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Showing MAP3K2 — MEKK2 is a alias.

MAP3K2

Mitogen-activated protein kinase kinase kinase 2 · UniProt Q9Y2U5

Length
619 aa
Mass
69.7 kDa
Annotated
2026-06-10
100 papers in source corpus 46 papers cited in narrative 47 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 8/9 claims corpus-supported (89%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAP3K2 (MEKK2) is a serine/threonine MAP3 kinase that functions as a central signaling node coupling diverse receptor inputs to multiple downstream MAPK and non-MAPK pathways (PMID:11073940, PMID:14978743). Its activation requires dimerization through a surface centered on the catalytic αG helix and C-terminal activation segment, which drives autophosphorylation and substrate phosphorylation (PMID:15695508, PMID:41318559); this same structural surface specifies substrate selectivity, recruiting MEK5 through the PB1 domain to activate ERK5 and recruiting MKK6/MKK7 through the αG helix to activate stress kinases (PMID:12912994, PMID:17452462, PMID:41318559). Through PB1 domain–mediated heterodimerization with MEK5, MEKK2 activates the MEK5–ERK5 module, while through MKK7/MKK4 it activates JNK and AP-1–driven cytokine gene expression (PMID:12912994, PMID:17452462, PMID:12659851). Upstream, MEKK2 is engaged by WNK1, Rap1 (downstream of BDNF), and growth-factor and cytokine receptors including FGF-2, EGF, IgE, c-Kit, and TLR receptors, with EGF triggering its cytosol-to-nucleus translocation to access nuclear MEK5–ERK5 (PMID:11032806, PMID:15075238, PMID:14681216, PMID:17003042). Activation-loop phosphorylation at Ser519 is a key regulatory event induced in a TRAF6-dependent manner and required for TLR-induced IL-6 production, while phosphorylation at Thr283 and 14-3-3 binding restrain trans-autophosphorylation and kinase activity (PMID:16362041, PMID:23963453). MEKK2 abundance is tightly controlled by ubiquitin-mediated degradation through multiple E3 ligases—Smurf1 (facilitated by STK38/NDR2), CHIP, XIAP/cIAP1, and NEDD4L—which terminate ERK, ERK5, and NF-κB signaling and couple receptor signaling to defined cellular outcomes (PMID:15820682, PMID:20588253, PMID:24975362, PMID:25981615, PMID:36161689, PMID:30504095). Beyond the MAPK cascades, MEKK2 phosphorylates non-canonical substrates to regulate WNT/bone formation (β-catenin S675, promoting USP15-mediated stabilization), Hedgehog signaling (GLI1, reducing its stability and DNA binding), Hippo signaling (LATS1/2 and YAP/TAZ), myeloid ROS production (p47phox S208), and STK38 stability (S91) (PMID:26884171, PMID:29662197, PMID:33571521, PMID:31690749, PMID:33910977). These activities place MEKK2 at the intersection of immune cell signaling, osteoblast/skeletal biology, intestinal stem-cell maintenance, vascular integrity, and cancer cell invasion, the last potentiated by SMYD3 methylation at K260 that blocks PP2A binding (PMID:24847881, PMID:33658717, PMID:37203562, PMID:37976356). A crystal structure of the kinase domain provides a structural basis for dimerization-driven activation and differential substrate recruitment (PMID:41318559).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1999 Medium

    Established MEKK2 as a TCR-responsive kinase that physically relocalizes to the immunological synapse, linking it to early antigen receptor signaling.

    Evidence Live-cell imaging and dominant-negative MEKK2 in T cell/APC conjugates

    PMID:10549623

    Open questions at the time
    • Direct substrates at the synapse not defined
    • Dominant-negative approach does not establish endogenous requirement
  2. 2000 High

    Identified MEK5 as a direct MEKK2 partner and ERK5 as a downstream output, and showed MEKK2 is genetically required for receptor-induced JNK activation and cytokine transcription, defining its dual MAPK outputs.

    Evidence Yeast two-hybrid, dominant-negative epistasis, and MEKK2-deficient mast cells

    PMID:11032806 PMID:11073940

    Open questions at the time
    • Molecular basis of MEK5 binding not yet resolved
    • How a single MAP3K selects ERK5 vs JNK output unclear
  3. 2002 High

    Genetic knockout revealed MEKK2 negatively regulates TCR signaling strength, showing its role is not uniformly activating but context-dependent.

    Evidence Mekk2 KO mice; T cell proliferation, cytokine, and MAPK activation assays

    PMID:12138187

    Open questions at the time
    • Mechanism of negative regulation in T cells not defined
    • JNK only moderately affected, leaving redundancy unexplained
  4. 2003 High

    Defined the PB1 domain as the structural module mediating selective MEK5/ERK5 pathway engagement and placed WNK1 upstream as a MEKK2-activating kinase.

    Evidence PB1 domain binding/mutation assays; WNK1 Co-IP, in vitro kinase, and dominant-negative epistasis

    PMID:12912994 PMID:14681216

    Open questions at the time
    • PB1-independent substrate routing not yet addressed
    • WNK1 phospho-site on MEKK2 not mapped
  5. 2004 High

    Established MEKK2 as the FGF-2/EGF receptor coupler that coordinately drives ERK5 and JNK and undergoes signal-induced nuclear translocation to reach nuclear MEK5.

    Evidence MEKK2-/- MEFs with stimulus specificity; subcellular fractionation and live-cell imaging; FLS in vitro kinase assays

    PMID:14734742 PMID:14978743 PMID:15075238

    Open questions at the time
    • Trigger for nuclear import not molecularly defined
    • MKK4 vs MKK7 selectivity not resolved
  6. 2005 High

    Resolved the activation logic: dimerization through the catalytic domain drives activation, Ser519 in the activation loop is the critical regulatory phospho-site (TRAF6-dependent), and Smurf1 and Mip1 act as negative regulators by degradation and dimer blockade respectively.

    Evidence Chemical-induced dimerization, deletion mapping, S519A mutagenesis with phospho-antibody, Smurf1-deficient mice, Mip1 Co-IP/siRNA

    PMID:15695508 PMID:15820682 PMID:15988011 PMID:16362041

    Open questions at the time
    • Kinase responsible for Ser519 phosphorylation in vivo not fully defined
    • Mip1 mechanism characterized in a single lab
  7. 2007 High

    Defined how the PB1 domain partitions MEKK2 output—front-to-back PB1 binding to MEK5 drives ERK5 while a C-terminal acidic cluster routes activated MEKK2 to MKK7/JNK—providing a molecular switch for substrate choice.

