Affinage

MAPK7

Mitogen-activated protein kinase 7 · UniProt Q13164

Length
816 aa
Mass
88.4 kDa
Annotated
2026-04-28
100 papers in source corpus 44 papers cited in narrative 44 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAPK7 (ERK5/BMK1) is an atypical MAP kinase that integrates mitogenic, mechanical, and stress signals to regulate cardiovascular development, immune cell function, cell proliferation, and differentiation through both catalytic and non-catalytic mechanisms. Activated by MEK5-mediated dual TEY phosphorylation downstream of MEKK2/3 (itself regulated by WNK1, PIEZO1-CaMKII, and XIAP/cIAP1-mediated K63 ubiquitination), ERK5 phosphorylates substrates including MEF2C, PML, and RSK, and uniquely possesses a C-terminal transcriptional activation domain that directly coactivates MEF2 transcription factors to drive expression of KLF2, NRF2, LKLF, and c-Jun (PMID:11046135, PMID:16166637, PMID:20832753, PMID:16626623, PMID:14681216). During mitosis, CDK1 phosphorylates ERK5 at C-terminal sites independently of MEK5, inhibiting its activity and regulating nucleo-cytoplasmic shuttling, while selective kinase inhibitors paradoxically activate ERK5's transcriptional domain through forced nuclear translocation, demonstrating that many biological functions attributed to ERK5—including roles in endothelial survival, embryonic vascular development, macrophage efferocytosis, M2 polarization, and stem cell pluripotency—arise substantially from its non-catalytic transcriptional activity (PMID:20736311, PMID:27679845, PMID:32915196, PMID:12093914, PMID:25001623, PMID:27498864). ERK5 S496 phosphorylation drives senescence-associated phenotypes in macrophages via NRF2 SUMOylation and AHR upregulation, and knock-in mice bearing an S496A mutation are protected from atherosclerosis (PMID:37264926).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1995 High

    Identification of ERK5/BMK1 as a structurally distinct MAP kinase with a unique C-terminal extension established that an additional mammalian MAPK cascade existed beyond ERK1/2, JNK, and p38.

    Evidence cDNA cloning and primary structure analysis revealing 816-aa protein with TEY motif and distinctive loop-12/C-terminal domain

    PMID:7646528

    Open questions at the time
    • No activating kinase or physiological stimulus identified
    • Function of C-terminal extension unknown
  2. 1998 High

    Demonstration that MEK5 activates ERK5 in response to EGF independently of Ras, and that dominant-negative ERK5 blocks EGF-induced proliferation, established ERK5 as a functionally distinct MAPK cascade required for mitogenic signaling.

    Evidence Dominant-negative ERK5 overexpression blocking EGF-induced S-phase entry; kinase activity assays in multiple cell types

    PMID:9790194

    Open questions at the time
    • Upstream kinases activating MEK5 not identified
    • Direct substrates of ERK5 unknown
  3. 2000 High

    Discovery that ERK5's C-terminal region contains an intrinsic transcriptional activation domain and directly coactivates MEF2 transcription factors revealed a dual kinase/transcription factor architecture unique among MAP kinases.

    Evidence Yeast two-hybrid screen with MEF2D MADS domain as bait; domain deletion and luciferase reporter assays confirming coactivation

    PMID:11046135

    Open questions at the time
    • Whether transcriptional activation requires kinase activity not resolved
    • Target genes of ERK5-MEF2 axis not identified
  4. 2001 High

    ERK5 was placed in retrograde neurotrophin signaling (Trk→ERK5→CREB→survival) and downstream of RET/GDNF via MEK5, broadening its receptor inputs and establishing a specific role in neuronal survival distinct from ERK1/2.

    Evidence Compartmentalized neuron cultures with dominant-negative ERK5 blocking retrograde survival; RET Y1062F mutagenesis abolishing ERK5 activation

    PMID:11237712 PMID:11544482

    Open questions at the time
    • Direct phosphorylation of CREB by ERK5 not demonstrated
    • Whether ERK5 transcriptional domain contributes to neuronal survival unknown
  5. 2002 High

    ERK5 knockout mice dying at E9.5–10.5 with severe cardiovascular defects established ERK5 as essential for vascular development and cardiac morphogenesis in vivo.

    Evidence Constitutive Erk5 gene knockout in mice with histological analysis showing endothelial disorganization and vascular remodeling failure

    PMID:12093914 PMID:14675480

    Open questions at the time
    • Cell-type-specific contributions (endothelial vs. cardiomyocyte) not resolved by constitutive knockout
    • Whether kinase activity or transcriptional domain mediates developmental function unknown
  6. 2003 High

    Identification of WNK1→MEKK2/3→MEK5 as the upstream kinase cascade and MEK5α/β splice variant regulation defined the complete four-tier kinase module activating ERK5.

    Evidence Co-IP of WNK1 with MEKK2/3, in vitro phosphorylation, siRNA knockdown of WNK1 reducing EGF-induced ERK5 activation; MEK5α vs. MEK5β differential binding to ERK5

    PMID:14583600 PMID:14681216

    Open questions at the time
    • Physiological contexts where WNK1 is the dominant ERK5 activator not defined
    • How MEK5 splice variant ratio is regulated unknown
  7. 2004 High

    Conditional ERK5 deletion in adult mice causing endothelial apoptosis, blood vessel leakage, and lethality within weeks—with MEF2C identified as a direct substrate—demonstrated that ERK5 is continuously required for adult vascular integrity through MEF2C phosphorylation.

    Evidence Mx1-Cre inducible conditional knockout; endothelial-specific deletion recapitulating phenotype; in vitro MEF2C substrate assay

    PMID:15085193

    Open questions at the time
    • Full spectrum of MEF2C target genes downstream of ERK5 in endothelium not mapped
    • Relative contribution of kinase vs. transcriptional domain to endothelial survival not resolved
  8. 2005 High

    Identification of LKLF/KLF2 as a direct transcriptional target of ERK5-MEF2 axis (requiring both kinase and C-terminal transactivation domains) established the key downstream effector genes mediating ERK5 vascular and anti-inflammatory functions.

