Affinage

MAP3K2

Mitogen-activated protein kinase kinase kinase 2 · UniProt Q9Y2U5

Length
619 aa
Mass
69.7 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

MAP3K2 (MEKK2) is a serine/threonine MAP3K that serves as a central signaling hub coupling diverse extracellular stimuli—including growth factors, cytokines, and reactive oxygen species—to downstream MAPK cascades and non-canonical substrates in immune regulation, bone formation, intestinal homeostasis, and vascular integrity. Through its N-terminal PB1 domain, MAP3K2 scaffolds MEK5 for ERK5 pathway activation and, upon its own activation, recruits MKK7 via a distinct PB1 surface to additionally engage JNK signaling; it also phosphorylates MKK4, p38 substrates, and non-MAPK targets including β-catenin (Ser675), p47phox (Ser208), GLI1, LATS1/2, and STK38 (Ser91) (PMID:12912994, PMID:17452462, PMID:26884171, PMID:33910977, PMID:29662197, PMID:33571521, PMID:31690749). MAP3K2 activation is triggered by dimerization through its kinase domain, upstream kinases (WNK1, Rap1), adaptor-mediated recruitment (Lad1, paxillin LD1 motif), and trans-autophosphorylation at Ser519, and is negatively regulated by 14-3-3 binding, SMYD3-mediated K260 methylation that blocks PP2A dephosphorylation, and multiple E3 ubiquitin ligases (Smurf1, XIAP/cIAP1, CHIP, NEDD4L) that target MAP3K2 for ubiquitin-dependent degradation or PB1-domain competition (PMID:15695508, PMID:14681216, PMID:23963453, PMID:24847881, PMID:15820682, PMID:24975362, PMID:20588253, PMID:36161689). Genetic ablation of MAP3K2 reveals stimulus-selective requirements: loss of FcεRI/c-Kit–driven JNK in mast cells, impaired FGF2-induced ERK5/JNK in fibroblasts, augmented T cell proliferation reflecting negative modulation of TCR signaling, and compromised intestinal stem cell maintenance via the ROS–ERK5–KLF2–RSPO1 axis (PMID:11032806, PMID:14978743, PMID:12138187, PMID:33658717).

Mechanistic history

Synthesis pass · year-by-year structured walk · 17 steps
  1. 1999 High

    MAP3K2 was placed at the T cell immunological synapse: imaging showed MEKK2 translocation to the T cell–APC contact, and dominant-negative MEKK2 blocked TCR-mediated ERK and p38 activation, establishing it as a receptor-proximal MAP3K in adaptive immunity.

    Evidence Immunocytochemistry and dominant-negative expression in T cell conjugate assays

    PMID:10549623

    Open questions at the time
    • Upstream signal recruiting MEKK2 to the synapse not identified
    • Kinase-dead versus dominant-negative effects not separated
  2. 2000 High

    A direct link between MAP3K2 and the MEK5–ERK5 cascade was identified, and MEKK2 knockout in mast cells revealed stimulus-selective JNK dependence, demonstrating that MAP3K2 routes specific receptor tyrosine kinase signals to both ERK5 and JNK.

    Evidence Yeast two-hybrid identification of MEK5 as MEKK2 partner; MEKK2−/− ES cell-derived mast cells tested for FcεRI/c-Kit versus UV-induced JNK

    PMID:11032806 PMID:11073940

    Open questions at the time
    • Mechanism of stimulus selectivity unknown
    • Whether ERK5 and JNK are activated simultaneously or sequentially from the same complex unclear
  3. 2002 High

    MEKK2 knockout mice unexpectedly showed enhanced rather than reduced T cell activation, revealing that MAP3K2 negatively modulates TCR signal strength in vivo.

    Evidence Mekk2−/− mice with T cell proliferation, cytokine ELISA, and JNK/ERK/p38 kinase assays

    PMID:12138187

    Open questions at the time
    • Mechanism of negative modulation (direct kinase substrate versus scaffold sequestration) not resolved
    • Redundancy with MEKK3 in T cells not tested
  4. 2003 High

    The structural basis for MAP3K2 scaffolding was established: PB1 domain heterodimerization with MEK5 is required for ERK5 activation, and WNK1 was identified as an upstream kinase that phosphorylates MAP3K2 to relay signals to ERK5.

    Evidence PB1 domain mutagenesis and in vitro binding; WNK1 in vitro kinase assay and dominant-negative epistasis in HEK293 cells

    PMID:12912994 PMID:14681216

    Open questions at the time
    • Phosphorylation site(s) on MEKK2 targeted by WNK1 not mapped
    • Structural basis of PB1–PB1 interaction not yet resolved at atomic level
  5. 2004 High

    MAP3K2 was shown to coordinate both ERK5 and JNK downstream of FGF-2 in fibroblasts and to undergo stimulus-dependent nuclear translocation to relay signals to nuclear MEK5, providing spatial regulation of MAPK signaling.