    Evidence PB1 residue mutagenesis, Co-IP, and ERK5/JNK kinase activation assays

    PMID:17452462

    Open questions at the time
    • Conformational change driving the switch not visualized
    • Quantitative balance between outputs in vivo not measured
  8. 2010 High

    Showed MEKK2 turnover is functionally instructive: CHIP-mediated degradation enforces transient ERK kinetics required for correct aquaporin gene induction, and Lad1/calcium controls EGF-induced MEKK2 nuclear translocation.

    Evidence CHIP Co-IP/siRNA/gene targeting with ERK time-course and AQP readout; Lad1 Co-IP and calcium-modifier translocation imaging

    PMID:20588253 PMID:20830310

    Open questions at the time
    • Generality of CHIP regulation beyond osmotic stress unknown
    • Lad1 findings from a single lab
  9. 2011 High

    Extended MEKK2 function to TGF-β/SMAD signaling, showing it phosphorylates SMAD2/3 linker regions to restrain Treg/Th17 differentiation, a non-classical MAPK output with immunological consequence.

    Evidence Conditional/constitutive Map3k2/Map3k3 KO mice, in vitro differentiation, phospho-SMAD linker blots, EAE model

    PMID:21333552

    Open questions at the time
    • Direct vs indirect SMAD linker phosphorylation not fully separated
    • Redundancy with MEKK3 limits MEKK2-specific attribution
  10. 2014 High

    Identified SMYD3 K260 methylation as a positive regulator that blocks PP2A binding to sustain Ras/ERK signaling, and expanded the E3 ligase repertoire (XIAP/cIAP1 via K63 chains competing with MEK5) and focal-adhesion functions controlling cell migration.

    Evidence Protein array, in vitro methylation, PP2A Co-IP, tumor mouse models; K63 chain analysis and trimeric complex reconstitution; paxillin Co-IP/ubiquitylation and FA imaging

    PMID:24491810 PMID:24847881 PMID:24975362 PMID:25190348

    Open questions at the time
    • Phosphatase(s) reversing K260 methylation context not detailed
    • Focal-adhesion substrate(s) beyond paxillin unclear
  11. 2016 High

    Broadened MEKK2 substrate scope to developmental pathway control—β-catenin S675 phosphorylation promoting USP15-mediated stabilization in bone, and GLI1 phosphorylation suppressing Hedgehog—linking it to WNT and Hh signaling.

    Evidence MEKK2-deficient mice, in vitro kinase with phospho-site mapping, USP15/SUFU Co-IP, genetic epistasis; SMYD3-MEKK2 co-crystal with inhibitor design

    PMID:26884171 PMID:27066749 PMID:29662197

    Open questions at the time
    • Receptor inputs upstream of β-catenin/GLI1 phosphorylation incompletely defined
    • GLI1 findings rest on a single lab
  12. 2021 High

    Demonstrated tissue-protective and physiological roles: a ROS-MEKK2-ERK5-KLF2 axis maintaining intestinal stem cells, p47phox S208 phosphorylation controlling myeloid ROS in lung injury, and MEKK2/3 activation of LATS1/2-YAP/TAZ in the Hippo pathway downstream of TNF.

    Evidence Genetic mouse models with injury/ALI/colitis assays, single-cell profiling, in vitro kinase assays, STRIPAK interaction studies

    PMID:32737854 PMID:33571521 PMID:33658717 PMID:33910977

    Open questions at the time
    • Direct vs indirect LATS/YAP phosphorylation not fully separated from MEKK3
    • Upstream activator of the intestinal ROS axis not pinpointed
  13. 2023 High

    Connected MEKK2 stability control to vascular disease, showing Best3 binding inhibits Ser153 phosphorylation and promotes MEKK2/3 turnover, with loss driving aortic dissection, and extended SMYD3 methylation to prostate cancer EMT.

    Evidence Co-IP/MS, Best3 smooth-muscle KO mice, phospho/ubiquitination assays; SMYD3 inhibition and xenografts with EMT markers

    PMID:37203562 PMID:37976356

    Open questions at the time
    • Kinase phosphorylating Ser153 not identified
    • Causal substrate downstream of stabilized MEKK2 in dissection unclear
  14. 2025 High

    Provided the definitive structural basis for activation and substrate selectivity: an αG helix–centered dimerization surface drives autophosphorylation, with MEK5 recruited via PB1 and MKK6 via the αG surface independently of PB1.

    Evidence 2.4 Å crystal structure with αG surface mutagenesis and in vitro substrate phosphorylation assays

    PMID:41318559

    Open questions at the time
    • Structure of full-length regulated MEKK2 not solved
    • How upstream phosphorylation reshapes the dimer interface unresolved

Open questions

Synthesis pass · forward-looking unresolved questions
  • How the many parallel regulatory inputs (methylation, multiple phospho-sites, competing E3 ligases, and scaffold/adaptor binding) are integrated to set MEKK2 output toward a specific pathway in a given cell type remains unresolved.
  • No unified quantitative model of input integration
  • MEKK2 vs MEKK3 division of labor across tissues not systematically mapped
  • Cell-type-specific substrate prioritization mechanism unknown

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:0060089 molecular transducer activity 3 GO:0140657 ATP-dependent activity 2
Localization
GO:0005634 nucleus 2 GO:0005856 cytoskeleton 2 GO:0005829 cytosol 1
Pathway
R-HSA-168256 Immune System 7 R-HSA-162582 Signal Transduction 6 R-HSA-392499 Metabolism of proteins 5 R-HSA-1266738 Developmental Biology 3
Partners
MAP2K5MAP2K7NEDD4LSMURF1STK38STUB1WNK1XIAP
Complex memberships
MEKK2/3–XIAP/cIAP1–MEK5 trimeric complexMEKK2–MEK5 PB1 complex