    Evidence Gene expression profiling of erk5−/− embryos reconstituted with full-length vs. C-terminally truncated ERK5

    PMID:16166637

    Open questions at the time
    • ChIP evidence for direct MEF2 occupancy at LKLF promoter not shown
    • Whether LKLF alone accounts for vascular phenotype not tested
  9. 2006 High

    ERK5 was shown to directly phosphorylate and activate RSK through CD domain–D domain interaction, and to promote NF-κB activation via RSK2-mediated IκB degradation at G2-M, connecting ERK5 to cell cycle progression and NF-κB signaling.

    Evidence In vitro kinase assay, Co-IP, domain mutagenesis for ERK5-RSK; cell cycle synchronization linking ERK5→RSK2→NF-κB→cyclin B1 transcription

    PMID:16626623 PMID:17452529

    Open questions at the time
    • Whether RSK is a major physiological ERK5 substrate in vivo not established
    • NF-κB dependence observed in one cell system
  10. 2008 High

    ERK5 was placed in atheroprotective shear stress signaling (MEK5-ERK5 mediating flow-dependent JNK suppression) and in thymocyte apoptosis regulation via Nur77, extending ERK5 functions to mechanosensing and immune cell development.

    Evidence Selective MEK5 inhibitor BIX02188 in endothelial shear stress assay; dominant-negative/constitutively active MEK5 in thymocyte apoptosis with Nur77 expression analysis

    PMID:18358237 PMID:18548009

    Open questions at the time
    • Mechanosensor upstream of MEK5-ERK5 in shear stress not identified at this point
    • Whether ERK5 directly phosphorylates Nur77 not tested
  11. 2010 High

    Discovery that CDK1 phosphorylates ERK5 at multiple C-terminal sites during mitosis—independently of MEK5—to inhibit ERK5 and regulate its nuclear-cytoplasmic shuttling revealed a non-canonical regulation mechanism decoupling mitotic ERK5 phosphorylation from its activation.

    Evidence Mass spectrometry identification of five mitotic phosphorylation sites; CDK1 Co-IP with ERK5; CDK1 inhibitor RO3306 reversing phosphorylation; mutagenesis validating functional consequences

    PMID:20667468 PMID:20736311

    Open questions at the time
    • Functional consequence of CDK1-mediated ERK5 inhibition during mitosis not fully defined
    • Whether CDK1 phosphorylation affects C-terminal transcriptional domain directly not tested
  12. 2010 High

    Identification of PML as a direct ERK5 substrate whose tumor-suppressor function (p21 induction) is inhibited by ERK5 phosphorylation provided a direct oncogenic mechanism, validated by the ERK5 inhibitor XMD8-92 suppressing tumor growth in vivo.

    Evidence Co-IP of ERK5 with PML, in vitro phosphorylation, p21 reporter suppression, xenograft tumor model with 95% growth suppression by XMD8-92

    PMID:20832753

    Open questions at the time
    • PML phosphorylation sites by ERK5 not mapped
    • XMD8-92 selectivity later questioned (bromodomain off-targets)
  13. 2014 High

    XIAP and cIAP1 were identified as negative regulators of ERK5 signaling through K63-linked ubiquitination of MEKK2/3, which disrupts the MEKK2/3-MEK5 interaction, revealing a ubiquitin-dependent mechanism that restrains ERK5 pathway activation.

    Evidence Co-IP, K63-linked ubiquitin chain analysis, PB1 domain competition assays, skeletal myoblast differentiation readout

    PMID:24975362

    Open questions at the time
    • Physiological triggers that relieve XIAP/cIAP1-mediated suppression not identified
    • Whether K63 ubiquitination also affects MEKK2/3 stability not tested
  14. 2014 High

    Macrophage-specific ERK5 deletion revealed ERK5 is required for efferocytosis and protection from atherosclerosis, while ERK5 also mediates IFN-γ-induced LRRK2 expression, establishing ERK5 as a central node in macrophage immune function.

    Evidence Macrophage-specific conditional ERK5 knockout crossed to LDLR−/− mice; efferocytosis assays; ERK5 siRNA and inhibitor reducing LRRK2 induction

    PMID:24479685 PMID:25001623

    Open questions at the time
    • Direct ERK5 substrates mediating efferocytosis not identified
    • Whether kinase activity or transcriptional domain required for macrophage functions not distinguished
  15. 2016 High

    The landmark finding that selective ERK5 kinase inhibitors lack antiproliferative or anti-inflammatory activity—and that prior inhibitor efficacy derived from off-target bromodomain inhibition—established that ERK5's major biological functions depend on its non-catalytic transcriptional domain rather than kinase activity alone.

    Evidence Synthesis of highly selective ERK5 inhibitors; KINOMEscan and BROMOscan profiling demonstrating bromodomain cross-reactivity of XMD8-92 and BIX02189; functional assays showing no effect of selective kinase inhibition

    PMID:27679845

    Open questions at the time
    • Whether any ERK5 kinase substrates are physiologically relevant remains uncertain
    • Mechanism by which kinase domain occupancy affects C-terminal domain not resolved
  16. 2016 High

    ERK5 maintains naive pluripotency in embryonic stem cells and suppresses neuroectoderm/cardiomyocyte differentiation, with CRISPR knockout distinguishing ERK5-specific from BRD4-dependent functions; concurrently, ERK5 was shown to serve as a bypass proliferative route when ERK1/2 is deleted in intestinal epithelium.

    Evidence CRISPR/Cas9 ERK5 knockout in ESCs with selective compound comparison; conditional ERK1/2 knockout in intestinal epithelium with MEK5 inhibitor combination in organoids and CRC lines

    PMID:27187615 PMID:27498864

    Open questions at the time
    • Transcriptional targets of ERK5 in pluripotency maintenance not defined
    • Whether ERK5 bypass in ERK1/2-null cells requires kinase activity not tested
  17. 2020 High

    The paradox that ERK5 kinase inhibitors activate ERK5's transcriptional domain by promoting nuclear translocation explained why kinase inhibition fails to recapitulate genetic deletion phenotypes, fundamentally reframing therapeutic targeting strategies for ERK5.

    Evidence Panel of selective ERK5 inhibitors tested with dual kinase activity and transcriptional reporter assays; nuclear localization imaging

    PMID:32915196

    Open questions at the time
    • Structural mechanism linking kinase domain occupancy to conformational change enabling nuclear import not resolved
    • Whether degrader approaches can overcome paradoxical activation not tested
  18. 2020 High

    ERK5 was shown to be required for IL-4-induced M2 macrophage polarization through c-Myc (independently of STAT3/STAT6), expanding its immune functions beyond efferocytosis to alternative macrophage activation.

