively regulated by XIAP/cIAP1-mediated K63-linked ubiquitination of MEKK2/3, which disrupts the MEK5–ERK5 interaction (PMID:17452462, PMID:17985933, PMID:24975362). MEK5-activated ERK5 phosphorylates transcription factors including MEF2C, c-Fos/Fra-1, and KLF4, and stabilizes MYC via S62 phosphorylation; MEK5 also promotes DNA-PK-dependent NHEJ repair, controls lipid/cholesterol metabolism, drives M2 macrophage differentiation through c-Myc, and maintains basal mitochondrial degradation (PMID:12622723, PMID:30423298, PMID:31980741, PMID:32745297, PMID:33101709, PMID:31969375). Targeted deletion of Mek5 in mice causes embryonic lethality at ~E10.5 with cardiac defects, and Map2k5 knockout mice exhibit dopaminergic neuron loss with motor and sensorimotor gating deficits (PMID:15601854, PMID:34168549).

Mechanistic history

Synthesis pass · year-by-year structured walk · 19 steps
  1. 1995 High

    Identification of MEK5 as a novel MAP kinase kinase in a distinct signaling module resolved the question of whether additional MAPK cascades existed beyond the ERK1/2, JNK, and p38 pathways, revealing two splice isoforms (α and β) with distinct subcellular distributions.

    Evidence PCR cloning, in vitro substrate phosphorylation assays, and subcellular fractionation in multiple tissues

    PMID:7499418

    Open questions at the time
    • The specific MAPK substrate of MEK5 was not yet identified
    • No upstream kinase activating MEK5 was known
    • Physiological roles were undefined
  2. 1999 High

    Identification of MEKK3 and Raf-1 as upstream regulators of the MEK5–ERK5 cascade established the three-tier architecture of this pathway and its link to Ras-driven transformation.

    Evidence Yeast two-hybrid, co-immunoprecipitation, dominant-active/kinase-dead MEKK3 mutants, NIH 3T3 transformation assay with constitutively active MEK5

    PMID:10531364 PMID:10593883

    Open questions at the time
    • The molecular basis of MEKK3–MEK5 binding was unknown
    • Whether MEKK2 also activates MEK5 was untested
  3. 2000 High

    Demonstration that MEKK2 binds and activates MEK5–ERK5 more potently than MEKK3 broadened the upstream input map and showed MEK5 is the specific mediator of MEKK2-to-ERK5 signaling.

    Evidence Yeast two-hybrid, co-immunoprecipitation, dominant-negative MEK5 selectively blocking MEKK2-induced ERK5 without affecting JNK

    PMID:11073940

    Open questions at the time
    • Structural basis for MEKK2/3 selectivity for MEK5 over other MKKs was unclear
  4. 2001 High

    Constitutive MEK5 activation in cardiomyocytes induced serial sarcomere assembly and eccentric hypertrophy progressing to dilated cardiomyopathy in transgenic mice, establishing the first in vivo physiological role for MEK5–ERK5 signaling.

    Evidence Adenoviral CA/DN MEK5 in cardiomyocytes, cardiac-specific MEK5 transgenic mice with morphological and functional cardiac analysis

    PMID:11387209

    Open questions at the time
    • Whether endogenous MEK5 is essential for cardiac development required loss-of-function genetics
    • Downstream transcriptional effectors in the heart were not defined
  5. 2003 High

    PB1-domain-mediated heterodimerization was identified as the structural mechanism coupling MEKK2/3 to MEK5, with specificity encoded by complementary basic (MEKK2/3) and acidic (MEK5) surfaces on ubiquitin-fold PB1 domains.

    Evidence In vitro PB1 domain binding, co-immunoprecipitation, mutagenesis of PB1 domains, dominant-interference experiments, NMR structures

    PMID:12912994 PMID:15143057 PMID:17985933

    Open questions at the time
    • Full-length MEKK2/3–MEK5–ERK5 ternary complex structure was not resolved
    • How PB1 domain interaction is regulated dynamically in cells was unclear
  6. 2003 Medium

    MEK5–ERK5 was shown to regulate transcription factor outputs including c-Fos/Fra-1 stabilization and AP-1/MMP-9 transcription, connecting the pathway to gene expression programs for invasion and proliferation.

    Evidence CA-MEK5, phosphorylation assays, reporter assays, EMSA, invasion assays in prostate cancer cells

    PMID:12618764 PMID:12622723

    Open questions at the time
    • Direct ERK5 phosphorylation sites on c-Fos were mapped but not confirmed by mass spectrometry
    • Whether MEK5 regulates AP-1 independently of ERK5 was not addressed
  7. 2004 High

    Endogenous MEK5 and ERK5 were found to reside predominantly in the nucleus bound to detergent-resistant structures, revising the assumption that the cascade signals only from the cytoplasm.

    Evidence Immunofluorescence, in situ NP-40 extraction, subcellular fractionation in HeLa and Rat-1 cells

    PMID:15075238

    Open questions at the time
    • Nuclear substrates of MEK5 beyond ERK5 were not identified
    • Whether nuclear MEK5 has kinase-independent scaffolding functions was untested
  8. 2005 High

    Genetic knockout of Mek5 proved it is essential for embryonic viability and cardiac development, and demonstrated that MEK5 is the non-redundant upstream activator of ERK5 and MEF2 transcriptional activity, with a pro-survival role against stress-induced apoptosis.

    Evidence Mek5 knockout mice (lethal ~E10.5), MEF analysis of ERK5 activation, MEF2 reporter assays, caspase-3 activity assays

    PMID:15601854

    Open questions at the time
    • Conditional knockouts in specific tissues were not yet available
    • Whether other kinases partially compensate in non-cardiac tissues was unclear
  9. 2005 High

    MEK5–ERK5 was positioned as a key driver of neural differentiation downstream of SoxD in Xenopus, demonstrating conservation of its developmental signaling role across vertebrates.

    Evidence Morpholino knockdown of MEK5/ERK5 and constitutively active MEK5 in Xenopus embryos

    PMID:16179948

    Open questions at the time
    • Direct phosphorylation targets of ERK5 in neural progenitors were not identified
    • Whether MEK5 has mammalian neural differentiation roles was not yet shown in knockout models
  10. 2007 High

    Detailed domain mapping revealed that a 34-amino-acid extension C-terminal to the MEK5 PB1 domain encodes the ERK5 docking site, and that MEKK2 switches between MEK5 and MKK7 binding upon activation, explaining how the PB1 module achieves pathway specificity.