Evidence

Reading pass · 47 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 SMYD3 methylates MAP3K2 at lysine 260, potentiating activation of the Ras/Raf/MEK/ERK signaling module. Methylation of MAP3K2 at K260 blocks binding of the PP2A phosphatase complex to MAP3K2, preventing PP2A-mediated negative regulation of the MAP kinase pathway. Protein array technology to identify MAP3K2 as SMYD3 substrate; in vitro methylation assays; Co-IP showing PP2A-MAP3K2 interaction blocked by methylation; mouse models of pancreatic/lung adenocarcinoma Nature High 24847881
2005 Smurf1, a HECT domain ubiquitin E3 ligase, physically interacts with MEKK2 and promotes its ubiquitination and proteasomal degradation, thereby suppressing osteoblast activity and JNK signaling downstream of BMP. Co-IP showing Smurf1-MEKK2 physical interaction; ubiquitination assays; Smurf1-deficient mouse model showing accumulation of phosphorylated MEKK2 and enhanced JNK activation Cell High 15820682
2003 The PB1 domains of MEKK2 and MEKK3 heterodimerize with the PB1 domain of MEK5, forming a complex required for ERK5 pathway activation. Deletion or mutation of the MEKK2 PB1 domain abolishes MEKK2-MEK5 complex formation and ERK5 activation. The PB1 domain interaction is specific to the ERK5 pathway and does not affect p38 or JNK pathways. In vitro PB1 domain binding assays; co-immunoprecipitation of MEKK2 and MEK5 from cell lysates; deletion/mutation analysis; dominant-negative expression experiments The Journal of biological chemistry High 12912994
2000 MEKK2 activates the MEK5-BMK1/ERK5 pathway; MEK5 was identified as a binding partner of MEKK2 by yeast two-hybrid screening, and a dominant-negative MEK5 blocked ERK5 activation by MEKK2. MEKK2 also associates with the T cell adapter protein Lad/RIBP, and co-localizes with Lad/RIBP at the T cell/APC contact site during T cell activation. Yeast two-hybrid library screen; co-localization imaging; dominant-negative expression; kinase activity assays The Journal of biological chemistry High 11073940
2000 MEKK2 is required for receptor-mediated JNK activation and cytokine gene transcription in mast cells following IgE receptor or c-Kit ligation. MEKK2-deficient ES cell-derived mast cells show markedly reduced cytokine production and loss of receptor-mediated JNK activation, while JNK activation by UV irradiation is unaffected. Targeted gene disruption of MEKK2 in ES cell-derived mast cells; RT-PCR for cytokine transcription; kinase assays for JNK activation The EMBO journal High 11032806
2004 MEKK2 coordinately activates ERK5 and JNK pathways in response to FGF-2 signaling in fibroblasts. MEKK2-deficient MEFs lose ERK5 and JNK activation in response to FGF-2 but not LPS or TNFα, demonstrating MEKK2 specificity in FGF-2 receptor signaling. MEKK2 regulates AP-1 activity by controlling expression of c-Jun, Fra-1, and Fra-2 and c-Jun N-terminal phosphorylation, leading to cytokine gene expression. MEKK2-/- mouse embryonic fibroblasts; kinase activation assays; RT-PCR for AP-1 components and cytokines Journal of cellular physiology High 14978743
2004 MEKK2 is localized mainly in the cytosol of resting cells and translocates to the nucleus upon EGF stimulation, allowing transmission of signals to nuclear MEK5. MEK5 and ERK5 are constitutively nuclear in endogenous form, bound to detergent-resistant nuclear moieties. Immunocytochemistry; live cell fluorescence imaging; in situ detergent extraction; subcellular fractionation Journal of cell science Medium 15075238
2005 MEKK2 activation requires dimerization through its catalytic domain. The dimerization motif maps to the catalytic domain (N-terminal region not required). Inactive, non-phosphorylated MEKK2 forms more dimers than phosphorylated active MEKK2. Prevention of dimerization inhibits MEKK2-mediated JNK activation; chemical-induced dimerization augments JNK activation and AP-1 reporter activity. Dimerization mapping using deletion constructs; chemical-induced dimerization system; JNK activation assays; AP-1 reporter gene assays The Journal of biological chemistry High 15695508
2005 Mip1 (MEKK2-interacting protein) forms a complex with inactive, non-phosphorylated MEKK2 and prevents MEKK2 activation by blocking MEKK2 dimer formation, thereby inhibiting JNK1, ERK5, and AP-1 activation. The endogenous Mip1-MEKK2 complex dissociates transiently following EGF stimulation. siRNA knockdown of Mip1 augments MEKK2-mediated JNK and AP-1 activation. Co-IP; siRNA knockdown; kinase and reporter gene activation assays Molecular and cellular biology Medium 15988011
2005 Serine 519 in MEKK2 (and S526 in MEKK3) is a key regulatory phosphorylation site required for kinase activation. Mutation of S519 to alanine severely impairs MEKK2 activation. LPS induces phosphorylation of this serine in a TRAF6-dependent manner, and this phosphorylation is required for TLR-induced IL-6 production. Site-directed mutagenesis (S519A); anti-phospho-MEKK2/3 antibody; LPS stimulation assays; TRAF6 perturbation The EMBO journal High 16362041
2003 WNK1 activates ERK5 via MEKK2 and MEKK3 in an MEKK2/3-dependent mechanism. WNK1 phosphorylates MEKK2 and MEKK3 in vitro and activates MEKK3 in cells. Both MEKK2 and MEKK3 co-immunoprecipitate with endogenous WNK1. Dominant-negative MEKK2 and MEKK3 block WNK1-induced ERK5 activation. Co-IP of WNK1 with MEKK2/3; in vitro kinase assay; dominant-negative expression; siRNA knockdown of WNK1 The Journal of biological chemistry High 14681216
1999 MEKK2 translocates to the T cell/antigen-presenting cell interface upon antigen-mediated TCR engagement. Biochemical activation of MEKK2 follows TCR stimulation, and dominant-negative MEKK2 inhibits TCR-mediated conjugate stabilization and ERK/p38 MAPK phosphorylation. Live cell fluorescence imaging; immunocytochemistry; dominant-negative expression; kinase activation assays Immunity Medium 10549623