    Evidence MEKK2−/− MEFs tested for FGF-2/LPS/TNFα-selective pathway loss; immunofluorescence and subcellular fractionation in HeLa/Rat-1 cells after EGF

    PMID:14978743 PMID:15075238

    Open questions at the time
    • Nuclear import mechanism (NLS, carrier) not identified
    • How stimulus selectivity is encoded at the molecular level unresolved
  6. 2005 High

    Multiple layers of MAP3K2 regulation were uncovered: activation requires kinase-domain dimerization; the inhibitor Mip1 blocks dimerization of inactive MEKK2; Smurf1 ubiquitinates MEKK2 for proteasomal degradation controlling osteoblast JNK signaling; and Ser519 was identified as a key activation-loop phosphorylation site induced by TLR/TRAF6.

    Evidence Chemical-induced dimerization system; Mip1 Co-IP and siRNA; Smurf1−/− mice; phospho-S519 mutagenesis with LPS stimulation

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

    Open questions at the time
    • Identity of the kinase that phosphorylates Ser519 (autophosphorylation versus upstream kinase) not fully resolved
    • How TRAF6 activates MEKK2 Ser519 phosphorylation mechanistically unclear
  7. 2007 High

    The bifunctional nature of the MAP3K2 PB1 domain was defined: its front face binds MEK5 constitutively, while its C-terminal acidic cluster recruits MKK7 only upon MEKK2 activation, explaining how one scaffold sequentially activates ERK5 then JNK.

    Evidence PB1 domain face-specific mutagenesis with Co-IP and ERK5/JNK pathway assays

    PMID:17452462

    Open questions at the time
    • Ternary complex stoichiometry not determined
    • Whether MEKK2 simultaneously engages MEK5 and MKK7 or switches between them unknown
  8. 2010 High

    CHIP E3 ligase was identified as a negative regulator that promotes MAP3K2 degradation and limits ERK activation duration under hyperosmotic stress, and calcium was shown to regulate the MEKK2–Lad1 interaction required for EGF-induced ERK5 signaling.

    Evidence CHIP Co-IP and knockout with ERK time-course; calcium-dependent MEKK2–Lad1 Co-IP and in vitro binding

    PMID:20588253 PMID:20830310

    Open questions at the time
    • How calcium modulates MEKK2–Lad1 binding structurally not known
    • CHIP recognition motif on MEKK2 not mapped
  9. 2011 High

    Combined MAP3K2/MAP3K3 deletion in T cells revealed crosstalk with TGF-β signaling: loss of MEKK2/3-mediated SMAD2/3 linker phosphorylation unleashed TGF-β-driven Treg and Th17 accumulation, connecting MAP3K2 to adaptive immune tolerance.

    Evidence Map3k2−/−Map3k3(Lck-Cre/−) mice with Th cell differentiation and phospho-SMAD analysis; EAE model

    PMID:21333552

    Open questions at the time
    • Direct kinase–substrate relationship between MEKK2 and SMAD linker phosphorylation versus intermediate kinases not resolved
    • Relative contributions of MEKK2 and MEKK3 not separated
  10. 2013 High

    14-3-3 binding to phospho-Thr283 on MAP3K2 was shown to suppress trans-autophosphorylation at Ser519, establishing 14-3-3 as a tonic brake on MAP3K2 activation.

    Evidence Phosphorylation site mapping, 14-3-3 binding assay, complementation in MEKK2−/− cells

    PMID:23963453

    Open questions at the time
    • Kinase responsible for Thr283 phosphorylation not identified
    • Stoichiometry of 14-3-3–MEKK2 complex in vivo unknown
  11. 2014 High

    Two new regulatory paradigms for MAP3K2 emerged: SMYD3-mediated K260 methylation blocks PP2A binding to sustain Ras-ERK signaling in cancer, and XIAP/cIAP1-conjugated K63-ubiquitin chains on MEKK2 competitively disrupt MEK5 PB1-domain binding to inactivate ERK5.

    Evidence SMYD3 methylation assays with mouse pancreatic/lung cancer models; XIAP K63-ubiquitin linkage determination and PB1 competition assays with myoblast differentiation readout

    PMID:24847881 PMID:24975362

    Open questions at the time
    • Whether K260 methylation and K63-ubiquitination can co-occur on the same molecule unknown
    • SMYD3-MAP3K2 axis not yet validated in human patient tumors with matched methylation data
  12. 2016 High

    MAP3K2 was established as a direct kinase for non-MAPK substrates: phosphorylation of β-catenin at Ser675 recruits USP15 to stabilize β-catenin and promote bone formation, and the co-crystal structure of the SMYD3–MEKK2 peptide interface was solved.

    Evidence MEKK2−/− mice with in vitro kinase assays and genetic interaction with β-catenin null alleles; co-crystal structure of SMYD3 with MEKK2 substrate peptide

    PMID:26884171 PMID:27066749

    Open questions at the time
    • Whether β-catenin Ser675 phosphorylation by MEKK2 operates in tissues beyond bone not tested
    • Full-length MEKK2 structure unavailable
  13. 2018 High

    Additional non-MAPK substrates were identified: MAP3K2 phosphorylates GLI1 to promote its interaction with SUFU and suppress Hedgehog signaling, and phosphorylates STK38 at Ser91 to protect it from calpain cleavage, expanding MAP3K2's substrate repertoire beyond canonical MAPK intermediates.