    Evidence Domain interaction mapping, mutagenesis, co-immunoprecipitation, kinase assays

    PMID:17452462

    Open questions at the time
    • Atomic-resolution structure of the MEK5 PB1-ERK5 docking interaction was not solved
    • How activation-dependent conformational change in MEKK2 triggers partner switching was not mechanistically defined
  11. 2008 High

    MEK5 was shown to antagonize ERK5 SUMOylation at K6/K22 through physical association (independently of its kinase activity), while BIX02188/BIX02189 were validated as selective MEK5 catalytic inhibitors, providing both a kinase-independent regulatory mechanism and pharmacological tools.

    Evidence SUMOylation-site mutants, siRNA-PIAS1, DN-Ubc9, transgenic mice; purified MEK5 in vitro kinase assays with BIX compounds, cell-based selectivity assays

    PMID:18467627 PMID:18834865

    Open questions at the time
    • Whether SUMOylation-regulated ERK5 activity and kinase-dependent ERK5 activity converge on the same targets was unclear
    • BIX compound selectivity against the full kinome was not comprehensively profiled
  12. 2008 Medium

    MEK5–ERK5 was identified as the pathway mediating flow-mediated inhibition of JNK in endothelial cells and as a driver of EMT in breast cancer, expanding its roles to vascular mechanotransduction and cancer metastasis.

    Evidence Selective MEK5 inhibitor BIX02188 in shear stress assays; MEK5 overexpression with proteomics and ERK5 shRNA in breast cancer cells

    PMID:18358237 PMID:19087274

    Open questions at the time
    • Direct endothelial substrates of ERK5 mediating JNK crosstalk were not identified
    • EMT gene regulation by ERK5 was correlative without defined direct transcriptional targets
  13. 2011 Medium

    MEK5/ERK5 was shown to induce KLF4 in endothelial cells under shear stress, establishing a transcription factor link to anti-inflammatory vascular protection.

    Evidence Laminar shear stress, CA-MEK5, siRNA knockdown of ERK5 and KLF4 in dermal microvascular endothelial cells

    PMID:21166929

    Open questions at the time
    • Whether ERK5 directly phosphorylates KLF4 or acts through intermediate transcription factors was not determined
  14. 2014 High

    XIAP/cIAP1-mediated K63-linked ubiquitination of MEKK2/3 was identified as a negative regulatory mechanism that disrupts the MEKK2/3–MEK5–ERK5 trimeric complex, adding an E3-ligase-based layer of pathway control relevant to myoblast differentiation.

    Evidence Ubiquitination assays with linkage analysis, competition binding experiments, XIAP/cIAP1 knockdown/knockout, myoblast differentiation assay

    PMID:24975362

    Open questions at the time
    • Whether other E3 ligases regulate the same complex was not tested
    • Deubiquitinase(s) counteracting this modification were not identified
  15. 2018 High

    MEK5–ERK5 was shown to stabilize MYC via ERK5-mediated S62 phosphorylation in PDAC, revealing a feedforward survival mechanism activated when ERK1/2 is inhibited.

    Evidence Kinome-wide proteomics, high-throughput MYC degradation screen, MEK5/ERK5 inhibitors, phospho-MYC S62 assays in PDAC cells

    PMID:30423298

    Open questions at the time
    • Whether this MEK5–ERK5–MYC axis operates in non-PDAC contexts was not established
    • Direct ERK5-MYC phosphorylation was shown but in vitro kinase assay with purified components was not presented
  16. 2019 High

    MEK5 was found to promote DNA-PK Ser2056 phosphorylation and nonhomologous end joining (NHEJ) repair, revealing a role in the DNA damage response independent of its canonical ERK5 transcriptional outputs.

    Evidence MEK5 siRNA knockdown, DNA-PK phosphorylation assays, γH2AX/53BP1 foci kinetics, cell-based NHEJ assay, clonogenic survival, xenograft validation

    PMID:31980741

    Open questions at the time
    • Whether MEK5 regulates DNA-PK directly or through ERK5 was not resolved
    • The phosphorylation event linking MEK5 to DNA-PK Ser2056 was not reconstituted in vitro
  17. 2020 High

    MEK5–ERK5 was shown to control M2 macrophage differentiation via c-Myc (independent of STAT3/6) and to maintain basal mitochondrial degradation through lysosome-mediated turnover, expanding the pathway's roles to innate immunity and organelle homeostasis.

    Evidence Myeloid-specific Erk5 conditional knockout mice, MEK5/ERK5 inhibitors, CRISPR knockout, mitochondrial content quantification, lysosome degradation assays

    PMID:32745297 PMID:33101709

    Open questions at the time
    • The mitochondrial substrate or receptor targeted by ERK5 for lysosomal degradation was not identified
    • Whether MEK5 has ERK5-independent roles in macrophage polarization was not tested
  18. 2021 Medium

    Map2k5 knockout mice showed dopaminergic neuron loss and motor/sensorimotor gating deficits, establishing an in vivo requirement for MEK5 in dopaminergic neuron survival and extending the pathway beyond developmental neurobiology to neurodegeneration-relevant phenotypes.

    Evidence Targeted Map2k5 knockout mouse model, behavioral testing, tyrosine hydroxylase immunohistochemistry

    PMID:34168549

    Open questions at the time
    • Mechanism of dopaminergic cell death (apoptosis vs. other) was not defined
    • Whether ERK5 activation is reduced in these knockout brains was not directly shown
    • Single study without independent replication
  19. 2025 Medium

    MEK5–ERK5 was shown to activate the Hedgehog-GLI pathway in melanoma and to cooperate with ERK1/2 to maintain Cyclin D1/CDK4 expression, while full-length MEK5 mRNA integrity was found to depend on the splicing factor RBM39 for NF-κB-mediated survival in myeloma.

