Affinage

MAP2K5

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

Length
448 aa
Mass
50.1 kDa
Annotated
2026-06-10
91 papers in source corpus 40 papers cited in narrative 40 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/7 claims corpus-supported (86%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAP2K5 (MEK5) is a dual-specificity MAP kinase kinase that defines a distinct MAP kinase pathway, functioning as the obligate and specific upstream activator of ERK5/BMK1 without acting on ERK1/2, JNK, or p38 (PMID:7499418, PMID:15601854). It is recruited and activated by the upstream kinases MEKK2 and MEKK3 through PB1 domain-mediated, front-to-back heterodimerization in which a basic cluster on the MEKK PB1 face engages an acidic surface on the MEK5 PB1 domain, an interaction required for ERK5 activation; a C-terminal extension of the MEK5 PB1 domain serves as the ERK5 docking site, organizing a MEKK3-MEK5-ERK5 trimeric module (PMID:12912994, PMID:17452462, PMID:17985933). MEK5 is alternatively activated by atypical PKC isoforms downstream of EGF and integrates growth-factor, shear-stress, and YAP/Abl/Src inputs into the cascade (PMID:11158308, PMID:21166929, PMID:28356344). Beyond its catalytic role, MEK5 physically binds ERK5 and prevents its repressive SUMOylation independently of kinase activity, thereby maintaining ERK5 transcriptional output (PMID:18467627). The pathway is restrained by XIAP/cIAP1, which conjugate K63-linked ubiquitin to MEKK2/3 to disrupt the trimeric complex (PMID:24975362). Through ERK5, MEK5 controls transcriptional programs governing MEF2C, c-Fos/Fra-1, KLF4, Nur77, c-Myc, STAT3, and GLI1/2 (PMID:12622723, PMID:15601854, PMID:18548009, PMID:21166929, PMID:30423298, PMID:36968222, PMID:39998753), and is physiologically required for cardiac development and sarcomere assembly, embryonic survival, neural differentiation, myogenesis, thymocyte apoptosis, endothelial mechanosensing, M2 macrophage polarization, basal mitophagy, and NHEJ DNA repair (PMID:11387209, PMID:15601854, PMID:16179948, PMID:19654213, PMID:18548009, PMID:31980741, PMID:33101709, PMID:32745297). The pathway is co-opted across cancers as a proliferative, pro-metastatic, and drug-resistance route, and kinase-domain MAP2K5 variants (A321T, M367T) are linked to familial non-medullary thyroid carcinoma (PMID:30132833, PMID:30423298, PMID:30833419).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1995 High

    Established that MEK5 is a MEK-family kinase belonging to a distinct, previously uncharacterized MAP kinase pathway rather than the ERK1/2, JNK, or p38 modules, and that splicing generates isoforms with different localization.

    Evidence PCR cloning, in vitro kinase assays against multiple MAPK substrates and upstream kinases, subcellular fractionation

    PMID:7499418

    Open questions at the time
    • Downstream substrate (ERK5) not yet identified
    • Physiological upstream activators unknown
    • Functional significance of alpha/beta isoform localization untested in vivo
  2. 1999 High

    Identified MEKK2 and MEKK3 as direct upstream kinases of MEK5 and placed the module downstream of growth-factor and Ras/Raf signaling, defining the MEKK→MEK5→ERK5 cascade and its transforming potential.

    Evidence Yeast two-hybrid, reciprocal co-IP, dominant-active/negative epistasis, endogenous co-IP, NIH 3T3 transformation assays

    PMID:10531364 PMID:10593883 PMID:11073940

    Open questions at the time
    • Structural basis of MEKK-MEK5 binding not yet resolved
    • Cell-type determinants of MEKK2-vs-MEKK3 usage incompletely defined
    • Mechanism of Raf-ERK5 association unclear
  3. 2001 Medium

    Demonstrated alternative upstream input via atypical PKC downstream of EGF and established a physiological output in cardiac sarcomere assembly and hypertrophy.

    Evidence Co-IP, dominant mutants, luciferase reporters; adenoviral and cardiac-specific transgenic mouse models

    PMID:11158308 PMID:11387209

    Open questions at the time
    • aPKC phosphorylation sites on MEK5 not mapped
    • Direct vs indirect cardiac transcriptional targets not fully defined
  4. 2003 High

    Resolved the PB1 domain interaction code governing MEK5 recruitment and identified the first transcriptional effectors (c-Fos/Fra-1, AP-1) of the pathway, linking it to invasion and MMP-9.

    Evidence In vitro PB1 binding assays, co-IP, PB1 mutagenesis, transactivation/luciferase reporters, EMSA

    PMID:12618764 PMID:12622723 PMID:12912994

    Open questions at the time
    • Direct ERK5 substrates among transcription factors not all distinguished from indirect effects
    • Quantitative PB1 binding parameters not yet measured
  5. 2004 Medium

    Defined the subcellular logic of signaling, showing endogenous MEK5 and ERK5 are nuclear-anchored and that MEKK2 nuclear translocation transmits the EGF signal, and provided NMR-level structure of a PB1 partner surface.