    Evidence In vitro kinase assays mapping GLI1 phosphosites with Co-IP for GLI1–SUFU; MEKK2 kinase assay on STK38 with Ser91 mutagenesis and calpain cleavage reconstitution

    PMID:29662197 PMID:31690749

    Open questions at the time
    • Physiological contexts where MEKK2-GLI1 axis operates in vivo not fully defined
    • Whether STK38 Ser91 phosphorylation feeds back to regulate MEKK2 stability via Smurf1 not tested
  14. 2020 High

    Genetic epistasis in mouse bone placed MAP3K2 downstream of NF1 loss in a noncanonical ERK activation pathway: MEKK2 deletion rescued NF1-deficiency skeletal phenotypes, nominating MAP3K2 as a therapeutic target in neurofibromatosis.

    Evidence MEKK2−/− crossed with Nf1fl/fl conditional KO mice; skeletal phenotype analysis with pharmacological MEKK2 inhibitor

    PMID:33177525

    Open questions at the time
    • Direct biochemical mechanism linking NF1 loss to MEKK2 hyperactivation not defined
    • Clinical translation of MEKK2 inhibitors for NF1 skeletal disease not tested
  15. 2021 High

    MAP3K2's physiological roles expanded to intestinal stem cell maintenance (ROS–MEKK2–ERK5–KLF2–RSPO1 in stromal cells), Hippo pathway regulation (direct phosphorylation of LATS1/2 and YAP/TAZ), NADPH oxidase activation (p47phox Ser208 phosphorylation in myeloid cells), and IL-18-driven Th1 differentiation in the gut.

    Evidence MAP3K2−/− mice with intestinal injury and single-cell transcriptomics; in vitro kinase assays for LATS1/2 and YAP/TAZ; myeloid-specific MAP3K2/3 KO and p47phox-S208A knockin in ALI models; T cell transfer colitis with MAP3K2−/− cells

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

    Open questions at the time
    • Whether MEKK2 phosphorylation of LATS1/2 is direct in all cell types or context-dependent not established
    • Relative contribution of MAP3K2 versus MAP3K3 in Hippo and p47phox pathways not fully separated
  16. 2022 High

    NEDD4L was identified as an additional E3 ligase that degrades MAP3K2 via a negative feedback loop triggered by IL-17-induced Ser520 phosphorylation, reinforcing that MAP3K2 protein levels are tightly controlled by multiple ubiquitin ligases in inflammatory signaling.

    Evidence Co-IP, ubiquitination assays, phospho-Ser520 mutagenesis, Nedd4l KO mice with IL-17 stimulation

    PMID:36161689

    Open questions at the time
    • Whether Smurf1 and NEDD4L compete for the same or distinct ubiquitination sites on MEKK2 not resolved
    • Phosphatase that reverses Ser520 phosphorylation not identified
  17. 2023 High

    Bestrophin-3 was shown to directly bind MAP3K2 and suppress its Ser153 phosphorylation, preventing phosphorylation-dependent stabilization; Best3 deficiency hyperactivates MEKK2 and causes aortic dissection, linking MAP3K2 regulation to vascular integrity.

    Evidence Best3 smooth muscle-specific KO mice with Co-IP/MS, single-cell RNA-seq, and MEKK2/3 inhibitor rescue of aortic phenotype

    PMID:37203562

    Open questions at the time
    • Whether Best3 regulation of MEKK2 occurs in tissues beyond vasculature not tested
    • How Ser153 phosphorylation blocks ubiquitin-mediated degradation mechanistically unknown

Open questions

Synthesis pass · forward-looking unresolved questions
  • A full-length structure of MAP3K2 is lacking, the complete phosphorylation code governing activation versus degradation is incompletely mapped, and the basis for stimulus-selective pathway routing through MAP3K2 remains a central unresolved question.
  • No full-length crystal or cryo-EM structure of MAP3K2
  • Complete catalog of direct phosphorylation substrates in different cell types not established
  • How MAP3K2 achieves stimulus selectivity (FGF vs. TNF vs. LPS) at the molecular level is unclear

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 10 GO:0060090 molecular adaptor activity 3
Localization
GO:0005886 plasma membrane 2 GO:0005634 nucleus 1 GO:0005829 cytosol 1
Pathway
R-HSA-162582 Signal Transduction 9 R-HSA-168256 Immune System 6 R-HSA-1266738 Developmental Biology 3 R-HSA-5357801 Programmed Cell Death 1
Partners
CHIPMAP2K5MAP2K7NEDD4LSMURF1SMYD3WNK1XIAP
Complex memberships
MEKK2–MEK5 (PB1-mediated)MEKK2–MKK7 (PB1-mediated)STRIPAK–MEKK3 (related)Smurf1–MEKK2