    Evidence MEK5DD overexpression, ERK5 shRNA, GLI reporter assays, 3D spheroid assays; MEKi/ERK5i co-inhibition with Cyclin D1/CDK4 rescue; RBM39 knockdown/degradation with splicing analysis and p65 activity assays

    PMID:39998753 PMID:40048740 PMID:41053077

    Open questions at the time
    • Whether ERK5 directly phosphorylates GLI1/2 was not established
    • The exact mis-spliced MEK5 isoforms from RBM39 loss require further characterization
    • Whether combined MEKi/ERK5i approaches have clinical efficacy is unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • Critical mechanistic gaps remain: no high-resolution structure of a full-length MEKK2/3–MEK5–ERK5 ternary complex exists; the mechanism by which MEK5 regulates DNA-PK in NHEJ has not been reconstituted biochemically; the mitochondrial targets for MEK5–ERK5-dependent basal mitophagy are unknown; and the kinase-independent scaffolding functions of nuclear MEK5 are poorly characterized.
  • Full-length ternary complex structure
  • Biochemical reconstitution of MEK5-to-DNA-PK signaling
  • Identity of mitochondrial degradation substrate/receptor
  • Kinase-independent nuclear functions of MEK5

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 4 GO:0016740 transferase activity 2
Localization
GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 7 R-HSA-1266738 Developmental Biology 3 R-HSA-5357801 Programmed Cell Death 2 R-HSA-1430728 Metabolism 1 R-HSA-1640170 Cell Cycle 1 R-HSA-168256 Immune System 1 R-HSA-73894 DNA Repair 1
Partners
BIRC2MAP3K2MAP3K3MAPK7PRKCIPRKCZXIAP
Complex memberships
MEKK2–MEK5–ERK5MEKK3–MEK5–ERK5