    Evidence Immunofluorescence of endogenous proteins, NP-40 in situ fractionation; NMR structure of PKCiota PB1 with mutagenesis

    PMID:15075238 PMID:15143057

    Open questions at the time
    • Identity of nuclear anchoring moieties unknown
    • Direct MEK5 PB1 mutagenesis not tested in the structural study
  6. 2005 High

    Genetically validated MEK5 in vivo as the essential ERK5 activator and a required regulator of proliferation, survival, and cardiac development, and extended its role to neural differentiation.

    Evidence Mek5 knockout mice (E10.5 lethality), MEFs with MEF2 reporters and caspase assays; Xenopus morpholino knockdown and gain-of-function epistasis

    PMID:15601854 PMID:16179948

    Open questions at the time
    • Tissue-autonomous vs systemic requirements not separated due to embryonic lethality
    • Direct ERK5 substrates driving survival not identified
  7. 2007 High

    Defined the front-to-back PB1 binding geometry, the MEK5 PB1 C-terminal ERK5 docking site, and a competitive switch in MEKK2 partner choice, providing the quantitative structural mechanism of cascade assembly.

    Evidence PB1 mutagenesis, co-IP, kinase assays; NMR structure of MEKK3 PB1 with Kd measurement (~10^-8 M)

    PMID:17452462 PMID:17985933

    Open questions at the time
    • Full MEKK-MEK5-ERK5 ternary structure not solved
    • Regulation of the MEKK2 MKK7-vs-MEK5 switch in physiological settings unclear
  8. 2008 High

    Uncovered a kinase-independent function of MEK5 in protecting ERK5 from repressive SUMOylation, and defined pathway-specific roles in EMT and endothelial mechanosensing using selective inhibitors.

    Evidence Kinase-dead mutants, SUMOylation and PIAS1 siRNA assays, CA-MEK5alpha transgenic mice; selective MEK5 inhibitors BIX02188/BIX02189; proteomics and ERK5 shRNA epistasis

    PMID:18358237 PMID:18467627 PMID:18834865 PMID:19087274

    Open questions at the time
    • Mechanism by which MEK5 binding blocks Ubc9/PIAS1 access not structurally defined
    • EMT transcriptional targets not directly tied to ERK5 phosphorylation events
  9. 2011 Medium

    Defined non-redundant tissue-specific roles in thymocyte apoptosis (via Nur77) and endothelial KLF4 induction, distinguishing MEK5/ERK5 from ERK1/2 outputs.

    Evidence Retroviral dominant/active MEK5 in thymocytes with Nur77/Bim analysis; shear stress with ERK5/KLF4 siRNA epistasis

    PMID:18548009 PMID:21166929

    Open questions at the time
    • Direct ERK5 substrate linking to Nur77 induction not identified
    • Whether KLF4 is a direct vs indirect ERK5 target unresolved
  10. 2014 High

    Identified the negative regulatory mechanism whereby XIAP/cIAP1-mediated K63-ubiquitination of MEKK2/3 disrupts the trimeric MEK5 complex, defining how the cascade is restrained during differentiation.

    Evidence Reciprocal co-IP, K63-linkage ubiquitination assays, XIAP/cIAP1 loss-of-function, myoblast differentiation assays

    PMID:24975362

    Open questions at the time
    • Deubiquitinases reversing this mark not identified
    • Signals controlling XIAP engagement of MEKK2/3 unknown
  11. 2017 Medium

    Connected upstream YAP/Abl/Src signaling to the cascade through a MEKK3 PPGY motif, defining how mechanical/Hippo inputs feed MEK5 activation during myogenesis.

    Evidence Co-IP, MEKK3 Y181F mutagenesis, pharmacological inhibition of c-Abl/Src/MEK5, myogenesis assays

    PMID:28356344

    Open questions at the time
    • Direct vs scaffold role of YAP at the MEKK3 PB1 module unclear
    • In vivo requirement of the PPGY interaction not tested
  12. 2018 High

    Established MAP2K5 mutations as drivers of familial thyroid carcinoma and defined an ERK1/2-suppression-induced feedforward route in which MEK5/ERK5 stabilizes MYC, explaining pathway co-option in cancer and drug resistance.

    Evidence Exome sequencing and functional expression of MAP2K5 variants; kinome proteomics, MYC degradation screen, pharmacological ERK1/2+ERK5 inhibition with S62-MYC phosphorylation readout

    PMID:30132833 PMID:30423298

    Open questions at the time
    • Whether ERK5 directly phosphorylates MYC vs via a downstream kinase not fully resolved
    • Generality of MAP2K5 germline variants beyond studied families unknown
  13. 2020 High

    Broadened MEK5's physiological repertoire to basal mitophagy, M2 macrophage polarization (via c-Myc, STAT3/STAT6-independent), and lipid/mevalonate metabolism in cancer, showing pathway outputs extend beyond classical proliferation control.