Evidence

Reading pass · 44 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
2014 SMYD3 methyltransferase methylates MAP3K2 at lysine 260, which potentiates activation of the Ras/Raf/MEK/ERK signaling module. Methylation of MAP3K2 at K260 blocks binding of the PP2A phosphatase complex to MAP3K2, thereby preventing PP2A-mediated negative regulation of MAP kinase signaling. Protein array to identify SMYD3 substrates, in vitro methylation assays, mass spectrometry, Co-IP, mouse cancer models (pancreatic and lung adenocarcinoma), MEK inhibitor synergy studies Nature High 24847881 37976356
2005 Smurf1, a HECT domain ubiquitin E3 ligase, physically interacts with MAP3K2 (MEKK2) and promotes its ubiquitination and proteasomal degradation, thereby suppressing osteoblast activity and JNK signaling downstream of BMP. Co-IP, ubiquitination assays, Smurf1 knockout mice, western blot for phospho-MEKK2 accumulation Cell High 15820682
2003 WNK1 acts upstream of MAP3K2 (MEKK2) and MAP3K3 (MEKK3) in the ERK5 pathway: WNK1 phosphorylates MEKK2 and MEKK3 in vitro, co-immunoprecipitates with endogenous WNK1, and dominant-negative MEKK2/3 block WNK1-induced ERK5 activation. Co-immunoprecipitation, in vitro kinase assay, dominant-negative overexpression, siRNA knockdown, HEK293 cell transfection The Journal of biological chemistry High 14681216
2000 MAP3K2 (MEKK2) directly binds MEK5 (identified by yeast two-hybrid) and activates the MEK5-BMK1/ERK5 pathway; MEKK2 also binds the T cell adapter protein Lad/RIBP and co-localizes with it at the T cell/antigen-presenting cell interface during T cell activation. Yeast two-hybrid library screening, dominant-negative overexpression, live-cell co-localization imaging, kinase activity assays The Journal of biological chemistry High 11073940
2003 The N-terminal PB1 domains of MEKK2 and MEKK3 heterodimerize with the PB1 domain of MEK5 (but not with each other), and this PB1-mediated interaction is required for complex formation and ERK5 pathway activation. Deletion or mutation of the MEKK2 PB1 domain abolishes MEKK2-MEK5 complexes and blocks ERK5 activation. In vitro PB1 domain binding assays, co-immunoprecipitation from cell lysates, deletion/point mutants, dominant-negative overexpression The Journal of biological chemistry High 12912994
2000 MEKK2 gene disruption in ES cell-derived mast cells causes loss of receptor-mediated JNK activation and cytokine gene transcription in response to IgE receptor (FcεRI) or c-Kit ligation, while UV-induced JNK activation remains intact, demonstrating that MEKK2 is specifically required for tyrosine kinase receptor signaling in mast cells. Targeted gene disruption (MEKK2−/− ES cell-derived mast cells), kinase activity assays, cytokine mRNA measurement The EMBO journal High 11032806
2004 MEKK2 coordinates activation of both ERK5 and JNK pathways in response to FGF-2; MEKK2-knockout MEFs lose ERK5 and JNK activation specifically in response to FGF-2 (but not LPS or TNFα), and show impaired AP-1 component expression and cytokine gene induction. MEKK2−/− mouse embryonic fibroblasts, kinase activity assays, RT-PCR for AP-1 components and cytokines Journal of cellular physiology High 14978743
2002 MEKK2 knockout mice exhibit augmented T cell proliferation and enhanced IL-2 and IFNγ production in response to anti-CD3 stimulation, with moderately enhanced (not reduced) JNK activation in MEKK2−/− T cells, indicating MEKK2 negatively modulates TCR signal strength. Mekk2−/− mouse generation, T cell proliferation assays, cytokine ELISA, JNK/ERK/p38 kinase assays Molecular and cellular biology High 12138187
2004 In resting cells MEKK2 is localized in the cytosol, and upon EGF stimulation it translocates into the nucleus where MEK5 and ERK5 are constitutively localized, allowing transmission of signals to nuclear MEK5. Immunofluorescence, in situ NP-40 detergent extraction, subcellular fractionation, EGF stimulation of HeLa and Rat-1 cells Journal of cell science High 15075238
1999 MEKK2 is translocated to the T cell/antigen-presenting cell contact interface upon antigen stimulation of the TCR; dominant-negative MEKK2 inhibits TCR-mediated conjugate stabilization and ERK and p38 MAP kinase phosphorylation. Immunocytochemistry, live-cell fluorescence imaging, dominant-negative expression, kinase phosphorylation assays Immunity High 10549623
2005 MEKK2 activation requires dimerization through its catalytic domain: inactive/non-phosphorylated MEKK2 forms more dimers than phosphorylated MEKK2, and chemical-induced dimerization in vivo augments MEKK2-dependent JNK activation. Prevention of dimerization inhibits JNK signaling. Dimerization domain mapping, chemical-induced dimerization (CID) system, co-immunoprecipitation, JNK/AP-1 reporter assays The Journal of biological chemistry High 15695508