Evidence

Reading pass · 42 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 MEK5 was identified as a novel MEK family member that does not phosphorylate ERK1, ERK2, ERK3, JNK/SAPK, or p38, nor is it phosphorylated by Raf-1, c-Mos, or MEKK1, indicating it lies in a distinct MAP kinase pathway. Alternative splicing produces a 50-kDa alpha isoform (expressed in liver and brain, particulate) and a 40-kDa beta isoform (ubiquitously distributed, primarily cytosolic), with differential subcellular localization determined by a 23-amino-acid N-terminal domain in MEK5α. PCR cloning, substrate phosphorylation assays in vitro, subcellular fractionation, tissue distribution analysis The Journal of biological chemistry High 7499418
1999 MEKK3 physically interacts with MEK5 (identified by yeast two-hybrid and confirmed by co-immunoprecipitation in mammalian cells), and a dominant-active MEKK3 stimulates BMK1/ERK5 activity through MEK5; MEKK3 kinase activity is required for growth-factor-mediated activation of endogenous BMK1. Yeast two-hybrid screen, co-immunoprecipitation, dominant-active/kinase-dead mutant expression The Journal of biological chemistry High 10593883
1999 The ERK5/MEK5 pathway is required for Raf-dependent cellular transformation; constitutively active MEK5 (MEK5DD) synergizes with Raf to transform NIH 3T3 cells. Endogenous Raf-1 binds specifically to endogenous ERK5 (not ERK2 or SAPK), and Raf-1 contributes to Ras activation of ERK5 through protein-protein interactions rather than catalytic activity. Co-immunoprecipitation, NIH 3T3 transformation assay, dominant-negative and constitutively active MEK5 mutants The Journal of biological chemistry High 10531364
2000 MEKK2 binds MEK5 via yeast two-hybrid and co-immunoprecipitation, activates BMK1/ERK5 through MEK5, and does so to a greater extent than MEKK3. A dominant-negative MEK5 specifically blocks MEKK2-induced BMK1/ERK5 activation without affecting JNK, establishing MEK5 as a specific downstream effector of MEKK2 in the BMK1/ERK5 pathway. Yeast two-hybrid, co-immunoprecipitation, dominant-negative MEK5, kinase assays The Journal of biological chemistry High 11073940
2001 Constitutively active MEK5 in cardiomyocytes induces serial sarcomere assembly and an elongated hypertrophic morphology, and dominant-negative MEK5 specifically blocks LIF-induced elongation. Cardiac-specific expression of activated MEK5 in transgenic mice causes eccentric cardiac hypertrophy progressing to dilated cardiomyopathy and sudden death, establishing MEK5-ERK5 as the pathway mediating cytokine-induced serial sarcomere assembly. Adenoviral expression of CA/DN MEK5 in cardiomyocytes, transgenic mice, morphological analysis The EMBO journal High 11387209
2001 Atypical protein kinase C isoforms (aPKCs, zetaPKC and lambda/iotaPKC) interact with MEK5 in an EGF-inducible manner, and this interaction is required and sufficient for MEK5 activation in response to EGF. aPKCs activate the Jun promoter through the MEF2C element (an ERK5 target) via MEK5. Co-immunoprecipitation, dominant-negative and constitutively active constructs, reporter assays Molecular and cellular biology Medium 11158308
2003 The PB1 domains of MEKK2 and MEKK3 heterodimerize with the PB1 domain of MEK5 (but not with each other) both in vitro and in vivo. Deletion or mutation of the MEKK2 PB1 domain abolishes MEKK2-MEK5 complexes, and expression of the free MEKK2 or MEKK3 PB1 domain specifically inhibits ERK5 activation without affecting p38 or JNK pathways. In vitro PB1 domain binding, co-immunoprecipitation, mutagenesis, dominant-interference PB1 domain expression The Journal of biological chemistry High 12912994
2003 Activation of the MEK5-ERK5 pathway causes phosphorylation and stabilization of c-Fos and Fra-1. ERK5 directly phosphorylates c-Fos at sites distinct from ERK1/2 phosphorylation sites, and the C-terminal half of ERK5 is necessary for maximal transactivation of c-Fos and Fra-1. Constitutively active MEK5, phosphorylation assays, transactivation reporter assays, truncation mutants of ERK5 Genes to cells : devoted to molecular & cellular mechanisms Medium 12622723
2003 MEK5 overexpression in prostate cancer cells stimulates proliferation, motility, and invasion, markedly increases MMP-9 (but not MMP-2) mRNA expression, and activates AP-1 (but not NF-κB) transcription via the MMP-9 promoter, establishing MEK5 as an upstream regulator of MMP-9/AP-1 in prostate cancer invasion. MEK5 transfection, luciferase reporter assays, EMSA, invasion assays Oncogene Medium 12618764
2004 Endogenous MEK5 and ERK5 are localized predominantly in the nucleus in both resting and EGF-stimulated HeLa and Rat-1 cells, bound to detergent-resistant nuclear moieties, whereas their upstream activator MEKK2 is cytosolic at rest and translocates to the nucleus upon EGF stimulation. Immunofluorescence microscopy, in situ detergent extraction (NP-40), subcellular fractionation Journal of cell science High 15075238
2004 The NMR structure of the PKCiota PB1 domain reveals it adopts a ubiquitin fold with an OPCA motif forming an acidic surface that mediates interaction with the basic surface of target PB1 domains including MEK5, confirmed by mutational analysis. NMR structure determination, mutational analysis of protein-protein interaction The Journal of biological chemistry High 15143057
2004 CT-1-induced cardiac hypertrophy is mediated by the MEK5-ERK5 pathway: dominant-negative MEK5 suppresses CT-1-induced hypertrophy (protein synthesis, BNP secretion, cell surface area increase) while dominant-negative MEK1 does not, and CT-1 activates ERK5 phosphorylation that is blocked by SOCS1/3 overexpression. Adenoviral dominant-negative MEK5/MEK1, SOCS overexpression, phosphorylation assays, hypertrophy markers Journal of molecular and cellular cardiology Medium 15623437
2005 Targeted deletion of mek5 in mice results in embryonic lethality at ~E10.5 with abnormal cardiac development, decreased proliferation and increased apoptosis. In mek5-/- MEFs, MEK5 is required for ERK5 activation and for MEF2 transcriptional activity; MEK5 loss sensitizes cells to sorbitol-induced caspase-3 activation without affecting cell cycle progression. Knockout mice, MEF analysis, ERK5 kinase assays, caspase activity assays, MEF2 reporter assays Molecular and cellular biology High 15601854