    Evidence Myeloid-specific conditional ERK5 knockout (LysMcre/Erk5f/f) plus MEK5/ERK5 pharmacological inhibition; M2 marker and c-Myc expression analysis

    PMID:32745297

    Open questions at the time
    • Whether ERK5 directly regulates c-Myc transcription or stability not resolved
    • In vivo consequence of ERK5-dependent M2 polarization defect not tested
  19. 2022 Medium

    PIEZO1 was identified as the mechanosensor upstream of ERK5 in endothelial shear stress signaling, activating CaMKII which directly interacts with MEKK3 to drive MEKK3/MEK5/ERK5-dependent KLF2/4 transcription, completing the mechanotransduction pathway from membrane to nucleus.

    Evidence Endothelial-specific Piezo1 knockout mice; CaMKII-MEKK3 Co-IP; calcium imaging; shear stress experiments measuring KLF2/4

    PMID:35883633

    Open questions at the time
    • CaMKII phosphorylation site on MEKK3 not mapped
    • Whether PIEZO1-ERK5 axis operates in non-endothelial mechanosensing contexts unknown
  20. 2023 High

    ERK5 S496 phosphorylation was identified as a switch controlling senescence-associated secretory phenotype and stemness in macrophages by inducing NRF2 SUMOylation at K518, with S496A knock-in mice protected from atherosclerosis, providing the first phosphosite-specific in vivo ERK5 disease mechanism.

    Evidence CRISPR/Cas9 S496A knock-in mice; imaging mass cytometry; NRF2 SUMOylation assays; atherosclerosis model

    PMID:37264926

    Open questions at the time
    • Kinase responsible for S496 phosphorylation not identified
    • Whether S496 phosphorylation affects ERK5 transcriptional domain function not tested
    • Generalizability of S496-NRF2 SUMOylation axis beyond macrophages unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • The central unresolved question is how to therapeutically target ERK5 given that kinase inhibition paradoxically activates its transcriptional domain; additionally, the structural basis for how kinase domain occupancy triggers conformational opening and nuclear translocation, the relative contributions of kinase versus transcriptional functions across different tissues, and the identity of the kinase that phosphorylates ERK5 at S496 remain unknown.
  • Structural mechanism coupling kinase domain occupancy to C-terminal conformational change and nuclear import not determined
  • No ERK5-selective degrader or dual kinase/transcription-domain inhibitor reported
  • Kinase phosphorylating S496 unknown
  • Comprehensive in vivo substrate repertoire for ERK5 kinase activity not established

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 3 GO:0140110 transcription regulator activity 3
Localization
GO:0005634 nucleus 4 GO:0005829 cytosol 2
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-1266738 Developmental Biology 3 R-HSA-1640170 Cell Cycle 3 R-HSA-168256 Immune System 3 R-HSA-74160 Gene expression (Transcription) 3 R-HSA-5357801 Programmed Cell Death 2
Partners
CDK1MEF2CMEF2DMEK5MEKK2MEKK3PMLRPS6KA1