2005 A novel MEKK2-interacting protein, Mip1, forms a complex with inactive/non-phosphorylated MEKK2 and prevents its activation by blocking MEKK2 dimer formation. EGF stimulation dissociates the endogenous Mip1-MEKK2 complex; Mip1 siRNA knockdown augments MEKK2-mediated JNK and AP-1 activation. Co-immunoprecipitation, siRNA knockdown, MEKK2 dimerization assays, JNK/ERK5/AP-1 reporter assays Molecular and cellular biology High 15988011
2005 Serine 519 of MEKK2 (and the corresponding Ser526 of MEKK3) is a key regulatory phosphorylation site: S519A mutation severely impairs MEKK2 activation; LPS (via TRAF6) induces phosphorylation at this serine, which is required for TLR-induced IL-6 production. Site-directed mutagenesis, phospho-specific antibody generation, in vitro kinase assays, LPS stimulation, siRNA knockdown of TRAF6 The EMBO journal High 16362041
2007 The MEKK2 PB1 domain uses a front-to-back arrangement to bind MEK5 in quiescent cells, and upon MEKK2 activation, the C-terminal acidic cluster of the MEKK2 PB1 domain (not required for MEK5 binding) binds and activates MKK7, leading to JNK activation. This defines how one scaffold coordinates sequential ERK5 then JNK signaling. PB1 domain mutagenesis, co-immunoprecipitation, ERK5 and JNK activation assays, ternary complex mapping Molecular and cellular biology High 17452462
2006 BDNF activates ERK5 in cortical neurons via a Rap1-MEKK2-MEK5 cascade: BDNF activates Rap1 and MEKK2; inhibition of either Rap1 or MEKK2 attenuates BDNF-induced ERK5 activation; BDNF stimulation of MEKK2 is Rap1-dependent. Ras and MEKK3 do not play significant roles in neurons. Dominant-negative/constitutively active Rap1 and MEKK2 constructs, kinase activity assays, primary rat cortical neuron cultures The Journal of biological chemistry High 17003042
2008 XIAP interacts with MEKK2 and ubiquitinates it following TNFα stimulation, regulating a second wave of NF-κB activation. Co-immunoprecipitation, ubiquitination assay, NF-κB reporter assay, TNFα stimulation Cellular signalling Medium 18761086
2010 The E3 ubiquitin ligase CHIP binds MEKK2 and promotes its degradation; CHIP depletion prolongs MEKK2-mediated ERK activation in response to hyperosmotic stress. Transient (not sustained) ERK activation via MEKK2 is required for proper aquaporin 1 and 5 gene induction under hyperosmotic conditions. Co-immunoprecipitation, siRNA knockdown, gene targeting of CHIP, ERK activation time-course assays, AQP1/AQP5 gene expression The EMBO journal High 20588253
2011 MEKK2 and MEKK3 negatively regulate TGF-β-mediated Th cell differentiation: Map3k2−/−Map3k3(Lck-Cre/−) mice accumulate Treg and Th17 cells, and their T cells show impaired phosphorylation of SMAD2/3 at linker regions (which negatively regulate TGF-β responses), indicating MAPK-TGF-β pathway crosstalk. Conditional double knockout mice, Th cell differentiation assays, phospho-SMAD western blots, EAE disease model Immunity High 21333552
2013 MEKK2 kinase activity is regulated by phosphorylation-dependent association with 14-3-3 proteins. MEKK2 is phosphorylated at Thr-283, reducing activation-loop phosphorylation at Ser-519 and 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. Phosphorylation site mapping, 14-3-3 binding assays, MEKK2−/− background complementation, JNK/ERK activity assays, IL-6 measurement The Journal of biological chemistry High 23963453
2014 XIAP and cIAP1 directly interact with MEKK2/3 and conjugate predominantly K63-linked ubiquitin chains to MEKK2 and MEKK3, which competitively disrupts MEK5 binding (competing with PB1 domain interaction) and leads to ERK5 pathway inactivation. Loss of XIAP causes hyperactivation of ERK5 and promotes skeletal muscle cell differentiation. Direct Co-IP, ubiquitin linkage determination (K63), competition binding assays, XIAP/cIAP1 knockdown, ERK5 activation assays, myoblast differentiation The EMBO journal High 24975362
2015 Stk38 (NDR kinase) constitutively associates with Smurf1 E3 ligase and facilitates Smurf1-mediated MEKK2 ubiquitination and degradation, specifically suppressing TLR9/CpG-induced ERK1/2 activation and inflammatory cytokine production (TNF-α, IL-6) but not LPS-induced responses. Co-IP, ubiquitination assay, Stk38 KO mice, TLR9 stimulation assays, CpG vs. LPS specificity Nature communications High 25981615
2016 MEKK2 mediates an alternative (non-canonical) β-catenin activation pathway in osteoblasts: FGF2 activates MEKK2, which phosphorylates β-catenin at Ser675, promoting recruitment of the deubiquitinase USP15, which prevents β-catenin ubiquitination and degradation, thereby enhancing WNT signaling and bone formation. MEKK2−/− mice, in vitro kinase assays, phospho-β-catenin mapping, USP15 Co-IP, genetic interaction studies with β-catenin null alleles, MS phosphoproteomics Proceedings of the National Academy of Sciences of the United States of America High 26884171
