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MAP2K7

Dual specificity mitogen-activated protein kinase kinase 7 · UniProt O14733

Length
419 aa
Mass
47.5 kDa
Annotated
2026-04-28
100 papers in source corpus 50 papers cited in narrative 49 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAP2K7 (MKK7) is a dual-specificity MAPK kinase that functions as the dedicated threonine-selective activator of JNK/SAPK, integrating proinflammatory cytokine and cellular stress signals into JNK-dependent transcriptional, proliferative, and apoptotic responses. MKK7 preferentially phosphorylates JNK on Thr183 while MKK4/SEK1 phosphorylates Tyr185, and both kinases act synergistically—often within a preformed signalsome scaffolded by Filamin A—to achieve full JNK bisphosphorylation and maximal catalytic activation (PMID:11062067, PMID:11390361, PMID:20156194). Its intrinsically disordered N-terminal domain harbors three cooperative JNK-docking D-sites whose availability is modulated by alternative splicing (regulated by CELF2 and MBNL1), and its catalytic activity is tuned by inhibitory partners (GADD45β blocking the ATP site, c-FLIPL competing with upstream MAP3Ks, TIPRL recruiting PP2Ac) as well as post-translational modifications including SUMO2/3 conjugation (reversed by redox-sensitive SENP3), neddylation (mediated by RanBP2), and Lys296 monomethylation (by EEF1AKMT3) (PMID:25737554, PMID:14743220, PMID:17110930, PMID:29352108, PMID:26364603, PMID:35753528). Physiologically, MKK7 is essential for neuronal axon elongation via a DLK–MKK7–JNK1–MAP1b module, for G2/M cell cycle progression through JNK-dependent CDC2 expression, and for p53-mediated tumor suppression in oncogene-driven lung and mammary cancers (PMID:22090513, PMID:15039780, PMID:21317887).

Mechanistic history

Synthesis pass · year-by-year structured walk · 14 steps
  1. 1997 High

    Identification of MKK7 as a new JNK-specific MAPKK resolved the question of whether a second kinase besides MKK4 could directly activate JNK, establishing that MKK7 is the primary TNFα- and stress-responsive JNK activator distinct from MKK4 and p38 pathways.

    Evidence Molecular cloning, in vitro kinase assays, and overexpression studies in fibroblasts and hematopoietic cells across three independent laboratories

    PMID:9312105 PMID:9362518 PMID:9372971 PMID:9384583 PMID:9414114

    Open questions at the time
    • Relative contribution of MKK7 vs. MKK4 to endogenous JNK activation not resolved
    • Upstream MAP3K inputs to MKK7 not yet defined
  2. 1998 High

    Demonstration that MKK7 is activated by a broad range of stimuli (IL-3, CD40, BCR, Rac/Cdc42, heat, UV) and drives NFAT-dependent IL-2 transcription in T cells established MKK7 as a central integrator of diverse signals converging on JNK.

    Evidence Endogenous kinase assays in hematopoietic cells and dominant-negative MKK7 blocking IL-2 promoter activation

    PMID:9535930 PMID:9575191

    Open questions at the time
    • MAP3Ks linking specific receptors to MKK7 not yet identified
    • Mechanism of MKK7 activation by GTPases not defined
  3. 1999 High

    Discovery of six MKK7 splice isoforms and identification of DLK and MEKK2/3 as direct upstream MAP3Ks answered which kinases phosphorylate MKK7 and revealed that N-terminal extensions in β/γ isoforms confer direct JNK binding and altered basal activity.

    Evidence Cloning of isoforms, direct binding assays, in vitro kinase reconstitution with DLK and MEKK3, subcellular co-localization in neurons

    PMID:10187804 PMID:10347227 PMID:9891090

    Open questions at the time
    • Functional consequences of isoform-specific JNK binding in vivo not tested
    • Phosphorylation sites on MKK7 mediating activation not mapped
  4. 2000 High

    Quantitative phospho-site mapping resolved the long-standing question of how two kinases activate one substrate: MKK7 preferentially phosphorylates Thr183 and MKK4 preferentially phosphorylates Tyr185 of JNK, with synergistic dual phosphorylation required for maximal activity.