    Evidence Genetic and pharmacological pathway inhibition, conditional Erk5 knockout mice, transcriptomics/lipidomics, statin synergy

    PMID:31969375 PMID:32745297 PMID:33101709

    Open questions at the time
    • Direct effectors linking ERK5 to mitophagy machinery not identified
    • Mechanism of c-Myc regulation in M2 macrophages not fully mapped
  14. 2019 High

    Revealed MEK5 functions in genome maintenance and a non-canonical autophagy role: it supports NHEJ via DNA-PK Ser2056 phosphorylation, while its inhibition activates the autophagy-lysosome pathway ERK5- and mTOR-independently.

    Evidence RNAi knockdown, gammaH2AX/53BP1 foci, DNA-PK phospho-Westerns, NHEJ assay, xenografts; MEK5 inhibitor with LC3-II/p62 and TDP-43 readouts

    PMID:31005259 PMID:31980741

    Open questions at the time
    • Whether MEK5 acts on DNA-PK directly or through ERK5 not established
    • Molecular target of the ERK5-independent autophagy effect unknown
  15. 2025 Medium

    Extended cancer-relevant outputs to Hedgehog-GLI activation, Cyclin D/CDK4-dependent cell-cycle control under combined inhibition, and RBM39-dependent MEK5 splicing required for myeloma survival, reinforcing MEK5 as a therapeutic node.

    Evidence Reciprocal ERK5/MEK5DD gain/loss-of-function, GLI and cell-cycle rescue experiments, RBM39 depletion with splice-isoform and bortezomib synergy assays

    PMID:39998753 PMID:40048740 PMID:41053077

    Open questions at the time
    • Direct ERK5 substrates linking to GLI and Cyclin D1 not defined
    • Mechanism by which RBM39 controls functional MEK5 splicing not fully mapped

Open questions

Synthesis pass · forward-looking unresolved questions
  • The complete catalogue of direct ERK5 substrates downstream of MEK5, the structural basis of the kinase-independent anti-SUMOylation function, and which physiological outputs depend on catalytic versus scaffolding activity of MEK5 remain to be resolved.
  • No ternary MEKK-MEK5-ERK5 structure
  • Direct vs ERK5-mediated effects on DNA-PK, MYC, and transcription factors unresolved
  • Catalytic vs scaffold contributions to in vivo phenotypes not dissected

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 3 GO:0140313 molecular sequestering activity 1
Localization
GO:0005634 nucleus 3 GO:0005829 cytosol 2 GO:0005856 cytoskeleton 1
Pathway
R-HSA-1266738 Developmental Biology 4 R-HSA-162582 Signal Transduction 4 R-HSA-1643685 Disease 4 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-168256 Immune System 2 R-HSA-9612973 Autophagy 2 R-HSA-73894 DNA Repair 1
Partners
MAP3K2MAP3K3MAPK7PRKCIPRKCZRAF1XIAPYAP1
Complex memberships
MEKK3-MEK5-ERK5 trimeric module