2016 SMYD3 co-crystal structure with a MEKK2-peptide substrate reveals the substrate-binding tunnel. Structure-based design of GSK2807, a SAM-competitive inhibitor that bridges the SAM-binding pocket and the MEKK2 substrate lysine tunnel of SMYD3 (Ki = 14 nM), blocking MAP3K2 methylation. Co-crystal structure of SMYD3/MEKK2 peptide, kinetic characterization, inhibitor design and structure determination Structure High 27066749
2018 MEKK2 and MEKK3 inhibit GLI1 transcriptional activity and promote GLI1 interaction with SUFU by phosphorylating multiple Ser/Thr sites on GLI1, reducing GLI1 protein stability and DNA-binding ability, thereby suppressing Hedgehog pathway signaling. FGF2-mediated inhibition of Hh signaling requires MEKK2 and MEKK3. In vitro kinase assays, phosphorylation site mapping on GLI1, co-immunoprecipitation (GLI1-SUFU), medulloblastoma cell proliferation assays Oncogene High 29662197
2018 Kir2.1 interacts with Stk38 to inhibit Smurf1-mediated ubiquitination and degradation of MEKK2, thereby stabilizing MEKK2 and activating the MEK1/2-ERK1/2-Snail EMT pathway in gastric cancer cells. This function is independent of K+ ion permeation. Co-immunoprecipitation, ubiquitination assays, siRNA knockdown, Kir2.1 mutants (ion-permeation defective), xenograft metastasis assays Cancer research High 29549164
2021 MAP3K2 mediates a ROS-MAP3K2-ERK5-KLF2 signaling axis in intestinal stromal cells (MRISCs) that drives R-spondin 1 production to maintain LGR5+ intestinal stem cells and protect against acute intestinal damage. MAP3K2−/− mice, intestinal injury models, single-cell transcriptomics, epigenetic profiling, ROS manipulation, RSPO1 measurement Nature High 33658717
2021 MEKK2 and MEKK3 regulate the Hippo pathway: they interact with and phosphorylate LATS1/2 and YAP/TAZ; TNF activates LATS1/2 and inhibits YAP/TAZ through MEKK2/3. STRIPAK complex associates with MEKK3 via CCM2/CCM3 to inactivate MEKK3, and upstream Hippo signals trigger dissociation of MEKK3 from STRIPAK. Co-immunoprecipitation, in vitro kinase assays for LATS1/2 and YAP/TAZ phosphorylation, genetic knockdown, TNF stimulation The Journal of biological chemistry High 33571521
2021 MAP3K2-mediated Th1 cell differentiation in the intestine is regulated by IL-18 and requires specific JNK activation (IL-18-MAP3K2-JNK axis); MAP3K2-deficient naïve CD4+ T cells transferred into mice have a dramatically reduced ability to induce colitis, with fewer IFNγ-producing but more IL-17A-producing cells. T cell transfer colitis model, MAP3K2−/− mice, in vitro Th1/Th17/Treg differentiation assays, JNK activation assays, IL-18 supplementation Science China. Life sciences High 32737854
2021 Pazopanib inhibits MAP3K2- and MAP3K3-mediated phosphorylation of NADPH oxidase 2 subunit p47phox at Ser208, reducing ROS formation in myeloid cells. Myeloid-specific MAP3K2/MAP3K3 genetic inactivation or hematopoietic p47phox-S208A mutation attenuates acute lung injury, establishing MAP3K2 as upstream kinase for p47phox-Ser208 phosphorylation. Genetic inactivation of MAP3K2/3 in myeloid cells, phosphorylation site mutation (p47phox-S208A), ALI mouse models, kinase activity assays Science translational medicine High 33910977
2020 MEKK2 mediates aberrant ERK activation downstream of NF1 (neurofibromin) loss in osteoblasts via a noncanonical ERK pathway. MEKK2-deficient mice crossed with osteoblast-conditional Nf1-knockout mice show amelioration of NF1-associated skeletal phenotypes, placing MEKK2 epistatic to NF1 in ERK activation in bone. MEKK2−/− and Nf1fl/fl conditional KO mice, double-mutant genetic interaction, skeletal phenotype analysis, ERK activation assays, FDA-approved MEKK2 inhibitor in vivo Nature communications High 33177525
2014 MEKK2 ablation in invasive breast cancer cells enhances focal adhesion stability, increases spread area, and reduces cell migration. MEKK2 is activated by and localizes to focal adhesions upon fibronectin/Matrigel attachment, and MEKK2 knockdown inhibits fibronectin-induced ERK5 signaling and FAK autophosphorylation. siRNA knockdown, focal adhesion imaging, cell migration assays, kinase activity assays (MEKK2 activation by attachment), FAK phosphorylation western blot Biochimica et biophysica acta Medium 24491810
2014 MEKK2 physically associates with the LD1 motif of paxillin, induces paxillin ubiquitylation (requiring both the paxillin LD1 motif and MEKK2 kinase activity), and promotes redistribution of paxillin from focal adhesions into the cytoplasm without promoting degradation. Co-immunoprecipitation (MEKK2-paxillin LD1 domain), ubiquitylation assay, MEKK2 kinase-dead mutant, paxillin localization imaging The Biochemical journal Medium 25190348
2015 Paxillin LD1 motif binding to 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 kinase/auto-phosphorylation assay with recombinant paxillin, siRNA paxillin knockdown, LD1 motif binding assay Journal of molecular signaling Medium 27096002