    Evidence In vitro reconstitution with site-specific phosphorylation analysis and mass spectrometry across JNK1, JNK2, and JNK3 isoforms

    PMID:10715136 PMID:11062067

    Open questions at the time
    • Whether ordered sequential phosphorylation is obligatory in vivo not settled
    • Structural basis for site selectivity unknown
  5. 2001 High

    Genetic knockouts established that MKK7 is indispensable for cytokine-induced JNK activation and revealed its role in restraining hematopoietic proliferation through cyclin D1 downregulation and p16INK4a upregulation, while confirming ordered Tyr-then-Thr phosphorylation in vivo.

    Evidence Mkk7−/− and Sek1−/− mice and ES cells, conditional T/B cell knockouts, cell cycle analysis, phospho-specific Western blots

    PMID:11390361 PMID:11418587 PMID:11560992

    Open questions at the time
    • How MKK7 selectively controls cyclin D1/p16 independent of MKK4 not mechanistically resolved
    • Embryonic lethality of full KO limits in vivo analysis
  6. 2004 High

    Identification of GADD45β as a direct inhibitor that blocks MKK7's ATP-binding site linked NF-κB-mediated survival signaling to JNK suppression, and MKK7's requirement for G2/M progression via CDC2 expression established it as both a pro-survival and cell-cycle regulatory node.

    Evidence Direct binding assays, in vitro kinase inhibition, peptide disruption restoring TNFα cytotoxicity; Mkk7−/− MEFs with G2/M arrest and epistasis with c-Jun mutants

    PMID:14743220 PMID:15039780

    Open questions at the time
    • Atomic structure of GADD45β–MKK7 complex not yet solved
    • Whether CDC2 regulation is direct or indirect through additional JNK substrates
  7. 2006 High

    Mapping of three cooperative D-docking sites in MKK7's N-terminus and identification of c-FLIPL as a TNFα-dependent inhibitor that blocks MAP3K access explained how MKK7 achieves substrate specificity and how prolonged JNK activation is prevented.

    Evidence Systematic mutagenesis with quantitative binding/kinase assays; Co-IP in c-Flip−/− fibroblasts with prolonged JNK activation phenotype

    PMID:16533805 PMID:17110930

    Open questions at the time
    • Structural basis of D-site cooperativity unknown
    • c-FLIPL binding site on MKK7 not mapped
  8. 2010 High

    Discovery that Filamin A scaffolds an MKK4–MKK7 complex and that RASSF7/N-Ras inhibits MKK7-to-JNK signaling revealed cytoskeletal and Ras-family-level regulation of MKK7 activity beyond simple kinase cascades.

    Evidence Reciprocal Co-IP and Filamin A-deficient cells; RASSF7 knockdown enhancing JNK/apoptosis with RA-domain requirement

    PMID:20156194 PMID:21278800

    Open questions at the time
    • Whether Filamin scaffolding occurs at specific subcellular sites (e.g., actin stress fibers) under physiological stimuli is unclear
    • Stoichiometry of the RASSF7–MKK7 complex not determined
  9. 2011 High

    Tissue-specific knockouts demonstrated MKK7 functions as a tumor suppressor coupling oncogenic stress to p53 stability and as an essential regulator of neuronal axon elongation via JNK-dependent phosphorylation of cytoskeletal substrates (MAP1b, neurofilament-H, doublecortin).

    Evidence Conditional KO in KRas-driven lung tumors, NeuT-driven mammary tumors, and Nestin-Cre brain; epistasis with JNK1/2 and p53; histology and in utero electroporation

    PMID:21317887 PMID:22090513

    Open questions at the time
    • Whether MKK7 tumor-suppressive function extends beyond p53-proficient contexts not tested
    • Relative contributions of JNK1 vs JNK2 to axon elongation downstream of MKK7 unclear
  10. 2012 High

    Identification of TIPRL as a bridging factor between MKK7 and PP2Ac, and localization of MKK7 mRNA to neuronal growth cones for local translation, revealed spatial and phosphatase-mediated regulatory mechanisms controlling MKK7 activity.

    Evidence Co-IP/GST pull-down/confocal in HCC cells with siTIPRL sensitizing to TRAIL; genome-wide screen for neurite-localized mRNAs with live imaging and DLK–MKK7–JNK1 reconstitution

    PMID:22841785 PMID:23226105

    Open questions at the time
    • Cis-elements directing MKK7 mRNA localization not identified
    • TIPRL binding site on MKK7 not mapped
  11. 2015 High

    NMR and crystal structures of MKK7's disordered N-terminal domain and its JNK1-docked complex, together with discovery of neddylation by RanBP2 and CELF2-driven alternative splicing restoring a D-site, provided an atomic and post-translational framework for understanding MKK7 regulation.