2002 MEKK2-deficient T cells show augmented proliferation and increased IL-2/IFNγ production in response to anti-CD3 stimulation, and greater susceptibility to anti-CD3-induced cell death, indicating MEKK2 negatively regulates TCR signaling strength. TCR-mediated JNK activation was moderately enhanced (not abolished) in MEKK2-/- T cells; ERK and p38 activation were unaffected. Targeted Mekk2 gene disruption in mice; T cell proliferation assays; cytokine production assays; JNK/ERK/p38 activation assays Molecular and cellular biology High 12138187
2006 BDNF activates ERK5 in cortical neurons via a Rap1-MEKK2 signaling cascade. BDNF activates Rap1, which activates MEKK2 (a MEK5 kinase); inhibition of either Rap1 or MEKK2 attenuates BDNF-induced ERK5 activation. Ras and MEKK3 do not play significant roles in this neuronal BDNF-ERK5 pathway. Dominant-negative and constitutively active expression of Rap1 and MEKK2; kinase activity assays in cortical neurons The Journal of biological chemistry Medium 17003042
2010 CHIP (carboxyl terminus of Hsc70-interacting protein) E3 ubiquitin ligase binds MEKK2 and promotes its degradation, thereby terminating ERK activation in response to hyperosmotic stress. Transient ERK activation via MEKK2 is required for proper aquaporin (AQP1, AQP5) gene induction; CHIP depletion prolongs MEKK2 stability, prolongs ERK activity, and paradoxically suppresses AQP gene expression. Co-IP identifying CHIP-MEKK2 interaction; siRNA knockdown of CHIP; gene targeting of CHIP; ERK activity time-course assays; AQP gene expression assays The EMBO journal High 20588253
2007 MEKK2 and MEK5 PB1 domains interact in a front-to-back arrangement; quiescent MEKK2 preferentially binds MEK5 via PB1, leading to ERK5 activation. Upon activation, MEKK2 binds and activates MKK7 via the C-terminal acidic cluster of the MEKK2 PB1 domain, leading to JNK activation. The C-terminal MEK5 PB1 extension encodes an ERK5 docking site required for MEK5 activation of ERK5. Mutagenesis of PB1 domain residues; co-immunoprecipitation; kinase activation assays for ERK5 and JNK Molecular and cellular biology High 17452462
2004 MEKK2 immunoprecipitates from IL-1-stimulated fibroblast-like synoviocytes (FLS) show increased phosphorylation of MKK4 and MKK7 (the MAP2Ks that activate JNK), and MEKK2 activates c-Jun in an IL-1-dependent manner inhibitable by the JNK inhibitor SP600125. In vitro kinase assays using MEKK2 immunoprecipitates; Western blot; pharmacological inhibition with SP600125 Journal of immunology Medium 14734742
2011 MEKK2 and MEKK3 (acting in T cells) negatively regulate TGF-β-mediated Th cell differentiation. Map3k2-/-Map3k3Lck-Cre/- T cells show impaired phosphorylation of SMAD2 and SMAD3 at their linker regions, leading to enhanced Treg and Th17 differentiation in response to TGF-β. Conditional and constitutive genetic knockout mice; in vitro T cell differentiation assays; phospho-SMAD2/3 linker region Western blot; EAE disease model Immunity High 21333552
2008 XIAP physically interacts with MEKK2 and ubiquitinates MEKK2 (in an E3 ligase-dependent manner) following TNFα stimulation, regulating a second wave of NF-κB activation. Co-IP showing XIAP-MEKK2 interaction; ubiquitination assays; NF-κB reporter assays Cellular signalling Medium 18761086
2014 XIAP and cIAP1 directly interact with MEKK2/3, compete with PB1 domain-mediated MEK5 binding, and conjugate predominantly K63-linked ubiquitin chains to MEKK2 and MEKK3, which directly impede MEK5-ERK5 interaction in a trimeric complex, leading to ERK5 inactivation. Loss of XIAP causes hyperactivation of ERK5 and promotes myoblast differentiation in a MEKK2/3-ERK5-dependent manner. Co-IP; ubiquitin chain linkage analysis (K63); in vitro reconstitution of trimeric complex; loss-of-function by multiple strategies; myoblast differentiation assays The EMBO journal High 24975362
2016 MEKK2 mediates an alternative noncanonical pathway for β-catenin activation in osteoblasts downstream of FGF2. FGF2 activates MEKK2 to phosphorylate β-catenin at serine 675, promoting recruitment of the deubiquitinase USP15, which prevents β-catenin ubiquitination and proteasomal degradation, thereby enhancing WNT signaling and bone formation. MEKK2-deficient mice; in vitro kinase assays; phospho-site mapping (S675); USP15 Co-IP; genetic interaction studies between Mekk2 and β-catenin null alleles Proceedings of the National Academy of Sciences of the United States of America High 26884171
2013 MEKK2 is regulated by phosphorylation-dependent association with 14-3-3 proteins. Phosphorylation of MEKK2 at Thr-283 results in decreased activation loop phosphorylation at Ser-519 and reduced kinase activity. In the absence of 14-3-3 binding, inactive MEKK2 undergoes trans-autophosphorylation at Ser-519; enforced 14-3-3 binding reduces this trans-autophosphorylation. T283A MEKK2 shows enhanced stress-activated JNK activity but reduced ERK activation. Site-directed mutagenesis (T283A); 14-3-3 association assays; phosphorylation assays; expression in MEKK2-/- background; IL-6 and proliferation assays The Journal of biological chemistry Medium 23963453
2015 Stk38 kinase constitutively associates with the ubiquitin E3 ligase Smurf1 and facilitates Smurf1-mediated MEKK2 ubiquitination and degradation. MEKK2 is required for CpG/TLR9-induced ERK1/2 activation, TNF-α and IL-6 production in macrophages, but not for LPS-induced cytokine production. Stk38 deficiency increases CpG-induced ERK1/2 activation and inflammatory cytokine production. Co-IP showing Stk38-Smurf1 association; ubiquitination assays; MEKK2-/- macrophage function assays; Stk38-deficient mice; bacterial infection model Nature communications High 25981615