Evidence

Reading pass · 40 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 MEK5 was isolated as a novel MEK family member that does not phosphorylate ERK1, ERK2, ERK3, JNK/SAPK, or p38/HOG1, and is not highly 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/associated with actin cytoskeleton-like domain) and a 40-kDa beta isoform (ubiquitous, primarily cytosolic), with the N-terminal 23-aa exon of MEK5alpha directing differential subcellular localization. PCR cloning, in vitro kinase assays, subcellular fractionation, Northern/Western blotting 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 constitutively active MEKK3 stimulates BMK1/ERK5 activity through MEK5. Dominant-active MEKK3 is required for growth factor-mediated activation of endogenous BMK1, placing MEKK3 as a direct upstream kinase of MEK5 in the BMK1/ERK5 pathway. Yeast two-hybrid, co-immunoprecipitation, dominant-active/dominant-negative overexpression, kinase activity assays 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 (but not ERK2 or SAPK), suggesting regulatory protein-protein interactions contribute to Ras/Raf activation of ERK5. Co-immunoprecipitation of endogenous proteins, NIH 3T3 transformation assays, dominant-active MEK5 overexpression, epistasis analysis The Journal of biological chemistry High 10531364
2000 MEKK2 binds MEK5 via yeast two-hybrid and co-immunoprecipitation, and MEKK2 expression stimulates BMK1/ERK5 activity. MEKK2 activates BMK1/ERK5 to a greater extent than MEKK3 and with higher apparent affinity for MEK5. Dominant-negative MEK5 blocks MEKK2-induced BMK1/ERK5 activation without affecting JNK, demonstrating MEK5 is a specific downstream effector of MEKK2. In D10 T cells, dominant-negative MEKK2 (but not MEKK3) inhibits BMK1/ERK5, showing cell-type-specific usage of upstream kinases. Yeast two-hybrid, co-immunoprecipitation, dominant-negative/constitutively active overexpression, kinase activity assays The Journal of biological chemistry High 11073940
2001 MEK5 induces eccentric cardiac hypertrophy with serial sarcomere assembly in cardiomyocytes in vitro. Constitutively active MEK5 causes elongated cardiomyocyte morphology, and dominant-negative MEK5 specifically blocks LIF-induced cardiomyocyte elongation and fetal gene expression without blocking other LIF hypertrophic responses. Cardiac-specific transgenic expression of activated MEK5 in mice produces eccentric cardiac hypertrophy progressing to dilated cardiomyopathy and sudden death. Adenoviral overexpression of constitutively active and dominant-negative MEK5 in cardiomyocytes; cardiac-specific transgenic mice; morphological and gene expression analysis The EMBO journal High 11387209
2001 Atypical protein kinase C isoforms (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. The aPKC-MEK5 interaction depends on the aPKC interaction domain (acidic amino acid stretch) present in MEK5. aPKC activation of MEK5 leads to MEF2C-element-dependent Jun promoter activation. Co-immunoprecipitation, dominant-negative/constitutively active overexpression, luciferase reporter assays Molecular and cellular biology Medium 11158308
2003 The MEK5-ERK5 pathway phosphorylates and stabilizes c-Fos and Fra-1. Phosphorylation of c-Fos by ERK5 (and downstream kinases) occurs at sites distinct from ERK1/2-dependent sites, and MEK5-ERK5 pathway activation markedly increases c-Fos transactivation activity. The C-terminal half of ERK5 is required for maximal transactivation of c-Fos and Fra-1. Constitutively active MEK5 overexpression, phosphorylation analysis, mutagenesis of ERK5, luciferase/transactivation assays Genes to cells Medium 12622723
2003 PB1 domains of MEKK2 and MEKK3 bind the PB1 domain of MEK5 but do not significantly homo- or heterodimerize with each other in vitro. Co-immunoprecipitation confirms MEKK2-MEK5 complex formation in vivo. Deletion or mutation of the MEKK2 PB1 domain abolishes MEKK2-MEK5 interaction. Expression of free MEKK2 or MEKK3 PB1 domains inhibits ERK5 activation specifically (not p38 or JNK), demonstrating that PB1 domain-mediated association is required for MEK5 activation by MEKK2/3. In vitro PB1 domain binding assays, co-immunoprecipitation, PB1 deletion/mutation analysis, kinase activity assays The Journal of biological chemistry High 12912994
2003 MEK5 overexpression in prostate cancer cells stimulates proliferation, motility, invasion, and selectively increases MMP-9 (but not MMP-2) mRNA expression. Luciferase and EMSA assays show MEK5 activates the MMP-9 promoter via AP-1 (not NF-κB) binding sites, and MEK5 enhances AP-1 transcriptional activity approximately two-fold. MEK5 transfection, proliferation/invasion assays, RT-PCR, luciferase reporter assays, EMSA Oncogene Medium 12618764
2004 MEK5 and ERK5 are localized in the nucleus of both resting and EGF-stimulated HeLa and Rat-1 cells (endogenous proteins), where they are bound to detergent-resistant nuclear moieties. Exogenous overexpressed ERK5 localizes to the cytosol, revealing saturation of nuclear anchors by endogenous ERK5. Upon EGF stimulation, MEK5 is released from nuclear anchors but remains nuclear, while MEKK2 translocates from cytosol to nucleus, enabling signal transmission to nuclear MEK5. Immunofluorescence microscopy of endogenous proteins, in situ detergent (NP-40) extraction fractionation, EGF stimulation Journal of cell science Medium 15075238