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 BMK1/MAPK7 (ERK5) was identified as a new human MAP kinase of 816 amino acids with the dual phosphorylation TEY motif characteristic of MAP kinases, but with a distinct C-terminal domain and loop-12 structure compared to other mammalian MAP kinases, suggesting it regulates signaling events distinct from the ERK group. cDNA cloning, primary structure analysis Biochemical and biophysical research communications High 7646528
1998 EGF activates BMK1/ERK5 independently of Ras through the MAP kinase kinase MEK5, and expression of a dominant-negative BMK1 blocks EGF-induced cell proliferation and S-phase entry, establishing BMK1 as part of a distinct MAP kinase signaling pathway required for EGF-induced cell proliferation. Dominant-negative overexpression, kinase activity assays, cell cycle analysis Nature High 9790194
2000 ERK5 was isolated in a yeast two-hybrid screen using the MADS-MEF2 domain of MEF2D as bait; the C-terminal region of ERK5 contains both a MEF2-interacting domain and a potent transcriptional activation domain required for coactivation of MEF2D, revealing ERK5 as a MAP kinase with intrinsic transcriptional activation capability. Yeast two-hybrid, domain deletion analysis, luciferase reporter assays, endogenous gene activation Molecular and cellular biology High 11046135
2001 During retrograde neurotrophin signaling, endocytosed Trk receptors activate the ERK5 pathway, leading to nuclear translocation of ERK5, phosphorylation of CREB, and enhanced neuronal survival; ERK1/2 does not transmit this retrograde signal, establishing a unique function for ERK5 in retrograde signaling. Dominant-negative ERK5 expression, compartmentalized neuron culture, nuclear translocation imaging, CREB phosphorylation assay, survival assay Nature neuroscience High 11544482
2001 EGF-induced activation of MKK5 and ERK5 occurs subsequent to activation of ERK1 and ERK2 in HeLa cells, and the ERK1/2 cascade negatively controls the MKK5/ERK5 pathway; ERK5 is not a significant activator of MAPK-activated protein kinase-1/RSK in HeLa cells. Phospho-specific antibodies, MEK inhibitor dose-response (U0126, PD184352), kinase activity assays FEBS letters Medium 11478941
2002 Erk5 knockout mice die around E9.5–10.5 with defective blood vessel and cardiac development; endothelial cells lining the developing myocardium display disorganized, rounded morphology, and blood vessel investment with smooth muscle cells is attenuated, establishing an essential role for Erk5 in cardiovascular development and angiogenesis. Gene knockout in mice, histological and morphological analysis Proceedings of the National Academy of Sciences of the United States of America High 12093914
2003 ERK5 knockout mice die at approximately E10.5 with increased apoptosis in cephalic mesenchyme, vascular remodeling defects, cardiac development abnormalities, and placental defects, confirming that ERK5 is essential for early embryonic development and normal vascular system development. Gene targeting/knockout in mice, in situ hybridization, apoptosis analysis BMC developmental biology High 14675480
2003 WNK1 activates ERK5 through an MEKK2/3-dependent mechanism: WNK1 co-immunoprecipitates with MEKK2 and MEKK3, phosphorylates both in vitro, and WNK1-driven ERK5 activation is blocked by dominant-negative MEKK2/3 or MEK5; siRNA knockdown of WNK1 attenuates EGF-induced ERK5 activation, placing WNK1 upstream of MEKK2/3 in the ERK5 pathway. Co-immunoprecipitation, dominant-negative overexpression, in vitro kinase assay, siRNA knockdown The Journal of biological chemistry High 14681216
2003 Activation of the MEK5-ERK5 pathway causes phosphorylation and stabilization of c-Fos and Fra-1, with the C-terminal half of ERK5 required for maximal transactivation activity of c-Fos and Fra-1; ERK5-mediated phosphorylation of c-Fos occurs at sites distinct from those targeted by ERK1/2. Constitutively active MEK5 expression, phosphorylation mapping, reporter assays Genes to cells : devoted to molecular & cellular mechanisms Medium 12622723
2003 The full-length MEK5α splice variant, but not MEK5β, activates BMK1/ERK5 and induces nuclear translocation; MEK5β acts as a dominant negative by binding BMK1 and preventing MEK5α association with BMK1, revealing splice variant-dependent control of ERK5 activation. Co-immunoprecipitation, dominant-negative and constitutively active constructs, MEF2 reporter assays, kinase activation assays The Journal of biological chemistry High 14583600
2004 Conditional ablation of BMK1 in adult mice leads to lethality within 2–4 weeks, blood vessel leakage, endothelial cell rounding and apoptosis; in vitro BMK1 removal causes endothelial cell death partly through deregulation of MEF2C, a direct substrate of BMK1; endothelial-specific but not cardiomyocyte-specific deletion recapitulates cardiovascular defects. Mx1-Cre inducible conditional knockout, histology, endothelial cell culture, MEF2C substrate assay The Journal of clinical investigation High 15085193
2001 BMK1/ERK5 is activated via tyrosine 1062 of the RET tyrosine kinase upon GDNF stimulation or MEN2A mutation; this activation requires downstream MEK5 signaling (blocked by dominant-negative MEK5), but not RAS or PI3K pathways; activated BMK1 in turn activates the MEF2C transcription factor. Tyrosine-to-phenylalanine mutagenesis (Y1062F), kinase activity assays, MEK1/PI3K inhibitors, dominant-negative MEK5, MEF2C luciferase reporter Biochemical and biophysical research communications Medium 11237712
2005 ERK5 drives LKLF (lung Krüppel-like factor) transcription by activating MEF2 transcription factors through its kinase and transcriptional activation domains; gene profile analysis of erk5-/- embryos and fibroblasts reconstituted with ERK5 or truncated ERK5(1-740, lacking transactivation domain) identified LKLF, flt1, and bnip3 as ERK5 target genes. Gene expression profiling (microarray) in knockout vs. reconstituted cells, shRNA/dominant-negative MEK5, ChIP-like transcription factor assays Molecular and cellular biology High 16166637
2005 The MEK5-ERK5 pathway is required for neural differentiation in Xenopus embryos: morpholino knockdown of ERK5 or MEK5 reduces head structure and inhibits neural differentiation, while forced activation of MEK5-ERK5 is sufficient to induce neural differentiation; the pathway acts downstream of SoxD and upstream of the proneural gene Xngnr1. Morpholino antisense knockdown, constitutively active MEK5 expression, epistasis analysis in Xenopus embryos EMBO reports High 16179948
2006 ERK5 binds to and phosphorylates p90 RSK: ERK5 co-immunoprecipitates with RSK from cell extracts, binds RSK in vitro, and phosphorylates RSK to activate it; the common docking (CD) domain of ERK5 and the D domain of RSK are important for their association; activation of ERK5 weakens its binding to RSK. Co-immunoprecipitation, in vitro binding assay, in vitro kinase assay, domain mutagenesis Archives of biochemistry and biophysics High 16626623