2018 Kir2.1 (inwardly rectifying K+ channel) interacts with STK38 to inhibit Smurf1-mediated ubiquitination and degradation of MEKK2, thereby activating the MEKK2-MEK1/2-ERK1/2-Snail pathway to promote EMT and invasion in gastric cancer cells. This function is independent of potassium ion permeation. Co-IP; siRNA knockdown; ubiquitination assays; cell invasion and metastasis assays Cancer research Medium 29549164
2014 MEKK2 associates with the LD1 motif of paxillin at focal adhesion complexes upon cell attachment to fibronectin. MEKK2 induces paxillin ubiquitylation in a manner requiring both the paxillin LD1 motif and MEKK2 kinase activity, and promotes paxillin redistribution from focal adhesions to the cytoplasm without promoting paxillin degradation. Co-IP; ubiquitylation assays; MEKK2 knockdown; focal adhesion imaging; fibronectin attachment assays The Biochemical journal Medium 25190348
2014 Silencing MEKK2 expression in invasive breast tumor cells enhances cell spread area and focal adhesion stability while reducing cell migration. Cell attachment to fibronectin or Matrigel induces MEKK2 activation and localization to focal adhesions. MEKK2 ablation enhances focal adhesion size and frequency, inhibits fibronectin-induced ERK5 signaling, and inhibits FAK autophosphorylation. siRNA knockdown; focal adhesion imaging; kinase activation assays; focal adhesion turnover assays Biochimica et biophysica acta Medium 24491810
2016 MEKK2 and MEKK3 suppress Hedgehog pathway activity by phosphorylating GLI1 at multiple Ser/Thr sites, reducing GLI1 protein stability, DNA-binding ability, and increasing GLI1 association with SUFU. MEKK2/3 mediate FGF2-induced inhibition of Hh signaling. In vitro kinase assays; phospho-site mapping; protein stability assays; DNA-binding assays; SUFU Co-IP; medulloblastoma cell proliferation assays Oncogene Medium 29662197
2003 Mutations in kinase subdomain X of MEKK2 impair phosphorylation of MAP2Ks MKK7 and MEK5, abolish activation of JNK1 and ERK5, and diminish AP-1 reporter activation. The spectrum of subdomain X mutations affecting MEKK2 is overlapping but not identical to those affecting MEKK1. Site-directed mutagenesis of subdomain X residues; in vitro kinase assays; JNK/ERK5 activation assays; AP-1 reporter assays Biochemical and biophysical research communications Medium 12659851
2010 EGF-induced MEKK2 binding to the adaptor protein Lad1 requires a proper calcium concentration, and calcium modifiers that reduce MEKK2-Lad1 interaction also inhibit EGF-induced MEKK2 nuclear translocation and ERK5 activation. Lad1 interaction is required for full tyrosine phosphorylation of MEKK2. Co-immunoprecipitation; in vitro binding assays; calcium modifier experiments; nuclear translocation imaging PloS one Medium 20830310
2021 MAP3K2 mediates a ROS-MAP3K2-ERK5-KLF2 signaling axis in intestinal stromal cells (MRISCs) to enhance R-spondin 1 production following intestinal injury, thereby maintaining LGR5+ intestinal stem cells and protecting against acute intestinal damage. MAP3K2-specific genetic studies; single-cell transcriptomics; epigenetic profiling; functional intestinal injury models in mice; R-spondin 1 production assays Nature High 33658717
2021 MEKK2 and MEKK3 activate LATS1/2 and inhibit YAP/TAZ activity (Hippo pathway) downstream of TNF signaling, acting in parallel to MST1/2 and MAP4Ks. MEKK2/3 directly interact with LATS1/2 and YAP/TAZ and phosphorylate them. The STRIPAK complex associates with MEKK3 via CCM2/CCM3 to inactivate MEKK3, and upstream Hippo signals trigger MEKK3 dissociation from STRIPAK. Co-IP showing MEKK2/3-LATS1/2-YAP/TAZ interactions; in vitro phosphorylation assays; epistasis experiments; STRIPAK complex interaction studies The Journal of biological chemistry Medium 33571521
2016 Co-crystal structure of SMYD3 with a MEKK2 peptide substrate was determined, revealing how SMYD3 engages MAP3K2. SMYD3 follows a partially processive methylation mechanism. Structure-based design yielded GSK2807, a SAM-competitive inhibitor (Ki = 14 nM) that bridges the SAM-binding pocket and MEKK2 substrate lysine tunnel. Co-crystal structure of SMYD3-MEKK2 peptide; kinetic characterization; structure-based inhibitor design Structure High 27066749
2020 MEKK2 mediates aberrant ERK activation downstream of NF1 loss in osteoblasts via a noncanonical ERK pathway. Mekk2-/- mice with NF1 conditional deletion (Nf1fl/fl;Mekk2-/-;Dmp1-Cre) show amelioration of NF1-associated skeletal phenotypes, placing MEKK2 downstream of NF1 in this ERK activation pathway. Genetic epistasis using Nf1 conditional and Mekk2 constitutive knockouts; skeletal phenotype analysis; ERK activation assays Nature communications High 33177525
2012 MEKK2 regulates right ventricular hypertrophy in hypoxia-induced pulmonary hypertension, in part through regulation of ERK5 abundance and phosphorylation. MEKK2-/- mice show attenuated RV hypertrophy and selective inhibition of inflammatory gene expression compared to WT mice under chronic hypoxia. MEKK2-/- mice; chronic hypobaric hypoxia model; RV hypertrophy measurements; ERK5 phosphorylation assays; gene expression analysis American journal of physiology. Heart and circulatory physiology Medium 23125215
2022 NEDD4L (HECT-type E3 ligase) constitutively and directly binds MEKK2 and promotes its poly-ubiquitination and degradation, negatively regulating signaling induced by TNF-α, IL-1, and IL-17. In IL-17R signaling, IL-17-induced MEKK2 Ser520 phosphorylation is required both for downstream p38 and NF-κB activation and for NEDD4L-mediated MEKK2 degradation. Co-IP; ubiquitination assays; NEDD4L knockdown/deficiency; Nedd4l-deficient mice; EAE model EMBO reports High 36161689