2019 MEKK2 phosphorylates STK38 (Ser91) to protect it from calpain-mediated cleavage at the N-terminal region; MEKK2 knockdown enhances hyperthermia-induced STK38 degradation. A phosphorylation-defective S91A STK38 mutant is susceptible to calpain cleavage. In vitro MEKK2 kinase assay with STK38 substrate, phosphorylation site identification by mass spectrometry, calpain cleavage assay, MEKK2 siRNA knockdown, phospho-defective mutant Scientific reports High 31690749
2022 NEDD4L (HECT E3 ligase) constitutively binds MEKK2 and promotes its poly-ubiquitination and degradation. IL-17-induced MEKK2 Ser520 phosphorylation is required not only for downstream p38 and NF-κB activation but also for NEDD4L-mediated MEKK2 degradation (negative feedback). Nedd4l-deficient mice show increased IL-17-induced inflammation. Co-IP, ubiquitination assay, siRNA knockdown, Nedd4l KO mice, phospho-Ser520 mutagenesis, IL-17 stimulation assays EMBO reports High 36161689
2023 Best3 (Bestrophin3) directly interacts with both MEKK2 and MEKK3 and inhibits phosphorylation of MEKK2 at Ser153 (and MEKK3 at Ser61). Best3 deficiency induces phosphorylation-dependent stabilization of MEKK2/3 (inhibition of ubiquitination/turnover), activating downstream MAPK signaling and triggering aortic dissection. Co-IP coupled with mass spectrometry, Best3 smooth muscle-specific KO mice, single-cell RNA sequencing, proteomics, phosphorylation site analysis, MEKK2/3 inhibitor rescue Circulation High 37203562
2016 SMYD3-mediated methylation of MAP3K2 promotes epithelial-mesenchymal transition-associated behaviors in prostate cancer cells via a positive feedback loop that continuously promotes high SMYD3 levels, and alters vimentin abundance downstream. SMYD3 catalytic mutant, xenograft mouse models, EMT marker analysis, vimentin expression measurement Science advances Medium 37976356
2018 NDR2 (LATS/NDR kinase family) promotes Smurf1-mediated K48-linked ubiquitination of MEKK2 in cells, reducing MEKK2 levels and inhibiting IL-17-induced MAPK and NF-κB activation; Smurf1 knockdown similarly increases IL-17-induced cytokine expression. Co-IP (NDR2-Smurf1), ubiquitination assay with K48-linkage determination, siRNA knockdown, IL-17 stimulation, cytokine quantification Molecular immunology Medium 30504095
2004 In rheumatoid arthritis fibroblast-like synoviocytes (FLS), IL-1 increases MEKK2 kinase activity (measured by immunoprecipitation kinase assay using MKK4 and MKK7 as substrates), and MEKK2 immunoprecipitates activate c-Jun via JNK; activity blocked by JNK inhibitor SP600125. Immunoprecipitation kinase assay with MKK4/MKK7 substrates, c-Jun phosphorylation assay, pharmacological JNK inhibitor Journal of immunology Medium 14734742
2010 Calcium is required for EGF-induced ERK5 activation upstream of MEKK2. EGF increases MEKK2 binding to adaptor protein Lad1 in a calcium-dependent manner; in vitro binding assays show calcium is needed for direct MEKK2-Lad1 interaction. Calcium also regulates EGF-induced nuclear translocation of MEKK2. Co-immunoprecipitation, in vitro direct binding assay, intracellular calcium modifiers, nuclear translocation imaging PloS one Medium 20830310
2003 Point mutations in protein kinase subdomain X (distinct from MEKK1 equivalent residues) impair MEKK2 phosphorylation of MKK7 and MEK5, abolish MEKK2-induced JNK1 and ERK5 activation, and diminish AP-1 reporter gene activation, revealing subdomain X as critical for MEKK2 substrate interaction. Site-directed mutagenesis, in vitro kinase assays with MKK7/MEK5 substrates, JNK1/ERK5 activation assays, AP-1 reporter gene Biochemical and biophysical research communications Medium 12659851
2016 MEKK2 mediates ERK5 activation downstream of PDGF-BB in smooth muscle cells in a manner dependent on Mek1/2, Mek5, PI3-kinase, and classical PKC isoforms, demonstrating co-regulation between ERK1/2 and ERK5 pathways. Dominant-negative MEKK2, kinase activity assays, PI3K/PKC inhibitors, ERK5 activation measurement in MOVAS cells Cellular signalling Medium 27339033
2016 In sublytic C5b-9-induced glomerular mesangial cell apoptosis, MEKK2 phosphorylation (at Ser153/164/239) activates p38 MAPK, which drives IRF-1 and TRADD expression, leading to caspase 8 activation and apoptosis. Silencing MEKK2 in vivo inhibits GMC apoptosis in rat Thy-1 nephritis. Phosphorylation site mutagenesis (Ser153/164/239), p38 MAPK kinase assays, IRF-1/TRADD gene silencing in vivo, caspase 8 activity assay, rat Thy-1 nephritis model Journal of immunology Medium 28039298
2022 ZSWIM1 interacts with STK38 (identified by IP-MS) and antagonizes STK38 function, promoting release and activation of MEKK2, leading to ERK1/2 activation and lung adenocarcinoma progression. Immunoprecipitation-mass spectrometry (interactome), Co-IP validation, ZSWIM1 overexpression/knockdown, ERK1/2 activation assays Journal of proteome research Medium 36511424