    Evidence NMR ensemble and X-ray crystallography of JNK1–D2 complex; in vitro neddylation assay with RanBP2ΔFG; splicing analysis with CELF2 siRNA and c-Jun phosphorylation readout

    PMID:25737554 PMID:26364603 PMID:26443849

    Open questions at the time
    • Full-length MKK7 structure with all three D-sites simultaneously engaged not available
    • Interplay between neddylation and SUMOylation on the same molecule not examined
  12. 2018 High

    Discovery that SENP3-mediated deSUMOylation activates MKK7 under oxidative/LPS conditions and that selective covalent inhibitors target MKK7's active site established redox-regulated SUMOylation as a physiological switch and provided pharmacological tools for pathway dissection.

    Evidence Conditional Senp3 KO mice with SUMOylation/JNK assays; covalent virtual screening validated by X-ray crystallography of inhibitor–MKK7 complex and Mkk7-KO cell selectivity

    PMID:29352108 PMID:30449673

    Open questions at the time
    • SUMOylation sites on MKK7 not mapped to specific residues
    • In vivo efficacy and selectivity of covalent MKK7 inhibitors not tested in disease models
  13. 2020 High

    Comprehensive crystallography of MKK7's catalytic domain identified an N-terminal regulatory helix governing activation and an allosteric pocket, while MBNL1-regulated exon 2 splicing linked MAP2K7Δexon2 to tumor dedifferentiation, expanding the structural and oncological understanding of MKK7.

    Evidence Multiple crystal structures revealing allosteric mechanism and ibrutinib binding; MBNL1 KD with xenograft stemness assays rescued by JNK inhibition

    PMID:32601196 PMID:32783966

    Open questions at the time
    • Whether the allosteric pocket can be exploited therapeutically remains untested in vivo
    • How MBNL1/CELF2 splicing competition is resolved in different tissues not defined
  14. 2022 High

    Identification of EEF1AKMT3-mediated monomethylation at Lys296 as a negative regulator of MKK7 activity that stabilizes TP53 added lysine methylation to the repertoire of post-translational modifications controlling MKK7.

    Evidence Mass spectrometry identification of Lys296 methylation, phospho-antibody array, gain/loss-of-function in gastric cancer cells

    PMID:35753528

    Open questions at the time
    • Whether Lys296 methylation affects MKK7–JNK binding or catalysis directly not determined
    • Enzyme removing this methylation mark not identified

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the full-length structure of MKK7 engaged with JNK through multiple D-sites simultaneously, the interplay among SUMOylation/neddylation/methylation on the same molecule, and whether MKK7's tumor-suppressive function can be therapeutically harnessed beyond the GADD45β-disruption strategy in myeloma.
  • No full-length MKK7–JNK co-structure available
  • Crosstalk among SUMO, NEDD8, and methyl modifications on MKK7 unexplored
  • In vivo therapeutic targeting of MKK7 allosteric pocket not validated

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
Localization
GO:0005634 nucleus 2 GO:0005829 cytosol 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 6 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3 R-HSA-1266738 Developmental Biology 2 R-HSA-1640170 Cell Cycle 2 R-HSA-9612973 Autophagy 1
Partners
CFLARDLKFLNAGADD45BJNK1JNK2SENP3TIPRL
Complex memberships
ASK1-MKK7-JNK (DUSP22-scaffolded)GADD45β-MKK7 inhibitory complexMKK4-FilaminA-MKK7 signalsome