2004 NMR structure of the PKCiota PB1 domain reveals a ubiquitin fold with an OPCA motif forming an acidic surface that interacts with the basic surface of target PB1 domains (including MEK5). Mutational analysis of the PKCiota-ZIP/p62 PB1-PB1 interaction confirms the acidic surface is critical for binding. The PKCiota PB1 domain can interact with targets via either its acidic (OPCA) surface or a conserved lysine on the opposite face. NMR structure determination, mutagenesis, PB1 domain interaction analysis The Journal of biological chemistry Medium 15143057
2005 Targeted deletion of mek5 in mice results in embryonic lethality at ~E10.5 with abnormal cardiac development, decreased proliferation, and increased apoptosis in heart, head, and dorsal regions. MEK5-deficient mouse embryonic fibroblasts show impaired ERK5 activation and reduced MEF2 transcriptional activity, and are sensitized to sorbitol-induced caspase-3 activity. MEK5 is established in vivo as the essential activator of ERK5 and a required regulator of cell survival. Targeted gene knockout in mice, phenotypic analysis, MEF2 transcriptional reporter assays, caspase-3 activity assays in MEFs Molecular and cellular biology High 15601854
2005 MEK5-ERK5 pathway activation is responsible for biliary epithelial cell hyperproliferation in PCK rats (Caroli's disease model). MEK5 is overexpressed in PCK rat biliary epithelial cells, leading to increased ERK5 phosphorylation. siRNA knockdown of MEK5 significantly inhibits the abnormal biliary cell proliferation, while MEK1/2 inhibitors (PD98059, U0126) are less effective. siRNA knockdown of MEK5, Western blotting for ERK5 phosphorylation, cell proliferation assays, pharmacological inhibitor comparison The American journal of pathology Medium 15631999
2005 MEK5-ERK5 pathway is required for neural differentiation in Xenopus embryos. Knockdown of Xenopus MEK5 or ERK5 with antisense morpholino oligonucleotides reduces head structure and inhibits neural differentiation. Forced activation of MEK5-ERK5 alone is sufficient to induce neural differentiation. MEK5-ERK5 is necessary for SoxD neuralizing activity and sufficient for expression of the proneural gene Xngnr1, placing MEK5-ERK5 downstream of SoxD and upstream of Xngnr1. Antisense morpholino knockdown in Xenopus embryos, constitutively active MEK5-ERK5 overexpression, genetic epistasis analysis EMBO reports High 16179948
2007 MEKK2 and MEK5 PB1 domains interact in a front-to-back arrangement: basic residues on the MEKK2 PB1 front bind to acidic clusters on the MEK5 PB1 back. A 34-amino-acid C-terminal extension of the MEK5 PB1 domain constitutes an ERK5 docking site required for MEK5 activation of ERK5. In quiescent cells, MEKK2 preferentially binds MEK5; upon MEKK2 activation, it switches to bind MKK7 via its PB1 acidic cluster, leading to JNK activation. PB1 domain mutagenesis, co-immunoprecipitation, kinase activation assays, domain-binding specificity analysis Molecular and cellular biology High 17452462
2007 NMR solution structure of MEKK3 PB1 domain reveals a ubiquitin fold with prolyl isomerization at Gln38-Pro39 producing two structural conformers. MEKK3 PB1 binds MEK5 PB1 with Kd ~10^-8 M. Mutagenesis identifies Lys7 and Arg5 in the MEKK3 PB1 basic cluster as critical residues for interaction with MEK5 PB1. NMR structure determination, backbone dynamics, mutagenesis, binding affinity measurement Biochemistry High 17985933
2008 Constitutively active MEK5alpha (CA-MEK5alpha) inhibits ERK5 SUMOylation independently of MEK5 kinase activity but dependently on MEK5-ERK5 physical association. H2O2 and high glucose induce ERK5 SUMOylation (mediated by E2 conjugase Ubc9 and E3 ligase PIAS1), which represses ERK5 transcriptional activity. CA-MEK5alpha transgenic mice show protection against DM-exacerbated LV dysfunction and apoptosis after MI by preventing ERK5 SUMOylation. Kinase-dead MEK5 mutants, SUMOylation assays, siRNA knockdown of PIAS1, CA-MEK5alpha transgenic mice, cardiac function measurement post-MI Circulation research High 18467627
2008 MEK5/ERK5-mediated EMT in TNF-alpha-resistant MCF-7 breast cancer cells involves upregulation of vimentin, GSTP1, CKB and EMT regulators SNAI2/ZEB1/N-cadherin, and downregulation of keratins and E-cadherin. RNA interference targeting ERK5 reverses MEK5-mediated EMT gene expression, establishing ERK5 as required downstream effector of MEK5 in this context. 2D gel proteomics, LC-MS/MS, RT-PCR, immunofluorescence, shRNA knockdown of ERK5 Breast cancer research Medium 19087274
2008 MEK5-selective inhibitor BIX02188 completely reverses flow-mediated inhibition of TNF-induced JNK activation in endothelial cells, while MEK1 inhibitor PD184352 (at ERK1/2-blocking concentrations) has no effect. This establishes MEK5-BMK1 (ERK5) as the required pathway mediating atheroprotective flow inhibition of JNK, distinct from MEK1-ERK1/2. Pharmacological inhibitor (BIX02188 vs PD184352) comparison, shear stress application, JNK activity assays in endothelial cells Biochemical and biophysical research communications Medium 18358237