2019 MEKK2 phosphorylates STK38 at Ser91, protecting STK38 from calpain-mediated cleavage. MEKK2 knockdown enhances hyperthermia-induced degradation of STK38. A phosphorylation-defective S91A STK38 mutant is susceptible to calpain degradation, demonstrating that MEKK2-mediated phosphorylation at Ser91 is required for STK38 stability. In vitro MEKK2 kinase assay with phospho-site identification; phospho-defective mutant (S91A); MEKK2 knockdown; calpain inhibitor experiments Scientific reports Medium 31690749
2016 MEKK2 promotes GLI1 phosphorylation on multiple Ser/Thr sites, reducing its protein stability, DNA-binding ability, and increasing SUFU association, thereby suppressing Hedgehog pathway activity. MEKK2 mediates FGF2-induced inhibition of Hh signaling. In vitro phosphorylation assays; protein stability assays; DNA-binding assays; SUFU Co-IP Oncogene Medium 29662197
2018 NDR2 kinase interacts with Smurf1 E3 ligase and promotes Smurf1-mediated K48-linked ubiquitination of MEKK2, leading to MEKK2 degradation and inhibition of IL-17-induced MAPK and NF-κB activation and inflammatory cytokine production. Co-IP showing NDR2-Smurf1 interaction; ubiquitination assay (K48 linkage); NDR2 and Smurf1 knockdown; IL-17-induced cytokine assays Molecular immunology Medium 30504095
2021 MAP3K2-mediated Th1 cell differentiation in the intestine is regulated by IL-18 and requires specific JNK activation. MAP3K2-deficient naïve CD4+ T cells have a reduced ability to induce colitis in a T cell transfer model, with fewer IFN-γ-producing cells in intestines. T cell transfer colitis model; MAP3K2-deficient T cells; in vitro differentiation conditions; cytokine measurement; JNK activation assays Science China. Life sciences Medium 32737854
2001 A single amino acid difference between MEKK2 (Val384) and MEKK3 (Ser390), immediately N-terminal to the active site lysine in kinase domain II/III, determines differential in vitro kinase activity in Triton X-100 detergent. Mutation of MEKK3 S390V confers activity in Triton X-100; the reciprocal MEKK2 V384S mutation abolishes activity in Triton X-100. Chimeric kinase constructs; site-directed mutagenesis; in vitro kinase assays in two detergents Biochimica et biophysica acta Medium 11343802
2023 Best3 interacts with both MEKK2 and MEKK3 in vascular smooth muscle cells, and this interaction inhibits phosphorylation of MEKK2 at serine 153. Best3 deficiency induces phosphorylation-dependent stabilization of MEKK2/3 (inhibiting ubiquitination and turnover), thereby activating downstream MAPK signaling and triggering aortic dissection. Co-immunoprecipitation coupled with mass spectrometry; Best3 smooth muscle cell-specific KO mice; phosphorylation assays; ubiquitination assays; single-cell RNA sequencing; proteomics Circulation High 37203562
2025 Crystal structure of the MEKK2 kinase domain (2.4 Å) in complex with ponatinib reveals that MEKK2 dimerizes via a surface centered on the αG helix and C-terminal activation segment. This surface is required for MEKK2 autophosphorylation and for phosphorylation of both MEK5 and MKK6. MEK5 recruitment is PB1 domain-dependent, while MKK6 recruitment is αG helix-dependent (PB1-independent), providing a structural basis for substrate selectivity. 2.4 Å crystal structure; site-directed mutagenesis of αG helix surface; autophosphorylation assays; in vitro substrate phosphorylation assays (MEK5, MKK6); Co-IP/dimerization assays Nature communications High 41318559
2023 SMYD3-dependent methylation of MAP3K2 promotes epithelial-mesenchymal transition behaviors in prostate cancer cells by altering the abundance of vimentin, and supports a positive feedback loop maintaining high SMYD3 levels. SMYD3 inhibitor treatment; siRNA knockdown; xenograft mouse models; EMT marker analysis; vimentin abundance measurement Science advances Medium 37976356
2021 MAP3K2-mediated phosphorylation of NADPH oxidase 2 subunit p47phox at Ser208 increases ROS formation in myeloid cells. Genetic inactivation of MAP3K2 and MAP3K3 in myeloid cells or hematopoietic S208A mutation of p47phox attenuates acute lung injury and abrogates the protective effects of pazopanib. In vitro phosphorylation assays; myeloid-specific MAP3K2/3 conditional KO mice; p47phox S208A knockin mice; ALI models; pazopanib pharmacology Science translational medicine High 33910977
2016 PDGF-BB-induced ERK5 activation in smooth muscle cells is dependent on Mekk2 (and Mek1/2, Mek5, PI3-kinase, and PKC), suggesting close co-regulation between ERK1/2 and ERK5 MAP kinase pathways downstream of PDGFR. Dominant-negative expression of Mekk2; kinase inhibitor studies; ERK5 activation assays in MOVAS smooth muscle cells Cellular signalling Low 27339033
2016 Sublytic C5b-9 induces MEKK2 phosphorylation at Ser153, Ser164, and Ser239, which is necessary for p38 MAPK activation, leading to the MEKK2-p38 MAPK-IRF-1-TRADD-caspase 8 apoptotic cascade in glomerular mesangial cells. Phosphorylation site identification; site-directed mutagenesis; siRNA knockdown; in vitro kinase assays; in vivo Thy-1 nephritis rat model Journal of immunology Medium 28039298
2015 Interaction of paxillin LD1 motif with the MEKK2 amino-terminal region relieves MEKK2 auto-inhibition: recombinant paxillin induces MEKK2 auto-phosphorylation in vitro, and paxillin knockdown reduces MEKK2 activity in cells. In vitro auto-phosphorylation assay with recombinant paxillin; siRNA-mediated paxillin knockdown; LD1 motif binding assays Journal of molecular signaling Medium 27096002