2007 ERK5 activation by PDGF-BB in hepatic stellate cells is Src-dependent; ERK5 silencing inhibits PDGF-BB-induced cell proliferation and c-Jun expression/activation, while ERK5 depletion increases cell migration associated with redistribution of focal contacts and decreased phosphorylation of FAK, paxillin, and PAK. siRNA knockdown, Src inhibitor, migration/proliferation assays, phosphorylation analysis Journal of hepatology Medium 17998143
2007 ERK5 is activated at G2-M and required for timely mitotic entry; ERK5 activates NF-κB through RSK2-mediated phosphorylation and degradation of IκB; NF-κB inhibition at G2-M delays mitotic entry and reduces cyclin B1, cyclin B2, Plk-1, and cdc25B transcription; constitutive ERK5 activation-induced mitosis is blocked by NF-κB inhibition. Cell cycle synchronization, kinase assays, reporter assays, dominant-negative and constitutively active constructs, gene expression analysis The Journal of cell biology High 17452529
2008 MEK5-ERK5 pathway mediates fluid shear stress inhibition of TNF-α-induced JNK activation in endothelial cells; selective MEK5 inhibitor BIX02188 completely reversed flow inhibition of TNF-mediated JNK activation, while ERK1/2-selective inhibitor PD184352 had no effect, placing MEK5-ERK5 as the key mediator of atheroprotective flow signaling. Pharmacological inhibitors (BIX02188, PD184352), shear stress apparatus, JNK activity assay, NF-κB reporter Biochemical and biophysical research communications Medium 18358237
2008 EGF-induced ERK5 activation controls Slug expression in keratinocytes; ectopic Erk5 activation increases Slug mRNA and accelerates wound healing; Erk5 shRNA knockdown reduces keratinocyte motility, Slug induction, and disrupts desmosome organization, establishing an EGFR/Erk5/Slug pathway controlling cytoskeleton organization and cell motility. Erk5 shRNA knockdown, constitutively active Erk5 expression, wound healing assay, migration assay, desmosome analysis Molecular biology of the cell Medium 18716062
2008 MEK5-ERK5 pathway regulates apoptosis of developing thymocytes but has no function in positive selection; ERK5 activity correlates with levels of Nur77 family members but not Bim, distinguishing the ERK5 apoptosis pathway from ERK1/2 in T-cell development. Retroviral expression of dominant-negative and constitutively active MEK5, thymocyte apoptosis assays, Nur77/Bim expression analysis The EMBO journal High 18548009
2009 Constitutive activation of MEK5/ERK5 signaling inhibits endothelial cell migration and increases focal contact area; this is associated with reduced expression of p130Cas, a key player in directed cell migration, and altered actin organization, demonstrating ERK5 controls endothelial cell migration and morphology. Retroviral gene transfer (constitutively active MEK5), migration assays, focal contact measurement, actin imaging, p130Cas expression analysis The Journal of biological chemistry Medium 19605361
2010 ERK5 is phosphorylated during mitosis at multiple sites in its C-terminal region by CDK1 (not MEK5); CDK1 co-precipitates with ERK5 in mitotic cells; CDK1 inhibitor RO3306 reverses mitotic ERK5 phosphorylation; this CDK1-dependent phosphorylation inhibits ERK5 activity and regulates its nucleo-cytoplasmic shuttling. Co-immunoprecipitation, CDK1 inhibitor, phosphorylation site mutagenesis, nuclear/cytoplasmic fractionation Journal of cell science High 20736311
2010 ERK5 phosphorylation during mitosis occurs at its C-terminal half (not at the TEY activation motif) and is CDK-dependent rather than MEK5-dependent; five mitotic phosphorylation sites were identified; mutagenesis showed these phosphorylations inhibit ERK5 activity and regulate ERK5 nuclear-cytoplasmic shuttling. Mass spectrometry phosphorylation site identification, mutagenesis, CDK inhibitors, fractionation assays Cellular signalling High 20667468
2010 BMK1/ERK5 interacts with promyelocytic leukemia protein (PML) and inhibits its tumor-suppressor function through phosphorylation; activated BMK1 inhibits PML-dependent p21 activation; a small-molecule inhibitor XMD8-92 was developed that blocks BMK1 kinase activity and suppresses tumor growth in vivo by 95%. Co-immunoprecipitation, in vitro phosphorylation assay, p21 reporter assay, xenograft tumor model, pharmacological inhibition Cancer cell High 20832753
2013 X-ray crystal structure of the human ERK5 kinase domain in complex with a selective benzo[e]pyrimido[5,4-b]diazepine-6(11H)-one inhibitor was determined; the structure reveals specific residue differences in the ATP-binding site compared to related ERKs, p38s, and JNKs that allow development of ERK5-specific inhibitors. X-ray crystallography Journal of medicinal chemistry High 23656407
2013 ERK5 is degraded through the ubiquitin-proteasome system in a process mediated by the tumor suppressor VHL through a prolyl hydroxylation-dependent mechanism; VHL-negative cell lines have elevated ERK5, and ERK5 knockdown in these cells decreases proliferation and migration. Transfection assays, endogenous ERK5 analysis in VHL-positive and -negative cell lines, proteasome inhibitor experiments, siRNA knockdown Neoplasia (New York, N.Y.) Medium 23730213
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, directly impeding MEK5-ERK5 interaction in a trimeric complex and leading to ERK5 inactivation; loss of XIAP or cIAP1 leads to hyperactivation of ERK5. Co-immunoprecipitation, ubiquitination assays, domain competition assays, ubiquitin chain linkage analysis, skeletal myoblast differentiation assay The EMBO journal High 24975362
2014 ERK5 activation in macrophages promotes efferocytosis; macrophage-specific ERK5-null mice exhibit reduced efferocytosis and accelerated atherosclerotic plaque formation when crossed with LDL receptor-/- mice on a high-cholesterol diet; statins robustly activate ERK5 in macrophages. Macrophage-specific conditional ERK5 knockout, efferocytosis assays, atherosclerosis model (LDLR-/- mice), pharmacological ERK5 activation Circulation High 25001623
2014 IFN-γ-mediated induction of LRRK2 in macrophages is suppressed by pharmacological inhibition and RNA interference of ERK5, establishing ERK5 as a required mediator of the IFN-γ signaling pathway inducing LRRK2 expression. ERK5 pharmacological inhibition, siRNA knockdown, LRRK2 immunostaining, differentiation of THP-1 cells and primary monocytes Journal of neurochemistry Medium 24479685
2016 Genetic deletion of ERK1/2 in intestinal epithelial cells results in supraphysiological ERK5 pathway activity; combined pharmacological targeting of MEK1/2 and MEK5 is more effective than single treatment in suppressing proliferation in intestinal organoids and colorectal cancer lines, demonstrating ERK5 provides a bypass proliferative route when ERK1/2 is abrogated. Conditional ERK1/2 knockout mice, MEK1/2 and MEK5/ERK5 pharmacological inhibitors, intestinal organoid culture, CRC cell lines Nature communications High 27187615