2005 The MEK5-ERK5 cascade is activated in biliary epithelial cells of polycystic kidney (PCK) rats, driving aberrant proliferation; siRNA knockdown of MEK5 significantly inhibits this hyperproliferation, while MEK1/2 inhibitors (PD98059, U0126) are less effective, establishing MEK5-ERK5 as the primary proliferative pathway in biliary dysgenesis. siRNA knockdown, kinase phosphorylation assays, proliferation assays, pharmacological inhibitors The American journal of pathology Medium 15631999
2005 In Xenopus, MEK5-ERK5 is required for neural differentiation downstream of SoxD and upstream of Xngnr1 (a proneural gene); morpholino knockdown of ERK5 or MEK5 reduces head structure and inhibits neural differentiation, and forced MEK5-ERK5 activation alone is sufficient to induce neural differentiation. Morpholino antisense knockdown, constitutively active MEK5 expression, in vivo Xenopus assays EMBO reports High 16179948
2007 MEKK2 and MEK5 PB1 domains form a front-to-back heterodimer via basic (MEKK2) and acidic (MEK5) surfaces; a C-terminal 34-amino-acid extension of the MEK5 PB1 domain encodes an ERK5 docking site required for MEK5 activation of ERK5. MEKK2 in its quiescent state preferentially binds MEK5; upon activation, MEKK2 also binds MKK7 via the acidic cluster of its PB1 domain to activate JNK. Domain interaction mapping, mutagenesis, co-immunoprecipitation, kinase assays Molecular and cellular biology High 17452462
2007 NMR solution structure of MEKK3 PB1 domain reveals a ubiquitin fold with cis/trans prolyl isomerization at Gln38-Pro39; MEKK3 PB1 binds MEK5 PB1 with Kd ~10^-8 M, with Lys7 and Arg5 of the basic cluster being critical for MEK5 PB1 interaction. NMR structure determination, backbone dynamics, mutagenesis, binding affinity measurement Biochemistry High 17985933
2008 Constitutively active MEK5α inhibits ERK5 SUMOylation (at K6/K22) independently of its kinase activity but dependent on MEK5-ERK5 physical association, thereby preventing Ubc9/PIAS1-mediated SUMOylation that suppresses ERK5 transcriptional activity; H2O2 and high glucose induce ERK5 SUMOylation and reduce its transcriptional activity. CA-MEK5α transgenic mice, SUMOylation-site mutants (K6R/K22R), siRNA-PIAS1, DN-Ubc9, cardiac function assays Circulation research High 18467627
2008 Pharmacological inhibitors BIX02188 and BIX02189 inhibit purified MEK5 enzymatic activity and selectively block ERK5 phosphorylation without affecting ERK1/2 phosphorylation in sorbitol-stimulated cells; they also inhibit MEF2C transcriptional activation downstream of MEK5/ERK5. In vitro kinase assay with purified MEK5, cell-based ERK5/ERK1/2 phosphorylation assays, MEF2C reporter assay Biochemical and biophysical research communications High 18834865
2008 MEK5-BMK1 (ERK5), but not MEK1-ERK1/2, mediates fluid shear stress inhibition of TNF-induced JNK activation in endothelial cells; selective MEK5 inhibitor BIX02188 completely reverses flow-mediated inhibition of JNK, while MEK1/2-selective concentrations of PD184352 have no effect. Pharmacological inhibitors at selective concentrations, shear stress apparatus, JNK activation assays Biochemical and biophysical research communications Medium 18358237
2008 MEK5/ERK5 activation promotes an epithelial-to-mesenchymal transition (EMT) phenotype in breast cancer cells, with upregulation of vimentin, SNAI2 (slug), ZEB1, and N-cadherin, and downregulation of E-cadherin and keratins; shRNA targeting ERK5 reverses MEK5-mediated EMT gene expression. MEK5 overexpression, proteomics (2D-gel/LC-MS/MS), ERK5 shRNA knockdown, immunofluorescence Breast cancer research : BCR Medium 19087274
2008 MEK5-ERK5 regulates thymocyte apoptosis but not positive selection; retroviral dominant-negative MEK5 in developing thymocytes increases apoptosis while constitutively active MEK5 reduces it; ERK5 activity correlates with Nur77 family member levels (but not Bim) as effectors of thymocyte apoptosis. Retroviral expression of DN/CA MEK5 in thymocytes, apoptosis assays, Nur77/Bim expression analysis The EMBO journal Medium 18548009
2009 MEK5/ERK5 signaling downstream of VEGF induces Id1 and suppresses thrombospondin-1 (TSP1) expression to promote angiogenesis; Epac/Rap1 antagonizes this by suppressing Id1 and inducing TSP1, establishing MEK5 as a pro-angiogenic component controlling Id1/TSP1 balance. MEK5 knockdown/overexpression, TSP1 and Id1 expression assays, in vivo angiogenesis assay, Epac/Rap1 activation Blood Medium 19710505
2009 Constitutive MEK5/ERK5 activation strongly inhibits endothelial cell migration and increases focal contact number and size via decreased expression of p130Cas (a key regulator of focal contact turnover); this results in increased cell rigidity and reduced motility. Retroviral CA-MEK5 expression, migration assays, focal contact imaging, p130Cas expression analysis The Journal of biological chemistry Medium 19605361
2009 MEK5 and ERK5 are required for the pro-myogenic actions of IGF-2; dominant-negative MEK5 blocks IGF-2-induced myogenesis and dominant-negative ERK5 prevents nuclear localization of ERK5-GFP upon MEK5 activation; constitutively active MEK5 rescues defects caused by antisense Igf2. CA/DN MEK5 expression, ERK5-GFP live imaging, kinase activity assays, myogenic reporter assays Journal of cell science Medium 19654213
2011 MEK5 is activated by laminar shear stress in human dermal microvascular endothelial cells, activates ERK5, and induces KLF4 expression (in an ERK5-dependent manner); MEK5/ERK5/KLF4 signaling reduces endothelial inflammatory responses to TNF, in part mediated by KLF4. Laminar shear stress, constitutively active MEK5 expression, siRNA knockdown of ERK5 and KLF4, Western blotting, microarray Microcirculation (New York, N.Y. : 1994) Medium 21166929
2014 XIAP directly interacts with MEKK2/3 and competes with PB1 domain-mediated binding to MEK5. XIAP and cIAP1 conjugate predominantly K63-linked ubiquitin chains to MEKK2 and MEKK3, which directly impedes MEK5-ERK5 interaction in a trimeric complex, leading to ERK5 inactivation; loss of XIAP or cIAP1 causes ERK5 hyperactivation and promotes myoblast differentiation via MEKK2/3-ERK5. Co-immunoprecipitation, ubiquitination assays, ubiquitin linkage analysis, XIAP/cIAP1 knockdown/knockout, myoblast differentiation assay The EMBO journal High 24975362
2014 miR-143 directly represses MAP2K5 mRNA, modulating MAP2K5-ERK5 signaling during adipogenic differentiation of adipose-derived stromal cells; the stage-specific effect of miR-143 on adipogenesis is dependent on MAP2K5 suppression. miRNA overexpression, luciferase reporter assay for direct targeting, knockdown/overexpression of MAP2K5 Scientific reports Medium 24448661