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 318 24847881
2005 Ubiquitin ligase Smurf1 controls osteoblast activity and bone homeostasis by targeting MEKK2 for degradation. Cell 310 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 83 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
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
2012 MicroRNA-520b inhibits growth of hepatoma cells by targeting MEKK2 and cyclin D1. PloS one 72 22319632
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 60 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
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
2018 Kir2.1 Interaction with Stk38 Promotes Invasion and Metastasis of Human Gastric Cancer by Enhancing MEKK2-MEK1/2-ERK1/2 Signaling. Cancer research 55 29549164
2020 The malectin-like receptor-like kinase LETUM1 modulates NLR protein SUMM2 activation via MEKK2 scaffolding. Nature plants 53 32839517
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
2015 Stk38 protein kinase preferentially inhibits TLR9-activated inflammatory responses by promoting MEKK2 ubiquitination in macrophages. Nature communications 51 25981615
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
2013 Deletion of a tandem gene family in Arabidopsis: increased MEKK2 abundance triggers autoimmunity when the MEKK1-MKK1/2-MPK4 signaling cascade is disrupted. The Plant cell 45 23695980
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
2006 Brain-derived neurotrophic factor activates ERK5 in cortical neurons via a Rap1-MEKK2 signaling cascade. The Journal of biological chemistry 42 17003042
2005 Dimerization through the catalytic domain is essential for MEKK2 activation. The Journal of biological chemistry 42 15695508
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 39 15988011
2023 Bestrophin3 Deficiency in Vascular Smooth Muscle Cells Activates MEKK2/3-MAPK Signaling to Trigger Spontaneous Aortic Dissection. Circulation 33 37203562
2008 XIAP regulates bi-phasic NF-kappaB induction involving physical interaction and ubiquitination of MEKK2. Cellular signalling 33 18761086
2014 Restoration of miR17/20a in solid tumor cells enhances the natural killer cell antitumor activity by targeting Mekk2. Cancer immunology research 32 24801835
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 31 32513149
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 CircRNA circBACH1 facilitates hepatitis B virus replication and hepatoma development by regulating the miR-200a-3p/MAP3K2 axis. Histology and histopathology 23 35352818
2022 E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2. EMBO reports 23 36161689
2020 MEKK2 inhibits activation of MAP kinases in Arabidopsis. The Plant journal : for cell and molecular biology 23 32267570
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
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
2020 RNA Interference-Based Screen Reveals Concerted Functions of MEKK2 and CRCK3 in Plant Cell Death Regulation. Plant physiology 16 32165446
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 Pazopanib ameliorates acute lung injuries via inhibition of MAP3K2 and MAP3K3. Science translational medicine 15 33910977
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
2021 MicroRNA-181a restricts human γδ T cell differentiation by targeting Map3k2 and Notch2. EMBO reports 15 34821000
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
2021 miR‑3613‑3p/MAP3K2/p38/caspase‑3 pathway regulates the heat‑stress‑induced apoptosis of endothelial cells. Molecular medicine reports 14 34278472
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
2023 The SMYD3-MAP3K2 signaling axis promotes tumor aggressiveness and metastasis in prostate cancer. Science advances 13 37976356
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
2013 Overexpression of MEKK2 is associated with colorectal carcinogenesis. Oncology letters 8 24179519
2003 Mutations in protein kinase subdomain X differentially affect MEKK2 and MEKK1 activity. Biochemical and biophysical research communications 8 12659851
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
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
2025 Elevated miR-17-5p facilitates mycobacterial immune evasion by targeting MAP3K2 in macrophages. Frontiers in immunology 2 41425567
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
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