2008 BIX02188 and BIX02189 are selective inhibitors of MEK5 catalytic function that block ERK5 phosphorylation without affecting ERK1/2 phosphorylation in sorbitol-stimulated HeLa cells, and inhibit MEF2C transcriptional activation downstream of MEK5/ERK5. In vitro kinase assay with purified MEK5 enzyme, cellular ERK5/ERK1/2 phosphorylation assays, MEF2C trans-reporter assay Biochemical and biophysical research communications High 18834865
2009 Constitutive activation of MEK5/ERK5 signaling in endothelial cells strongly inhibits cell migration and increases focal contact number/size with altered actin organization, due to decreased expression of p130Cas, a key regulator of directed cell migration. This identifies MEK5/ERK5 as a regulator of endothelial cell migration and focal contact turnover. Retroviral constitutively active MEK5 overexpression, migration assays, Western blotting for p130Cas, fluorescence microscopy of focal contacts and actin The Journal of biological chemistry Medium 19605361
2009 MEK5 acts as a downstream mediator of VEGF and antagonizes Epac/Rap1 anti-angiogenic signaling by inducing Id1 and suppressing TSP1 expression in endothelial cells. Overexpression studies, Western blotting, in vivo angiogenesis assays, epistasis analysis Blood Low 19710505
2009 MEK5 and ERK5 are required for the pro-myogenic actions of IGF-2 in C2 myoblasts. ERK5 translocates from cytoplasm to nucleus upon activation by upstream MEK5, while dominant-negative ERK5AEF-GFP (phospho-acceptor mutant) remains cytoplasmic. Constitutively active MEK5 rescues IGF-2 knockdown myogenic defects; dominant-negative MEK5 blocks IGF-2-induced myogenesis. GFP-tagged ERK5 live imaging for localization, constitutively active/dominant-negative MEK5 rescue/block experiments, antisense IGF-2 knockdown, kinase activity assays Journal of cell science Medium 19654213
2011 MEK5-ERK5 pathway has a non-redundant role in thymocyte apoptosis: dominant-negative MEK5 inhibits and constitutively active MEK5 promotes thymocyte apoptosis. ERK5 activity correlates with Nur77 family member levels (not Bim), and MEK5 has no function in positive selection. This is distinct from ERK1/2 function in T cell development. Retroviral expression of dominant-negative or constitutively active MEK5 in primary thymocytes, apoptosis assays, Nur77/Bim expression analysis The EMBO journal Medium 18548009
2011 MEK5 activation by laminar shear stress in human dermal microvascular endothelial cells activates ERK5, which in turn induces KLF4 expression (ERK5-dependent). MEK5/CA-transduced HDMECs show increased KLF4, thrombomodulin, eNOS, and ICAM-1 expression, and reduced TNF responsiveness partly mediated by KLF4. siRNA knockdown of ERK5 or KLF4 confirms the MEK5→ERK5→KLF4 pathway. Laminar shear stress application, retroviral MEK5/CA overexpression, siRNA knockdown of ERK5 and KLF4, Western blotting, microarrays, FACS Microcirculation 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 hyperactivation of ERK5, and loss of XIAP promotes MEK5-ERK5-MEKK2/3-dependent differentiation of human primary skeletal myoblasts. Co-immunoprecipitation, ubiquitination assays, K63-linkage-specific ubiquitin analysis, XIAP/cIAP1 siRNA/knockout, myoblast differentiation assays The EMBO journal High 24975362
2017 YAP promotes myogenic differentiation via the MEK5-ERK5 pathway through activation of the Abl/Src/MEKK3/MEK5/ERK5 kinase cascade. YAP co-immunoprecipitates with MEKK3 and ERK5. MEKK3 contains a PPGY motif (aa 178-181) that interacts with YAP; site-directed mutagenesis of MEKK3 Y181F inhibits MEK5/ERK5 activation and myogenic differentiation. Co-immunoprecipitation, site-directed mutagenesis, stable cell line overexpression, pharmacological inhibitors of c-Abl/Src/MEK5, Western blotting, myogenesis assays FASEB journal Medium 28356344
2018 MAP2K5 variants A321T and M367T (located in the kinase domain) identified in familial non-medullary thyroid carcinoma patients constitutively phosphorylate ERK5 at Ser731+Thr733 or Ser496, promote ERK5 nuclear translocation, alter downstream target gene expression, and induce thyroid epithelial cell malignant transformation. Whole exome/target sequencing, functional overexpression of MAP2K5 variants, Western blotting for ERK5 phosphorylation, nuclear translocation assays, gene expression analysis, transformation assays International journal of cancer Medium 30132833
2018 Upon acute KRAS suppression in PDAC, an ERK1/2-inhibition-induced feedforward mechanism dependent on EGFR and SRC activates ERK5 (via MEK5), which phosphorylates MYC at S62, preventing MYC proteasomal degradation. Concurrent inhibition of ERK1/2 and ERK5 synergistically causes MYC loss and suppresses PDAC growth. Kinome-wide proteomics, high-throughput screen for MYC degradation, pharmacological ERK1/2 and ERK5 inhibition, MYC phosphorylation assays Cancer cell High 30423298
2019 Resistance to ERK inhibitor SCH772984 in BRAF V600E melanoma involves stimulation of the IGF1R-MEK5-ERK5 signaling pathway, which counteracts inhibition of ERK1/2 activation. IGF1R inhibition with linsitinib blocks ERK5 activation in SCH-resistant cells and decreases their growth in 3D spheroid assays and in NSG mice. Drug resistance cell line generation, Western blotting for pathway activation, pharmacological inhibition of IGF1R, 3D spheroid assays, xenograft mouse models Cancer research Medium 30833419