2016 Selective ERK5 kinase inhibitors have no antiinflammatory or antiproliferative activity, whereas less selective inhibitors block both ERK5 and BET bromodomains; the source of efficacy of previously reported ERK5 inhibitors is off-target activity on bromodomains; phenotypes from genetic deletion of ERK5 likely arise from removal of a noncatalytic function. Synthesis of selective ERK5 inhibitors, bromodomain selectivity profiling (KINOMEscan, BROMOscan), cell proliferation and inflammation assays Proceedings of the National Academy of Sciences of the United States of America High 27679845
2016 ERK5 maintains embryonic stem cells in the naive pluripotent state and suppresses progression toward primed pluripotency and neuroectoderm differentiation; ERK5 also inhibits a cardiomyocyte-specific differentiation program; these functions were dissected from BRD4 functions using CRISPR/Cas9 ERK5 knockout and compound selectivity engineering. CRISPR/Cas9 knockout, selective ERK5 inhibitor/BET inhibitor comparison, pluripotency state assays, differentiation assays Cell reports High 27498864
2017 YAP promotes myogenic differentiation through the MEK5-ERK5 pathway; YAP activates the Abl/Src/MEKK3/MEK5/ERK5 kinase cascade; co-immunoprecipitation showed YAP interacts with MEKK3 and ERK5; MEKK3 PPGY motif (aa 178-181) mediates interaction with YAP, and Y181F mutation inhibits MEK5/ERK5 activation and myogenesis. Co-immunoprecipitation, site-directed mutagenesis, constitutive expression, kinase activation assays, myogenic differentiation assays FASEB journal : official publication of the Federation of American Societies for Experimental Biology Medium 28356344
2018 Mitochondrial complex I activity induces ERK5 expression through fumarate accumulation; ERK5 in turn induces MEF2-dependent NRF2 expression, activating the antioxidant response; blocking OXPHOS decreases Erk5 and Nrf2 expression in vivo, establishing an OXPHOS-fumarate-ERK5-MEF2-NRF2 axis for antioxidant response. OXPHOS inhibition, fumarate supplementation, MEF2/NRF2 reporter assays, fibroblasts from mitochondrial disorder patients, mouse model Scientific reports Medium 29743487
2018 IFN-γ receptor stimulation activates ULK1, which interacts with and phosphorylates MLK3, leading to downstream ERK5 activation; this ULK1-MLK3-ERK5 axis is required for transcription of antiviral IFN-stimulated genes (ISGs) and IFN-γ-dependent antiviral effects, independent of autophagy. Kinase interaction assays, phosphorylation analysis, antiviral assays, gene expression analysis, pathway inhibition Science signaling Medium 30459284
2019 Resistance to ERK1/2 inhibitor SCH772984 in BRAFV600E melanoma cells involves stimulation of the IGF1R-MEK5-ERK5 signaling pathway, which counteracts Erk1/2 inhibition; IGF1R inhibitor linsitinib blocked Erk5 activation in resistant cells, establishing this axis as a resistance bypass route. ERKi-resistant cell line generation, pathway analysis, IGF1R inhibitor treatment, 3D spheroid assays, xenograft models Cancer research Medium 30833419
2020 Small molecule ERK5 kinase inhibitors paradoxically activate ERK5 transcriptional transactivation domain activity by stimulating nuclear localization of ERK5; this kinase domain occupancy-driven nuclear translocation activates the C-terminal transactivation domain independently of kinase activity. ERK5 kinase and transcriptional reporter assays, nuclear localization imaging, selective ERK5 inhibitor panel Biochemical Society transactions High 32915196
2022 Mechanosensitive channel PIEZO1 senses shear force and activates CaMKII, which interacts with and activates MEKK3, promoting MEKK3/MEK5/ERK5 signaling and ultimately inducing KLF2/4 transcription in endothelial cells; endothelial-specific Piezo1 deletion reduces KLF2/4 expression in vivo. Endothelial-specific Piezo1 knockout mice, co-immunoprecipitation (CaMKII-MEKK3), calcium imaging, shear stress experiments, KLF2/4 expression analysis Cells Medium 35883633
2023 ERK5 S496 phosphorylation mediates both senescence-associated secretory phenotype (SASP) and senescence-associated stemness by upregulating AHR in macrophages; S496 phosphorylation induces NRF2 SUMOylation at K518 to inhibit NRF2 transcriptional activity without altering ERK5 catalytic activity; ERK5 S496A knock-in mice are protected from atherosclerosis. CRISPR/Cas9 knock-in (ERK5 S496A), imaging mass cytometry, bone marrow-derived macrophage isolation, RNA-seq, NRF2 SUMOylation assays, atherosclerosis model Circulation research High 37264926
2012 BMK1 signaling suppresses epithelial-mesenchymal transition (EMT): BMK1 elevation augments E-cadherin-mediated cell-cell adhesion and reduces mesenchymal markers; BMK1 depletion promotes Snail nuclear accumulation through Akt/GSK3β signaling activated by increased DEPTOR expression (mTOR inhibitor); BMK1 depletion promotes metastasis in vivo. BMK1 overexpression and siRNA knockdown, EMT marker analysis, nuclear/cytoplasmic fractionation, DEPTOR modulation, in vivo metastasis model Cancer research Medium 22282661
2017 Dichloroacetate (DCA) increases ERK5 expression through fumarate accumulation (OXPHOS induction), which activates the transcription factor MEF2 to drive LDLR transcription and LDL intake; pharmacological or genetic inhibition of the ERK5/MEF2 pathway decreases LDLR expression and LDL uptake. DCA treatment, genetic/pharmacological ERK5/MEF2 inhibition, LDLR luciferase reporter, H3K27 acetylation ChIP, primary hepatocytes, mouse models Scientific reports Medium 28878225
2020 ERK5 inhibition or silencing in endometrial cancer impairs NF-κB pathway by downregulating NEMO/IKKγ expression, leading to impaired p65/RELA activity and apoptosis; overexpression of NEMO/IKKγ rescues this apoptosis, placing ERK5 upstream of NEMO in an ERK5-NEMO-NF-κB survival pathway. ERK5 siRNA/pharmacological inhibition, MEK5 genetic deletion, NEMO rescue overexpression, xenograft model, NF-κB reporter, correlation in human EC tumor samples Cellular and molecular life sciences : CMLS Medium 36123565
2021 ERK5 inhibition induces p21-mediated cellular senescence in melanoma: genetic and pharmacological ERK5 blockade increases senescence-associated β-galactosidase activity, p21 expression, and SASP cytokines (CXCL1, CXCL8, CCL20); knockdown of p21 suppresses ERK5 inhibition-induced senescence, identifying p21 as the key mediator; confirmed in vivo in melanoma xenografts. ERK5 shRNA knockdown, XMD8-92 pharmacological inhibition, transcriptomic analysis, senescence assays (β-galactosidase), p21 siRNA rescue, xenograft model Cancer research High 34799355
2020 MEK5/ERK5 inhibition in macrophages reduces IL-4-induced M2 differentiation (Arg-1, Ym-1, Fizz-1 expression) independently of STAT3/STAT6 phosphorylation, but through decreased c-Myc expression; myeloid-specific Erk5 conditional knockout (LysMcre/Erk5f/f) confirms ERK5 requirement for IL-4-induced M2 polarization. MEK5/ERK5 pharmacological inhibition, myeloid-specific conditional ERK5 knockout, M2 marker analysis, STAT3/STAT6 phosphorylation, c-Myc expression analysis Journal of leukocyte biology High 32745297