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2014 SMYD3 links lysine methylation of MAP3K2 to Ras-driven cancer. Nature 319 24847881
2005 Ubiquitin ligase Smurf1 controls osteoblast activity and bone homeostasis by targeting MEKK2 for degradation. Cell 311 15820682
2003 WNK1 activates ERK5 by an MEKK2/3-dependent mechanism. The Journal of biological chemistry 123 14681216
2000 MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway. The Journal of biological chemistry 122 11073940
2000 MEKK2 gene disruption causes loss of cytokine production in response to IgE and c-Kit ligand stimulation of ES cell-derived mast cells. The EMBO journal 89 11032806
2021 MAP3K2-regulated intestinal stromal cells define a distinct stem cell niche. Nature 84 33658717
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
2012 MicroRNA-520b inhibits growth of hepatoma cells by targeting MEKK2 and cyclin D1. PloS one 73 22319632
2004 Regulation of c-Jun N-terminal kinase by MEKK-2 and mitogen-activated protein kinase kinase kinases in rheumatoid arthritis. Journal of immunology (Baltimore, Md. : 1950) 73 14734742
2004 MEKK2 regulates the coordinate activation of ERK5 and JNK in response to FGF-2 in fibroblasts. Journal of cellular physiology 72 14978743
2014 EBV microRNA BART 18-5p targets MAP3K2 to facilitate persistence in vivo by inhibiting viral replication in B cells. Proceedings of the National Academy of Sciences of the United States of America 61 25012295
2019 LncRNA FOXD3-AS1 promotes proliferation, invasion and migration of cutaneous malignant melanoma via regulating miR-325/MAP3K2. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 57 31541886
2018 Kir2.1 Interaction with Stk38 Promotes Invasion and Metastasis of Human Gastric Cancer by Enhancing MEKK2-MEK1/2-ERK1/2 Signaling. Cancer research 56 29549164
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
2020 The malectin-like receptor-like kinase LETUM1 modulates NLR protein SUMM2 activation via MEKK2 scaffolding. Nature plants 55 32839517
2015 Stk38 protein kinase preferentially inhibits TLR9-activated inflammatory responses by promoting MEKK2 ubiquitination in macrophages. Nature communications 52 25981615
2014 The oncoprotein HBXIP enhances migration of breast cancer cells through increasing filopodia formation involving MEKK2/ERK1/2/Capn4 signaling. Cancer letters 52 25304384
2011 The kinases MEKK2 and MEKK3 regulate transforming growth factor-β-mediated helper T cell differentiation. Immunity 52 21333552
2002 Disruption of Mekk2 in mice reveals an unexpected role for MEKK2 in modulating T-cell receptor signal transduction. Molecular and cellular biology 52 12138187
2005 Identification of MEKK2/3 serine phosphorylation site targeted by the Toll-like receptor and stress pathways. The EMBO journal 50 16362041
2016 Structure-Based Design of a Novel SMYD3 Inhibitor that Bridges the SAM-and MEKK2-Binding Pockets. Structure (London, England : 1993) 49 27066749
2016 MEKK2 mediates an alternative β-catenin pathway that promotes bone formation. Proceedings of the National Academy of Sciences of the United States of America 47 26884171
1999 Live cell fluorescence imaging of T cell MEKK2: redistribution and activation in response to antigen stimulation of the T cell receptor. Immunity 45 10549623
2005 Dimerization through the catalytic domain is essential for MEKK2 activation. The Journal of biological chemistry 43 15695508
2006 Brain-derived neurotrophic factor activates ERK5 in cortical neurons via a Rap1-MEKK2 signaling cascade. The Journal of biological chemistry 42 17003042
2020 microRNA-93-5p promotes hepatocellular carcinoma progression via a microRNA-93-5p/MAP3K2/c-Jun positive feedback circuit. Oncogene 41 32719439
2016 MicroRNA-186 suppresses cell proliferation and metastasis through targeting MAP3K2 in non-small cell lung cancer. International journal of oncology 41 27498924
2015 The microRNA-520a-3p inhibits proliferation, apoptosis and metastasis by targeting MAP3K2 in non-small cell lung cancer. American journal of cancer research 41 25973317
2010 CHIP-dependent termination of MEKK2 regulates temporal ERK activation required for proper hyperosmotic response. The EMBO journal 41 20588253
2019 Circular RNA circ-PITX1 promotes the progression of glioblastoma by acting as a competing endogenous RNA to regulate miR-379-5p/MAP3K2 axis. European journal of pharmacology 40 31493405
2005 Mip1, an MEKK2-interacting protein, controls MEKK2 dimerization and activation. Molecular and cellular biology 40 15988011
2023 Bestrophin3 Deficiency in Vascular Smooth Muscle Cells Activates MEKK2/3-MAPK Signaling to Trigger Spontaneous Aortic Dissection. Circulation 37 37203562
2008 XIAP regulates bi-phasic NF-kappaB induction involving physical interaction and ubiquitination of MEKK2. Cellular signalling 33 18761086
2020 MIR205HG acts as a ceRNA to expedite cell proliferation and progression in lung squamous cell carcinoma via targeting miR-299-3p/MAP3K2 axis. BMC pulmonary medicine 32 32513149
2014 Restoration of miR17/20a in solid tumor cells enhances the natural killer cell antitumor activity by targeting Mekk2. Cancer immunology research 32 24801835
2018 MEKK2 and MEKK3 suppress Hedgehog pathway-dependent medulloblastoma by inhibiting GLI1 function. Oncogene 31 29662197
2014 Lysine methylation in cancer: SMYD3-MAP3K2 teaches us new lessons in the Ras-ERK pathway. BioEssays : news and reviews in molecular, cellular and developmental biology 31 25382779
2014 Ubiquitin-dependent regulation of MEKK2/3-MEK5-ERK5 signaling module by XIAP and cIAP1. The EMBO journal 27 24975362
2012 MAP kinase kinase kinase-2 (MEKK2) regulates hypertrophic remodeling of the right ventricle in hypoxia-induced pulmonary hypertension. American journal of physiology. Heart and circulatory physiology 25 23125215
2022 E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2. EMBO reports 24 36161689
2022 CircRNA circBACH1 facilitates hepatitis B virus replication and hepatoma development by regulating the miR-200a-3p/MAP3K2 axis. Histology and histopathology 23 35352818
2019 miR-302a inhibits human HepG2 and SMMC-7721 cells proliferation and promotes apoptosis by targeting MAP3K2 and PBX3. Scientific reports 23 30765768
2017 Regulation of cancerous progression and epithelial-mesenchymal transition by miR-34c-3p via modulation of MAP3K2 signaling in triple-negative breast cancer cells. Biochemical and biophysical research communications 23 28069384
2020 CircPUM1 promotes hepatocellular carcinoma progression through the miR-1208/MAP3K2 axis. Journal of cellular and molecular medicine 22 33320435
2014 MEKK2 regulates focal adhesion stability and motility in invasive breast cancer cells. Biochimica et biophysica acta 21 24491810
2006 Protein kinase C alpha, betaI, and betaII isozymes regulate cytokine production in mast cells through MEKK2/ERK5-dependent and -independent pathways. Cellular immunology 21 16430878
2020 LncRNA HCP5 promotes neuroblastoma proliferation by regulating miR-186-5p/MAP3K2 signal axis. Journal of pediatric surgery 20 33189302
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
2021 Circular RNA UBAP2 promotes the proliferation of prostate cancer cells via the miR-1244/MAP3K2 axis. Oncology letters 19 33968202
2010 Calcium regulation of EGF-induced ERK5 activation: role of Lad1-MEKK2 interaction. PloS one 19 20830310
2018 Hippo kinase NDR2 inhibits IL-17 signaling by promoting Smurf1-mediated MEKK2 ubiquitination and degradation. Molecular immunology 18 30504095
2021 Pazopanib ameliorates acute lung injuries via inhibition of MAP3K2 and MAP3K3. Science translational medicine 17 33910977