2019 MEK5 knockdown by RNAi sensitizes prostate cancer cells to ionizing radiation and etoposide by impairing phosphorylation of the catalytic subunit of DNA-PK at Ser2056, delaying resolution of γH2AX and 53BP1 foci, and compromising nonhomologous end joining (NHEJ) DNA repair. MEK5 silencing combined with irradiation strongly inhibits tumor growth in mouse xenografts. RNAi knockdown, clonogenic survival assays, γH2AX/53BP1 foci analysis, DNA-PK phosphorylation Western blots, NHEJ cell-based assay, xenograft mouse model Oncogene High 31980741
2020 MEK5-ERK5 axis promotes SCLC cell survival and expansion in vitro and in vivo, and controls lipid metabolism including the mevalonate/cholesterol synthesis pathway. Loss of MEK5/ERK5 sensitizes SCLC cells to pharmacological mevalonate pathway inhibition by statins. MEK5/ERK5 knockdown/overexpression, transcriptomics, lipidomics, pharmacological statin combination, in vivo tumor growth assays Cancer research Medium 31969375
2020 The MEKK3-MEK5-ERK5 kinase cascade is required for basal mitochondrial degradation (mitophagy) through lysosome-mediated pathways, independent of exogenous mitochondrial damage, bulk autophagy, damage-induced mitophagy, or restraint of mitochondrial biogenesis. Genetic and pharmacological inhibition of MEKK3-MEK5-ERK5 pathway, mitochondrial content quantification, lysosome-mediated degradation assays Cell death discovery Medium 33101709
2020 MEK5/ERK5 signaling mediates IL-4-induced M2 macrophage differentiation through regulation of c-Myc expression. Pharmacological MEK5 inhibition reduces M2 markers (Arg-1, Ym-1, Fizz-1) and M2 chemokines/cytokines. Myeloid-specific Erk5 knockout (LysMcre/Erk5f/f mice) confirms ERK5 requirement. ERK5 regulates M2 differentiation independently of STAT3/STAT6 phosphorylation. Pharmacological MEK5/ERK5 inhibition, myeloid-specific conditional Erk5 knockout mice, Western blotting for STAT3/STAT6, qPCR for M2 markers Journal of leukocyte biology High 32745297
2012 REST transcription factor promotes primordial germ cell (PGC) survival in part by regulating Mek5 expression. Mek5 is a downstream REST-target candidate gene that is downregulated in REST-deficient PGCs. A Mek5 mutation, like the REST mutation, increases PGC apoptosis, placing Mek5 in the REST-dependent PGC survival pathway. PGC-specific conditional REST mutation, Mek5 mutation analysis, apoptosis assays in embryos, gene expression analysis Developmental biology Medium 23022299
2019 MEK5 inhibition by BIX02188/BIX02189 activates the autophagy-lysosome pathway (ALP) in an mTOR- and ERK5-independent manner, reducing p62 levels and increasing LC3-II/LC3-I ratio. MEK5 inhibition alleviates TDP-43 mislocalization and cell death in neuronal cells, identifying MEK5 as a novel autophagy modulator acting through a non-canonical pathway. MEK5 inhibitor treatment, mTOR pathway analysis, LC3-II/LC3-I ratio, p62 Western blotting, TDP-43 localization in neuronal cells Biochemical and biophysical research communications Medium 31005259
2023 MEK5-ERK5-STAT3 pathway is required for maintaining glioma stem cell (GSC) stemness and tumorigenicity. ERK5 silencing in GSCs suppresses self-renewal and GBM growth concomitant with downregulation of STAT3 phosphorylation; STAT3 introduction counteracts the GSC phenotypes caused by ERK5 silencing, placing STAT3 downstream of ERK5 in this pathway. shRNA knockdown, constitutively active MEK5/ERK5 overexpression, STAT3 rescue experiment, RNA sequencing, in vivo GBM growth assays Cancer research communications Medium 36968222
2025 Aberrant MEK5 splicing mediated by the splicing factor RBM39 is required for multiple myeloma cell survival. Full-length MEK5 maintains MM cell survival, whereas aberrant MEK5 isoforms with exon loss are non-functional and prone to proteasomal degradation. Targeting RBM39 or MEK5 synergistically increases bortezomib cytotoxicity in MM cells via inhibition of p65 (NF-κB). RBM39 knockdown/indisulam-mediated degradation, splice isoform analysis, overexpression of MEK5 isoforms, bortezomib combination cytotoxicity assays, p65 Western blotting Blood advances Medium 40048740
2025 MEK5/ERK5 co-inhibition with MEK inhibitor causes sustained G1 cell cycle arrest in NRAS-mutant melanoma by suppressing Cyclin D1 and E2F-mediated gene expression. Forced expression of Cyclin D1 and CDK4 restores cell cycle progression in MEKi/ERK5i-treated cells, identifying Cyclin D/CDK4 as the key downstream target of combined MEK/ERK5 inhibition. Transcriptome analysis, pharmacological MEKi/ERK5i combination, constitutive Cyclin D1/CDK4 overexpression rescue, cell cycle FACS analysis Cell death & disease Medium 41053077
2025 MEK5-ERK5 pathway activates Hedgehog-GLI signaling: ERK5 silencing reduces GLI1 and GLI2 protein levels and transcriptional activity in melanoma cells, while constitutively active MEK5DD increases GLI1/GLI2 levels and GLI transcriptional activity. ERK5 is required for Hedgehog-GLI-dependent melanoma cell proliferation. shRNA ERK5 knockdown, constitutively active MEK5DD overexpression, GLI luciferase reporter assay, pharmacological MEK5/ERK5 inhibitors, 3D spheroid assays Cellular oncology Medium 39998753