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
1998 Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor. Nature 364 9790194
2001 Neurotrophins use the Erk5 pathway to mediate a retrograde survival response. Nature neuroscience 360 11544482
2006 MAPK signalling: ERK5 versus ERK1/2. EMBO reports 333 16880823
1995 Primary structure of BMK1: a new mammalian map kinase. Biochemical and biophysical research communications 298 7646528
2006 Regulation of cellular functions by the ERK5 signalling pathway. Cellular signalling 229 16376520
2001 Effects of MAP kinase cascade inhibitors on the MKK5/ERK5 pathway. FEBS letters 229 11478941
2000 ERK5 is a novel type of mitogen-activated protein kinase containing a transcriptional activation domain. Molecular and cellular biology 228 11046135
2004 Targeted deletion of BMK1/ERK5 in adult mice perturbs vascular integrity and leads to endothelial failure. The Journal of clinical investigation 227 15085193
2002 Erk5 null mice display multiple extraembryonic vascular and embryonic cardiovascular defects. Proceedings of the National Academy of Sciences of the United States of America 199 12093914
2012 ERK5: structure, regulation and function. Cellular signalling 182 22800864
2010 Pharmacological inhibition of BMK1 suppresses tumor growth through promyelocytic leukemia protein. Cancer cell 173 20832753
2011 MEK5/ERK5 pathway: the first fifteen years. Biochimica et biophysica acta 160 22020294
2004 Role of the BMK1/ERK5 signaling pathway: lessons from knockout mice. Journal of molecular medicine (Berlin, Germany) 138 15517128
2008 Erk5 controls Slug expression and keratinocyte activation during wound healing. Molecular biology of the cell 134 18716062
2003 WNK1 activates ERK5 by an MEKK2/3-dependent mechanism. The Journal of biological chemistry 123 14681216
2003 Knockout of ERK5 causes multiple defects in placental and embryonic development. BMC developmental biology 110 14675480
1999 Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control. The Journal of biological chemistry 109 10531364
2007 Regulation of the G2-M cell cycle progression by the ERK5-NFkappaB signaling pathway. The Journal of cell biology 90 17452529
2003 Regulation of c-Fos and Fra-1 by the MEK5-ERK5 pathway. Genes to cells : devoted to molecular & cellular mechanisms 90 12622723
2002 Cell-cycle arrest by PD184352 requires inhibition of extracellular signal-regulated kinases (ERK) 1/2 but not ERK5/BMK1. The Biochemical journal 88 12069688
2019 Impact of ERK5 on the Hallmarks of Cancer. International journal of molecular sciences 87 30901834
2017 Oncogenic signaling of MEK5-ERK5. Cancer letters 86 28153789
2005 Transcriptional regulation of tissue-specific genes by the ERK5 mitogen-activated protein kinase. Molecular and cellular biology 81 16166637
2005 Multifunctional role of Erk5 in multiple myeloma. Blood 80 15692064
2016 ERK5 signalling rescues intestinal epithelial turnover and tumour cell proliferation upon ERK1/2 abrogation. Nature communications 77 27187615
2016 ERK5 kinase activity is dispensable for cellular immune response and proliferation. Proceedings of the National Academy of Sciences of the United States of America 77 27679845
2009 ERK5 and the regulation of endothelial cell function. Biochemical Society transactions 70 19909257
2014 ERK5 activation in macrophages promotes efferocytosis and inhibits atherosclerosis. Circulation 67 25001623
2018 Phthalates promote prostate cancer cell proliferation through activation of ERK5 and p38. Environmental toxicology and pharmacology 65 30125794
2016 The MEK5/ERK5 signalling pathway in cancer: a promising novel therapeutic target. Drug discovery today 63 27320690
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
2018 ERK5 is activated by oncogenic BRAF and promotes melanoma growth. Oncogene 58 29483645
2014 Interferon-γ induces leucine-rich repeat kinase LRRK2 via extracellular signal-regulated kinase ERK5 in macrophages. Journal of neurochemistry 56 24479685
2007 ERK5 differentially regulates PDGF-induced proliferation and migration of hepatic stellate cells. Journal of hepatology 54 17998143
2000 Role of BMK1 in regulation of growth factor-induced cellular responses. Immunologic research 54 10852122
2004 BMK1 is activated in glomeruli of diabetic rats and in mesangial cells by high glucose conditions. Kidney international 53 15086914
2006 The MAP kinase ERK5 binds to and phosphorylates p90 RSK. Archives of biochemistry and biophysics 49 16626623
2014 Therapeutic potential of ERK5 targeting in triple negative breast cancer. Oncotarget 47 25350956
2002 Vascular smooth muscle cell proliferation requires both p38 and BMK1 MAP kinases. Archives of biochemistry and biophysics 47 12054430
2019 Resistance to MAPK Inhibitors in Melanoma Involves Activation of the IGF1R-MEK5-Erk5 Pathway. Cancer research 46 30833419
2009 ERK1/2, but not ERK5, is necessary and sufficient for phosphorylation and activation of c-Fos. Cellular signalling 46 19249353
2012 BMK1 kinase suppresses epithelial-mesenchymal transition through the Akt/GSK3β signaling pathway. Cancer research 45 22282661
2015 Aberrant MEK5/ERK5 signalling contributes to human colon cancer progression via NF-κB activation. Cell death & disease 43 25855966
2010 Multisite phosphorylation of Erk5 in mitosis. Journal of cell science 43 20736311
2022 Mechanosensitive Channel PIEZO1 Senses Shear Force to Induce KLF2/4 Expression via CaMKII/MEKK3/ERK5 Axis in Endothelial Cells. Cells 42 35883633
2001 Activation of BMK1 via tyrosine 1062 in RET by GDNF and MEN2A mutation. Biochemical and biophysical research communications 41 11237712
2022 Tyrosine phosphatase SHP2 exacerbates psoriasis-like skin inflammation in mice via ERK5-dependent NETosis. MedComm 40 35281792
2020 Targeted Avenues for Cancer Treatment: The MEK5-ERK5 Signaling Pathway. Trends in molecular medicine 40 32277933
2015 MAPK7 Regulates EMT Features and Modulates the Generation of CTCs. Molecular cancer research : MCR 40 25678598
2010 Alternative ERK5 regulation by phosphorylation during the cell cycle. Cellular signalling 40 20667468