2017 YAP promotes myogenic differentiation via MEK5-ERK5 by activating the Abl/Src/MEKK3/MEK5/ERK5 cascade; co-immunoprecipitation shows YAP interacts with MEKK3 and ERK5; site-directed mutagenesis of MEKK3 Y181F (disrupting the PPGY/YAP interaction motif) inhibits MEK5/ERK5 activation and myogenic differentiation. Co-immunoprecipitation, constitutively active MEK5 expression, site-directed mutagenesis, inhibitor studies, myogenic differentiation assays FASEB journal Medium 28356344
2018 MAP2K5 variants A321T and M367T (located in the kinase domain) consistently phosphorylate ERK5 at Ser731+Thr733 or Ser496, promoting ERK5 nuclear translocation and altering downstream gene expression, resulting in thyroid epithelial cell malignant transformation. Functional study of kinase domain variants, ERK5 phosphorylation assays, nuclear translocation assays, cell transformation assays International journal of cancer Medium 30132833
2018 KRAS suppression-induced MYC degradation is antagonized by an ERK1/2-inhibition-induced feedforward mechanism involving EGFR and SRC leading to ERK5 (via MEK5) activation and phosphorylation of MYC at S62, preventing its degradation; concurrent ERK1/2 and ERK5 inhibition causes synergistic MYC loss and PDAC growth suppression. Kinome-wide proteomics screen, high-throughput MYC degradation screen, ERK5/MEK5 inhibitors, phospho-MYC S62 assays, PDAC cell growth assays Cancer cell High 30423298
2019 Resistance to ERK inhibitors (SCH772984) and BRAF/MEK inhibitors in melanoma involves activation of the IGF1R-MEK5-ERK5 signaling pathway, which counteracts inhibition of ERK1/2 activation; IGF1R inhibition blocks ERK5 activation in resistant cells and reduces growth in 3D spheroids and in vivo. Drug-resistant cell line generation, ERK5/ERK1/2 phosphorylation assays, IGF1R inhibition, 3D spheroid assays, xenograft models Cancer research Medium 30833419
2019 MEK5 knockdown in prostate cancer cells impairs phosphorylation of the catalytic subunit of DNA-PK at Ser2056 in response to ionizing radiation or etoposide, delays resolution of γH2AX and 53BP1 foci, and compromises nonhomologous end joining (NHEJ) repair, sensitizing cells to genotoxic stress. MEK5 siRNA knockdown, DNA-PK phosphorylation assays, γH2AX/53BP1 foci imaging, NHEJ cell-based assay, clonogenic survival, xenograft experiments Oncogene High 31980741
2020 The MEK5-ERK5 axis controls lipid metabolism in small-cell lung cancer, including the mevalonate/cholesterol synthesis pathway; depletion of MEK5/ERK5 perturbs lipid metabolism pathways and sensitizes SCLC cells to statin treatment. MEK5/ERK5 knockdown, transcriptomics, lipidomics, pharmacological inhibition, in vitro and in vivo growth assays Cancer research Medium 31969375
2020 MEK5/ERK5 signaling mediates IL-4-induced M2 macrophage differentiation through regulation of c-Myc expression; ERK5 activation is required for M2 marker induction (Arg-1, Ym-1, Fizz-1) via c-Myc, independently of STAT3 or STAT6 phosphorylation, confirmed by myeloid-specific Erk5 knockout mice. MEK5 inhibitor, ERK5 inhibitor, myeloid-specific Erk5 conditional knockout (LysMcre/Erk5f/f), STAT3/6 phosphorylation assays, c-Myc expression analysis Journal of leukocyte biology High 32745297
2020 The MEKK3-MEK5-ERK5 kinase cascade is required for basal mitochondrial degradation (independent of exogenous damage); genetic or pharmacological inhibition of MEK5 or ERK5 increases mitochondrial content by reducing lysosome-mediated mitochondrial degradation, without affecting bulk autophagy, PINK1-Parkin mitophagy, or mitochondrial biogenesis. Genetic inhibition (CRISPR/knockout), pharmacological inhibitors, mitochondrial content quantification, lysosome-mediated degradation assays Cell death discovery Medium 33101709
2021 MEK5 inhibition in neuronal cells reduces p62 levels and increases LC3-II/LC3-I ratio (autophagy activation) in an mTOR- and ERK5-independent manner; MEK5 inhibition alleviates TDP-43 mislocalization and cell death in TDP-43-expressing neuronal cells, identifying MEK5 as a novel autophagy modulator. MEK5 inhibitor (BIX02188), autophagy markers (p62, LC3), mTOR assays, TDP-43 localization imaging Biochemical and biophysical research communications Medium 31005259
2021 The Hedgehog-GLI pathway regulates MEK5 and ERK5 expression in melanoma: GLI1 binds a non-canonical GLI consensus sequence at the MAPK7 (ERK5) promoter (confirmed by chromatin immunoprecipitation), and ERK5 is required for Hedgehog-GLI-dependent melanoma cell proliferation. Chromatin immunoprecipitation, GLI1 genetic inhibition (Patched-1 knockdown), ERK5 inhibition, proliferation assays International journal of molecular sciences Medium 34681917
2021 Map2k5 knockout mice display dopaminergic cell loss and decreased tyrosine hydroxylase in the nigrostriatal pathway, with behavioral phenotypes including decreased locomotion, coordination defects, and impaired prepulse inhibition, establishing MAP2K5 as a regulator of dopaminergic neuron survival in vivo. Targeted Map2k5 knockout mouse model, behavioral testing, immunohistochemistry for tyrosine hydroxylase Frontiers in aging neuroscience Medium 34168549
2025 MEK5-ERK5 activates the Hedgehog-GLI signaling pathway in melanoma: constitutively active MEK5 (MEK5DD) potentiates GLI transcriptional activity and increases GLI1/GLI2 protein levels; ERK5 silencing reduces GLI1/GLI2 mRNA and protein and inhibits GLI transcriptional activity; combined GLI and MEK5 inhibitors more effectively reduce melanoma spheroid growth. ERK5 shRNA, MEK5/ERK5 pharmacological inhibitors (JWG-071, AX15836, GW284543, BIX02189), MEK5DD overexpression, GLI luciferase reporter assay, 3D spheroid assays Cellular oncology Medium 39998753
2025 MAPKi/ERK5i co-inhibition in NRAS-mutant melanoma induces sustained G1 cell cycle arrest by suppressing Cyclin D1 and CDK4; forced expression of Cyclin D1 and CDK4 rescues cell cycle progression, identifying Cyclin D/CDK4 as the key mediators of the combined MEKi/ERK5i anti-proliferative effect. Transcriptome analysis, MEKi/ERK5i pharmacological inhibitors, Cyclin D1/CDK4 forced expression rescue, cell cycle analysis Cell death & disease Medium 41053077
2025 RBM39 (a splicing factor) maintains full-length MEK5 mRNA splicing; RBM39 knockdown causes mis-splicing of MEK5, generating aberrant isoforms with exon loss that lack kinase function and undergo proteasomal degradation, thereby inhibiting MM cell survival. Full-length MEK5 activity maintains MM cell survival via p65/NF-κB. RBM39 knockdown, indisulam-mediated RBM39 degradation, splicing analysis, MEK5 isoform characterization, proteasome inhibition, p65 activity assays Blood advances Medium 40048740