2020 RNA Interference-Based Screen Reveals Concerted Functions of MEKK2 and CRCK3 in Plant Cell Death Regulation. Plant physiology 17 32165446
2020 MAP3K2 augments Th1 cell differentiation via IL-18 to promote T cell-mediated colitis. Science China. Life sciences 17 32737854
2011 Hepatitis B virus X protein promotes hepatoma cell proliferation via upregulation of MEKK2. Acta pharmacologica Sinica 17 21804577
2023 CircHSPG2 knockdown attenuates hypoxia-induced apoptosis, inflammation, and oxidative stress in human AC16 cardiomyocytes by regulating the miR-1184/MAP3K2 axis. Cell stress & chaperones 16 36810972
2021 MEKK2 and MEKK3 orchestrate multiple signals to regulate Hippo pathway. The Journal of biological chemistry 16 33571521
2021 MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2. EMBO reports 16 34821000
2017 MiR-17-5p and miR-20a promote chicken cell proliferation at least in part by upregulation of c-Myc via MAP3K2 targeting. Scientific reports 16 29158522
2021 Upregulation of miR-335 reduces myocardial injury following myocardial infarction via targeting MAP3K2. European review for medical and pharmacological sciences 15 33506923
2021 miR‑3613‑3p/MAP3K2/p38/caspase‑3 pathway regulates the heat‑stress‑induced apoptosis of endothelial cells. Molecular medicine reports 15 34278472
2021 The Effect and Mechanism of lncRNA NR2F1-As1/miR-493-5p/MAP3K2 Axis in the Progression of Gastric Cancer. Journal of oncology 15 34335755
2016 Sublytic C5b-9 Induces Glomerular Mesangial Cell Apoptosis through the Cascade Pathway of MEKK2-p38 MAPK-IRF-1-TRADD-Caspase 8 in Rat Thy-1 Nephritis. Journal of immunology (Baltimore, Md. : 1950) 15 28039298
2013 MEKK2 kinase association with 14-3-3 protein regulates activation of c-Jun N-terminal kinase. The Journal of biological chemistry 15 23963453
2012 Development and validation of a high-throughput intrinsic ATPase activity assay for the discovery of MEKK2 inhibitors. Journal of biomolecular screening 15 23134735
2023 The SMYD3-MAP3K2 signaling axis promotes tumor aggressiveness and metastasis in prostate cancer. Science advances 14 37976356
2020 MEKK2 mediates aberrant ERK activation in neurofibromatosis type I. Nature communications 14 33177525
2019 Silencing of the MEKK2/MEKK3 Pathway Protects against Spinal Cord Injury via the Hedgehog Pathway and the JNK Pathway. Molecular therapy. Nucleic acids 14 31382189
2015 Identification of ponatinib and other known kinase inhibitors with potent MEKK2 inhibitory activity. Biochemical and biophysical research communications 14 26056008
2022 hsa-miR-340-5p inhibits epithelial-mesenchymal transition in endometriosis by targeting MAP3K2 and inactivating MAPK/ERK signaling. Open medicine (Warsaw, Poland) 13 35415247
2021 MicroRNA-379-5p targets MAP3K2 to reduce autophagy and alleviate neuronal injury following cerebral ischemia via the JNK/c-Jun signaling pathway. The Kaohsiung journal of medical sciences 13 34931755
2019 Prevention of calpain-dependent degradation of STK38 by MEKK2-mediated phosphorylation. Scientific reports 12 31690749
2014 MEKK2 regulates paxillin ubiquitylation and localization in MDA-MB 231 breast cancer cells. The Biochemical journal 12 25190348
2022 MiR-372-3p Functions as a Tumor Suppressor in Colon Cancer by Targeting MAP3K2. Frontiers in genetics 10 35432472
2016 Platelet-derived growth factor (PDGF)-induced activation of Erk5 MAP-kinase is dependent on Mekk2, Mek1/2, PKC and PI3-kinase, and affects BMP signaling. Cellular signalling 10 27339033
2003 Mutations in protein kinase subdomain X differentially affect MEKK2 and MEKK1 activity. Biochemical and biophysical research communications 9 12659851
2013 Overexpression of MEKK2 is associated with colorectal carcinogenesis. Oncology letters 8 24179519
2022 miRNA-338-3p inhibits the migration, invasion and proliferation of human lung adenocarcinoma cells by targeting MAP3K2. Aging 7 35929837
2023 Regulation of a Novel CircTRRAP/miR-761/MAP3K2 CeRNA Cascade in Inflammation, Apoptosis, and Oxidative Stress in Human AC16 Cardiomyocytes under Hypoxia Conditions. International heart journal 6 37258120
2021 Allicin regulates Treg/Th17 balance in mice with collagen-induced arthritis by increasing the expression of MEKK2 protein. Food science & nutrition 6 34026055
2020 MicroRNA-335 inhibits the growth, chemo-sensitivity, and metastasis of human breast cancer cells by targeting MAP3K2. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 6 32521851
2018 Discovery and characterization of an iminocoumarin scaffold as an inhibitor of MEKK2 (MAP3K2). Biochemical and biophysical research communications 6 29309787
2022 MicroRNA152-3p Protects Against Ischemia/Reperfusion-Induced Bbb Destruction Possibly Targeting the MAP3K2/JNK/c-Jun Pathway. Neurochemical research 5 36445489
2019 Inhibitory Effect on the Hepatitis B Cells through the Regulation of miR-122-MAP3K2 signal pathway. Anais da Academia Brasileira de Ciencias 5 31141015
2024 HuR facilitates miR-93-5p-induced activation of MAP3K2 translation via MAP3K2 3'UTR ARE2 in hepatocellular carcinoma. Biochemical and biophysical research communications 4 38795452
2025 LINC01871 facilitates cervical cancer cell migration and immune escape by targeting miR-873-3p/MAP3K2 axis. The Kaohsiung journal of medical sciences 3 40035259
2025 Elevated miR-17-5p facilitates mycobacterial immune evasion by targeting MAP3K2 in macrophages. Frontiers in immunology 3 41425567
2024 MiR-106a-5p by Targeting MAP3K2 Promotes Repair of Oxidative Stress Damage to the Intestinal Barrier in Prelaying Ducks. Animals : an open access journal from MDPI 3 38612276
2021 Submicron silica particles have cytotoxicities on hepatocellular carcinoma, non-small cell lung cancer and breast cancer by unified regulating the XLOC_001659/miR-98-5p/MAP3K2-mediated pathway. Toxicology research 3 34484674
2001 In vitro activity of MEKK2 and MEKK3 in detergents is a function of a valine to serine difference in the catalytic domain. Biochimica et biophysica acta 3 11343802
2025 Transcription factor XBP1s promotes endometritis-induced epithelial-mesenchymal transition by targeting MAP3K2, a key gene in the MAPK/ERK pathway. Cell communication and signaling : CCS 2 39930412
2025 MiR-340-5p alleviates AECOPD by targeting MAP3K2 via Qingjin Huatan decoction therapy. Journal of leukocyte biology 2 39973067
2024 miR-92b-3p Protects against Myocardial Ischemia-Reperfusion Injury by Inhibiting MAP3K2 in a Mouse Model. The Thoracic and cardiovascular surgeon 2 38692270
2022 ZSWIM1 Promotes the Proliferation and Metastasis of Lung Adenocarcinoma Cells through the STK38/MEKK2/ERK1/2 Axis. Journal of proteome research 2 36511424
2022 CircRNA PDE3B regulates tumorigenicity via the miR-136-5p/MAP3K2 axis of esophageal squamous cell carcinoma. Histology and histopathology 2 36533720
2015 Interaction with the Paxillin LD1 Motif Relieves MEKK2 Auto-inhibition. Journal of molecular signaling 2 27096002
2025 The diagnostic value of miR-340-5p in pediatric ulcerative colitis and its molecular mechanism by targeting MAP3K2 to modulate intestinal epithelial cell dysfunction. Hereditas 1 41257990
2025 Structural basis for MEKK2 dimerization and substrate recognition. Nature communications 1 41318559
2021 MicroRNA-335 inhibits the growth, chemo-sensitivity, and metastasis of human breast cancer cells by targeting MAP3K2. Journal of B.U.ON. : official journal of the Balkan Union of Oncology 1 34269003
2024 Fufang Zhenshu Tiaozhi capsule enhances bone formation and safeguards against glucocorticoid-induced osteoporosis through innovative Mekk2-mediated β-catenin deubiquitination. Journal of bone and mineral metabolism 0 38755327

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