2019 MEK5/ERK5 activation regulates colon cancer stem-like cell properties. Cell death discovery 39 30774996
2016 RETRACTED: The transcription factor FOXF1 promotes prostate cancer by stimulating the mitogen-activated protein kinase ERK5. Science signaling 38 27165781
2022 OXTRHigh stroma fibroblasts control the invasion pattern of oral squamous cell carcinoma via ERK5 signaling. Nature communications 36 36045118
2020 Targeting the MAPK7/MMP9 axis for metastasis in primary bone cancer. Oncogene 36 32655131
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
2018 Mitochondrial Complex I activity signals antioxidant response through ERK5. Scientific reports 35 29743487
2018 MicroRNA-143a-3p modulates preadipocyte proliferation and differentiation by targeting MAPK7. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 35 30243086
2016 Erk5 Is a Key Regulator of Naive-Primed Transition and Embryonic Stem Cell Identity. Cell reports 35 27498864
2017 MiR-143 regulates the proliferation and migration of osteosarcoma cells through targeting MAPK7. Archives of biochemistry and biophysics 34 28734729
2013 ERK5/BMK1 is a novel target of the tumor suppressor VHL: implication in clear cell renal carcinoma. Neoplasia (New York, N.Y.) 34 23730213
2017 The PDK1 Inhibitor Dichloroacetate Controls Cholesterol Homeostasis Through the ERK5/MEF2 Pathway. Scientific reports 33 28878225
2003 Differential role of MEK5alpha and MEK5beta in BMK1/ERK5 activation. The Journal of biological chemistry 33 14583600
2021 Inhibition of ERK5 Elicits Cellular Senescence in Melanoma via the Cyclin-Dependent Kinase Inhibitor p21. Cancer research 32 34799355
2020 Beyond Kinase Activity: ERK5 Nucleo-Cytoplasmic Shuttling as a Novel Target for Anticancer Therapy. International journal of molecular sciences 32 32023850
2019 The MKKK62-MKK3-MAPK7/14 module negatively regulates seed dormancy in rice. Rice (New York, N.Y.) 32 30671680
2017 MicroRNA-143 inhibits cell growth by targeting ERK5 and MAP3K7 in breast cancer. Brazilian journal of medical and biological research = Revista brasileira de pesquisas medicas e biologicas 32 28746466
2016 MicroRNA-24 promotes 3T3-L1 adipocyte differentiation by directly targeting the MAPK7 signaling. Biochemical and biophysical research communications 32 27103442
2019 MicroRNA-374b induces endothelial-to-mesenchymal transition and early lesion formation through the inhibition of MAPK7 signaling. The Journal of pathology 31 30565701
2019 Chronic hyperglycemia regulates microglia polarization through ERK5. Aging 31 30684443
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
2023 An ERK5-NRF2 Axis Mediates Senescence-Associated Stemness and Atherosclerosis. Circulation research 29 37264926
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
2014 The role of ERK5 in endothelial cell function. Biochemical Society transactions 29 25399574
2005 Control of body size by SMA-5, a homolog of MAP kinase BMK1/ERK5, in C. elegans. Development (Cambridge, England) 29 15944183
2018 MicroRNA-143 targets ERK5 in granulopoiesis and predicts outcome of patients with acute myeloid leukemia. Cell death & disease 28 30050105
2017 Rare coding variants in MAPK7 predispose to adolescent idiopathic scoliosis. Human mutation 28 28714182
2022 The ERK5/NF-κB signaling pathway targets endometrial cancer proliferation and survival. Cellular and molecular life sciences : CMLS 27 36123565
2020 CircRNA Circ_0001721 Promotes the Progression of Osteosarcoma Through miR-372-3p/MAPK7 Axis. Cancer management and research 27 32982424
2015 MAPK7 gene controls proliferation, migration and cell invasion in osteosarcoma. Molecular carcinogenesis 27 26460937
2014 Ubiquitin-dependent regulation of MEKK2/3-MEK5-ERK5 signaling module by XIAP and cIAP1. The EMBO journal 27 24975362
2013 X-ray crystal structure of ERK5 (MAPK7) in complex with a specific inhibitor. Journal of medicinal chemistry 27 23656407
2011 ERK1/2 and ERK5 have distinct roles in the regulation of brain-derived neurotrophic factor expression. Journal of neuroscience research 27 21647938
2009 ERK5 activation enhances mesangial cell viability and collagen matrix accumulation in rat progressive glomerulonephritis. American journal of physiology. Renal physiology 27 19846573
2022 Clinical Significance and Regulation of ERK5 Expression and Function in Cancer. Cancers 26 35053510
2017 Targeting BMK1 Impairs the Drug Resistance to Combined Inhibition of BRAF and MEK1/2 in Melanoma. Scientific reports 26 28387310
2011 Targeting the BMK1 MAP kinase pathway in cancer therapy. Clinical cancer research : an official journal of the American Association for Cancer Research 26 21385929
2022 ERK5 Signalling and Resistance to ERK1/2 Pathway Therapeutics: The Path Less Travelled? Frontiers in cell and developmental biology 25 35903549
2021 Molecular Mechanisms of Epithelial to Mesenchymal Transition Regulated by ERK5 Signaling. Biomolecules 25 33572742
2020 Small molecule ERK5 kinase inhibitors paradoxically activate ERK5 signalling: be careful what you wish for…. Biochemical Society transactions 25 32915196
2017 Role of AP-2α and MAPK7 in the regulation of autocrine TGF-β/miR-200b signals to maintain epithelial-mesenchymal transition in cholangiocarcinoma. Journal of hematology & oncology 25 29084594
2015 miR-429 inhibits glioma invasion through BMK1 suppression. Journal of neuro-oncology 24 26272601
2015 ERK5/HDAC5-mediated, resveratrol-, and pterostilbene-induced expression of MnSOD in human endothelial cells. Molecular nutrition & food research 24 26443543
2023 Aerobic Exercise Alters the Melanoma Microenvironment and Modulates ERK5 S496 Phosphorylation. Cancer immunology research 23 37307577
2018 IFN-γ-inducible antiviral responses require ULK1-mediated activation of MLK3 and ERK5. Science signaling 23 30459284
2008 ERK5 regulation in naïve T-cell activation and survival. European journal of immunology 23 18792406
2018 Fluid shear stress promotes osteoblast proliferation through the NFATc1-ERK5 pathway. Connective tissue research 22 29609502