Source papers

Stage 0 corpus · 91 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy. The EMBO journal 233 11387209
1995 Isolation of MEK5 and differential expression of alternatively spliced forms. The Journal of biological chemistry 186 7499418
2011 MEK5/ERK5 pathway: the first fifteen years. Biochimica et biophysica acta 160 22020294
1999 MEKK3 directly regulates MEK5 activity as part of the big mitogen-activated protein kinase 1 (BMK1) signaling pathway. The Journal of biological chemistry 160 10593883
2018 KRAS Suppression-Induced Degradation of MYC Is Antagonized by a MEK5-ERK5 Compensatory Mechanism. Cancer cell 155 30423298
2003 MEK5 overexpression is associated with metastatic prostate cancer, and stimulates proliferation, MMP-9 expression and invasion. Oncogene 146 12618764
2008 Identification of pharmacological inhibitors of the MEK5/ERK5 pathway. Biochemical and biophysical research communications 137 18834865
2018 Biological effects of melatonin on osteoblast/osteoclast cocultures, bone, and quality of life: Implications of a role for MT2 melatonin receptors, MEK1/2, and MEK5 in melatonin-mediated osteoblastogenesis. Journal of pineal research 132 29285799
2000 MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway. The Journal of biological chemistry 122 11073940
1999 Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control. The Journal of biological chemistry 109 10531364
2005 Targeted deletion of mek5 causes early embryonic death and defects in the extracellular signal-regulated kinase 5/myocyte enhancer factor 2 cell survival pathway. Molecular and cellular biology 108 15601854
2003 Regulation of c-Fos and Fra-1 by the MEK5-ERK5 pathway. Genes to cells : devoted to molecular & cellular mechanisms 90 12622723
2017 Oncogenic signaling of MEK5-ERK5. Cancer letters 86 28153789
2008 Proteomic analysis of tumor necrosis factor-alpha resistant human breast cancer cells reveals a MEK5/Erk5-mediated epithelial-mesenchymal transition phenotype. Breast cancer research : BCR 82 19087274
2014 MicroRNA-143 regulates adipogenesis by modulating the MAP2K5-ERK5 signaling. Scientific reports 79 24448661
2003 PB1 domains of MEKK2 and MEKK3 interact with the MEK5 PB1 domain for activation of the ERK5 pathway. The Journal of biological chemistry 78 12912994
2008 Effects of MEK5/ERK5 association on small ubiquitin-related modification of ERK5: implications for diabetic ventricular dysfunction after myocardial infarction. Circulation research 74 18467627
2011 MEK5 is activated by shear stress, activates ERK5 and induces KLF4 to modulate TNF responses in human dermal microvascular endothelial cells. Microcirculation (New York, N.Y. : 1994) 64 21166929
2004 Solution structure of atypical protein kinase C PB1 domain and its mode of interaction with ZIP/p62 and MEK5. The Journal of biological chemistry 64 15143057
2016 The MEK5/ERK5 signalling pathway in cancer: a promising novel therapeutic target. Drug discovery today 63 27320690
2001 MEK5, a new target of the atypical protein kinase C isoforms in mitogenic signaling. Molecular and cellular biology 61 11158308
2021 The MEK5/ERK5 Pathway in Health and Disease. International journal of molecular sciences 59 34299213
2020 The MEK5-ERK5 Kinase Axis Controls Lipid Metabolism in Small-Cell Lung Cancer. Cancer research 59 31969375
2007 HGF mediates cell proliferation of human mesothelioma cells through a PI3K/MEK5/Fra-1 pathway. American journal of respiratory cell and molecular biology 58 17872495
2004 MEK5 and ERK5 are localized in the nuclei of resting as well as stimulated cells, while MEKK2 translocates from the cytosol to the nucleus upon stimulation. Journal of cell science 56 15075238
2015 SATB2 suppresses the progression of colorectal cancer cells via inactivation of MEK5/ERK5 signaling. The FEBS journal 55 25662172
2004 Hypertrophic responses to cardiotrophin-1 are not mediated by STAT3, but via a MEK5-ERK5 pathway in cultured cardiomyocytes. Journal of molecular and cellular cardiology 50 15623435
2005 Activation of the MEK5/ERK5 cascade is responsible for biliary dysgenesis in a rat model of Caroli's disease. The American journal of pathology 47 15631999
2019 Resistance to MAPK Inhibitors in Melanoma Involves Activation of the IGF1R-MEK5-Erk5 Pathway. Cancer research 46 30833419
2018 A kinome-wide high-content siRNA screen identifies MEK5-ERK5 signaling as critical for breast cancer cell EMT and metastasis. Oncogene 46 29713055
2016 MEK5/ERK5 signaling inhibition increases colon cancer cell sensitivity to 5-fluorouracil through a p53-dependent mechanism. Oncotarget 46 27144434
2015 Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation. Cell death & disease 43 25855966
2009 A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis. Blood 43 19710505
2004 Stat3 upregulates MEK5 expression in human breast cancer cells. Oncogene 43 15378007
2020 Targeted Avenues for Cancer Treatment: The MEK5-ERK5 Signaling Pathway. Trends in molecular medicine 40 32277933
2019 MEK5/ERK5 activation regulates colon cancer stem-like cell properties. Cell death discovery 39 30774996
2018 Whole exome and target sequencing identifies MAP2K5 as novel susceptibility gene for familial non-medullary thyroid carcinoma. International journal of cancer 37 30132833
2015 Genetic variations in SEC16B, MC4R, MAP2K5 and KCTD15 were associated with childhood obesity and interacted with dietary behaviors in Chinese school-age population. Gene 37 25637721
2013 MEK5/ERK5 signaling suppresses estrogen receptor expression and promotes hormone-independent tumorigenesis. PloS one 37 23950888
2008 Fluid shear stress inhibits TNF-mediated JNK activation via MEK5-BMK1 in endothelial cells. Biochemical and biophysical research communications 36 18358237
2008 Non-redundant function of the MEK5-ERK5 pathway in thymocyte apoptosis. The EMBO journal 36 18548009
2005 Requirement of the MEK5-ERK5 pathway for neural differentiation in Xenopus embryonic development. EMBO reports 36 16179948
2016 Upregulation of MEK5 by Stat3 promotes breast cancer cell invasion and metastasis. Oncology reports 33 27878304
2004 Characterization of the MEK5-ERK5 module in human neutrophils and its relationship to ERK1/ERK2 in the chemotactic response. The Journal of biological chemistry 31 15381709
2020 MEK5/ERK5 signaling mediates IL-4-induced M2 macrophage differentiation through regulation of c-Myc expression. Journal of leukocyte biology 30 32745297
2009 MEK5/ERK5 signaling modulates endothelial cell migration and focal contact turnover. The Journal of biological chemistry 30 19605361
2017 YAP promotes myogenic differentiation via the MEK5-ERK5 pathway. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 29 28356344
2009 MEK5 and ERK5 are mediators of the pro-myogenic actions of IGF-2. Journal of cell science 28 19654213