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 187 7499418
2011 MEK5/ERK5 pathway: the first fifteen years. Biochimica et biophysica acta 161 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 157 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 139 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 135 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 83 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
2020 The MEK5-ERK5 Kinase Axis Controls Lipid Metabolism in Small-Cell Lung Cancer. Cancer research 61 31969375
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 60 34299213
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
2015 SATB2 suppresses the progression of colorectal cancer cells via inactivation of MEK5/ERK5 signaling. The FEBS journal 56 25662172
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
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
2016 MEK5/ERK5 signaling inhibition increases colon cancer cell sensitivity to 5-fluorouracil through a p53-dependent mechanism. Oncotarget 49 27144434
2019 Resistance to MAPK Inhibitors in Melanoma Involves Activation of the IGF1R-MEK5-Erk5 Pathway. Cancer research 48 30833419
2018 A kinome-wide high-content siRNA screen identifies MEK5-ERK5 signaling as critical for breast cancer cell EMT and metastasis. Oncogene 47 29713055
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
2015 Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation. Cell death & disease 44 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 41 32277933
2019 MEK5/ERK5 activation regulates colon cancer stem-like cell properties. Cell death discovery 40 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
2020 MEK5/ERK5 signaling mediates IL-4-induced M2 macrophage differentiation through regulation of c-Myc expression. Journal of leukocyte biology 32 32745297
2009 MEK5/ERK5 signaling modulates endothelial cell migration and focal contact turnover. The Journal of biological chemistry 31 19605361
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
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
2018 The MEK5/ERK5 mitogen-activated protein kinase cascade is an effector pathway of bone-sustaining bisphosphonates that regulates osteogenic differentiation and mineralization. Bone 21 29567200
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
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
2021 Inhibition of MEK5/ERK5 signaling overcomes acquired resistance to the third generation EGFR inhibitor, osimertinib, via enhancing Bim-dependent apoptosis. Cancer letters 17 34245854
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 The Hedgehog-GLI Pathway Regulates MEK5-ERK5 Expression and Activation in Melanoma Cells. International journal of molecular sciences 15 34681917
2023 MEK5-ERK5 Axis Promotes Self-renewal and Tumorigenicity of Glioma Stem Cells. Cancer research communications 14 36968222
2023 Pathophysiological Impact of the MEK5/ERK5 Pathway in Oxidative Stress. Cells 14 37190064
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 14 34498365
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
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
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
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 13 31749391
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
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
2021 Map2k5-Deficient Mice Manifest Phenotypes and Pathological Changes of Dopamine Deficiency in the Central Nervous System. Frontiers in aging neuroscience 8 34168549
2020 MEKK3-MEK5-ERK5 signaling promotes mitochondrial degradation. Cell death discovery 8 33101709
2016 MEK5 overexpression is associated with the occurrence and development of colorectal cancer. BMC cancer 8 27160304
2018 Haplotype Association of the MAP2K5 Gene with Antipsychotics-Induced Symptoms of Restless Legs Syndrome among Patients with Schizophrenia. Psychiatry investigation 5 29422930
2024 A network-based drug prioritization and combination analysis for the MEK5/ERK5 pathway in breast cancer. BioData mining 4 38378612
2023 Potentially functional genetic variants in RPS6KA4 and MAP2K5 in the MAPK signaling pathway predict HBV-related hepatocellular carcinoma survival. Molecular carcinogenesis 4 37278562
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 4 35368675
2025 MEK5/ERK5 inhibition sensitizes NRAS-mutant melanoma to MAPK-targeted therapy by preventing Cyclin D/CDK4-mediated G1/S progression. Cell death & disease 3 41053077
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
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

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