2014 Ubiquitin-dependent regulation of MEKK2/3-MEK5-ERK5 signaling module by XIAP and cIAP1. The EMBO journal 27 24975362
2011 Inhibition of MEK5 by BIX02188 induces apoptosis in cells expressing the oncogenic mutant FLT3-ITD. Biochemical and biophysical research communications 25 21820407
2012 Expression of the phosphorylated MEK5 protein is associated with TNM staging of colorectal cancer. BMC cancer 22 22458985
2014 The MEK5/ERK5 pathway mediates fluid shear stress promoted osteoblast differentiation. Connective tissue research 21 24111522
2019 Pharmacological inhibition of the MEK5/ERK5 and PI3K/Akt signaling pathways synergistically reduces viability in triple-negative breast cancer. Journal of cellular biochemistry 20 31464004
2007 Noncanonical function of MEKK2 and MEK5 PB1 domains for coordinated extracellular signal-regulated kinase 5 and c-Jun N-terminal kinase signaling. Molecular and cellular biology 20 17452462
2018 The MEK5/ERK5 mitogen-activated protein kinase cascade is an effector pathway of bone-sustaining bisphosphonates that regulates osteogenic differentiation and mineralization. Bone 19 29567200
2007 Insight into the binding properties of MEKK3 PB1 to MEK5 PB1 from its solution structure. Biochemistry 19 17985933
2014 The effects of a MAP2K5 microRNA target site SNP on risk for anxiety and depressive disorders. American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics 18 24436253
2018 Moderate Fluid Shear Stress Could Regulate the Cytoskeleton of Nucleus Pulposus and Surrounding Inflammatory Mediators by Activating the FAK-MEK5-ERK5-cFos-AP1 Signaling Pathway. Disease markers 16 30008976
2021 Inhibition of MEK5/ERK5 signaling overcomes acquired resistance to the third generation EGFR inhibitor, osimertinib, via enhancing Bim-dependent apoptosis. Cancer letters 15 34245854
2021 The Hedgehog-GLI Pathway Regulates MEK5-ERK5 Expression and Activation in Melanoma Cells. International journal of molecular sciences 15 34681917
2017 Yeast genetic interaction screen of human genes associated with amyotrophic lateral sclerosis: identification of MAP2K5 kinase as a potential drug target. Genome research 14 28596290
2023 MEK5-ERK5 Axis Promotes Self-renewal and Tumorigenicity of Glioma Stem Cells. Cancer research communications 13 36968222
2023 Pathophysiological Impact of the MEK5/ERK5 Pathway in Oxidative Stress. Cells 13 37190064
2022 The role of MEK1/2 and MEK5 in melatonin-mediated actions on osteoblastogenesis, osteoclastogenesis, bone microarchitecture, biomechanics, and bone formation. Journal of pineal research 13 35674448
2021 Activation of the BABA-induced priming defence through redox homeostasis and the modules of TGA1 and MAPKK5 in postharvest peach fruit. Molecular plant pathology 13 34498365
2020 Targeting MEK5 impairs nonhomologous end-joining repair and sensitizes prostate cancer to DNA damaging agents. Oncogene 13 31980741
2020 Involvement of MEK5/ERK5 signaling pathway in manganese-induced cell injury in dopaminergic MN9D cells. Journal of trace elements in medicine and biology : organ of the Society for Minerals and Trace Elements (GMS) 13 32480051
2019 Inhibition of MEK5 suppresses TDP-43 toxicity via the mTOR-independent activation of the autophagy-lysosome pathway. Biochemical and biophysical research communications 13 31005259
2012 REST and its downstream molecule Mek5 regulate survival of primordial germ cells. Developmental biology 13 23022299
2019 MEK5 promotes lung adenocarcinoma. The European respiratory journal 12 30442718
2019 ERK5 negatively regulates Kruppel-like factor 4 and promotes osteogenic lineage cell proliferation in response to MEK5 overexpression or fluid shear stress. Connective tissue research 12 31749391
2015 MEK5 suppresses osteoblastic differentiation. Biochemical and biophysical research communications 11 25998381
2011 MEK5/ERK5/mef2: a novel signaling pathway affected by hepatitis C virus non-enveloped capsid-like particles. Biochimica et biophysica acta 11 21767578
2021 Dual inhibition of MEK1/2 and MEK5 suppresses the EMT/migration axis in triple-negative breast cancer through FRA-1 regulation. Journal of cellular biochemistry 10 33876843
2019 Biochanin A protects against PM2.5-induced acute pulmonary cell injury by interacting with the target protein MEK5. Food & function 10 31608342
2016 MEK5 overexpression is associated with the occurrence and development of colorectal cancer. BMC cancer 8 27160304
2021 Map2k5-Deficient Mice Manifest Phenotypes and Pathological Changes of Dopamine Deficiency in the Central Nervous System. Frontiers in aging neuroscience 7 34168549
2020 MEKK3-MEK5-ERK5 signaling promotes mitochondrial degradation. Cell death discovery 7 33101709
2018 Haplotype Association of the MAP2K5 Gene with Antipsychotics-Induced Symptoms of Restless Legs Syndrome among Patients with Schizophrenia. Psychiatry investigation 5 29422930
2023 Potentially functional genetic variants in RPS6KA4 and MAP2K5 in the MAPK signaling pathway predict HBV-related hepatocellular carcinoma survival. Molecular carcinogenesis 4 37278562
2024 A network-based drug prioritization and combination analysis for the MEK5/ERK5 pathway in breast cancer. BioData mining 3 38378612
2022 Fine Mapping of the MAP2K5 Region Identified rs7175517 as a Causal Variant Related to BMI in China and the United Kingdom Populations. Frontiers in genetics 3 35368675
2021 Constitutive activation of MEK5 promotes a mesenchymal and migratory cell phenotype in triple negative breast cancer. Oncoscience 3 34026925
2025 The MEK5/ERK5 pathway promotes the activation of the Hedgehog/GLI signaling in melanoma cells. Cellular oncology (Dordrecht, Netherlands) 2 39998753
2025 MEK5/ERK5 inhibition sensitizes NRAS-mutant melanoma to MAPK-targeted therapy by preventing Cyclin D/CDK4-mediated G1/S progression. Cell death & disease 2 41053077
2022 Aberrant MEK5 signalling promotes clear cell renal cell carcinoma development via mTOR activation. Journal of cancer research and clinical oncology 2 35713705
2025 Targeting the RBM39-MEK5 axis synergizes with bortezomib to inhibit the malignant growth of multiple myeloma. Blood advances 1 40048740
2025 MEK5-ERK5 pathway mediates mitophagy by regulating Nur77 to promote tumorigenesis of osteosarcoma cells. European journal of medical research 0 39972514
2025 PER1 Serves as a Tumor Suppressor in Breast Cancer by Regulating MEK5/ERK5 Signaling Pathway. International journal of general medicine 0 40809954
2025 MT@SiO2 Enhances MEK5-MAPK6-NAC32 Mediated Salicylic Acid Synthesis Which Increases Resistance to Glomerella Leaf Spot in Apple. Plant biotechnology journal 0 41386701
2018 Corrigendum to "Moderate Fluid Shear Stress Could Regulate the Cytoskeleton of Nucleus Pulposus and Surrounding Inflammatory Mediators by Activating the FAK-MEK5-ERK5-cFos-AP1 Signaling Pathway". Disease markers 0 30363744