Evidence

Reading pass · 49 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1997 MKK7 was cloned and identified as a novel MAPKK that specifically activates SAPK/JNK but not p38; it directly phosphorylates and activates JNK/SAPK and is activated by TNFα and environmental stresses; it is the mammalian homolog of Drosophila Hemipterous (Hep) and is activated downstream of Rac1 GTPase Molecular cloning, immunochemical studies, in vitro kinase assay, overexpression in fibroblasts, column fractionation The EMBO journal / The Journal of biological chemistry High 9312105 9384583
1997 Human JNKK2 (MKK7) is a highly specific JNK kinase that does not activate p38, distinguishing it from JNKK1/MKK4 Molecular cloning, co-expression kinase assays in mammalian cells Molecular and cellular biology High 9372971
1997 MKK7 (but not SEK1/MKK4) is activated by Fas stimulation and mediates JNK/SAPK activation in the Fas apoptotic pathway; MKK6 (not MKK7) is the major activator of p38 in Fas signaling Immune-complex kinase assay, peptide inhibitor studies in Jurkat and KB cells The Journal of cell biology High 9362518
1997 MKK7 is the specific activator of JNK/SAPK (not p38 or ERK) stimulated by IL-1 in rabbit liver; purified by S Sepharose chromatography and identified by immunoprecipitation with MKK7-specific antisera Biochemical purification, immunoprecipitation, kinase assay FEBS letters High 9414114
1998 MKK7 plays a major role in activating SAPK/JNK in T lymphocytes; a dominant-negative MKK7 mutant abrogates transcriptional activation of the NFAT response element in the IL-2 promoter, placing MKK7 upstream of JNK in the cyclosporin A-sensitive pathway Dominant-negative expression, IL-2 promoter reporter assay The Journal of biological chemistry High 9575191
1998 Human MKK7 is activated by IL-3, CD40 ligation, B-cell antigen receptor, FcR ligation, heat, UV, anisomycin, hyperosmolarity, TNFα, and constitutively active RAS, RAC, or CDC42; it phosphorylates and activates JNK1 but not p38 in co-expression studies Co-expression kinase assays, immune-complex kinase assay with endogenous MKK7 in hematopoietic cells The Journal of biological chemistry High 9535930
1999 The MKK7 gene encodes six isoforms (alpha/beta/gamma × 1/2) by alternative splicing; the N-terminal extension present in MKK7beta/gamma (but not MKK7alpha) binds directly to the substrate JNK, conferring higher basal activity on beta/gamma isoforms while alpha isoforms show higher fold-induction; MKK7 isoforms localize to both cytoplasmic and nuclear compartments Molecular cloning, direct binding assay, comparative kinase assays, immunofluorescence Molecular and cellular biology High 9891090
1999 DLK (dual leucine zipper-bearing kinase) specifically associates with, phosphorylates, and activates MKK7 in vitro and in vivo, but does not phosphorylate MKK4; DLK and MKK7 co-localize in neuronal subcellular compartments distinct from MKK4 In vitro kinase assay, co-immunoprecipitation, subcellular fractionation, immunocytochemistry The Journal of biological chemistry High 10187804
1999 MEKK3 (and MEKK2) directly activates MKK7 in vitro by immunoprecipitate kinase assay, and coexpression of MEKK3 with MKK7 in COS-7 cells enhances MKK7 autophosphorylation and its ability to activate JNK1 In vitro kinase assay with immunoprecipitates, co-expression in COS-7 cells The Journal of biological chemistry High 10347227
1999 JNKK2 (MKK7) fused to JNK1 creates a constitutively active kinase that phosphorylates JNK1 on both Thr183 and Tyr185, stimulates c-Jun transcriptional activity without exogenous stimulus, and localizes predominantly to the nucleus Fusion protein construction, immunoblotting with phospho-specific antibodies, transient transfection reporter assay, immunofluorescence The Journal of biological chemistry High 10506143
2000 MKK4 shows striking preference for phosphorylating Tyr185 of JNK, while MKK7 shows striking preference for Thr183; together they synergistically activate all three JNK/SAPK1 isoforms tested in vitro In vitro kinase assays with phosphorylation-site-specific analysis on JNK1α1, JNK2α2, JNK3α1 The Biochemical journal High 11062067
2000 MKK7 activates JNK3α1 primarily through threonine monophosphorylation (Thr183) and is largely responsible for JNK3α1 activation; MKK4 alone does not increase JNK3α1 Vmax or phosphorylation but is required for bisphosphorylation and maximal activity In vitro kinase assay, mass spectrometry phosphorylation mapping, kinetic analysis (Vmax, kcat, Km) Biochemistry High 10715136
2001 Genetic disruption of Mkk7 alone is sufficient to prevent JNK activation by proinflammatory cytokines in mouse cells, whereas simultaneous disruption of both Mkk4 and Mkk7 is required to block stress-induced JNK activation; MKK4 preferentially phosphorylates Tyr and MKK7 preferentially phosphorylates Thr on JNK Targeted gene disruption in mice, in vitro phosphorylation assays, MEF cell studies Genes & development High 11390361
2001 MKK7 negatively regulates growth factor and antigen receptor-induced proliferation in hematopoietic cells (T cells, B cells, mast cells); loss of MKK7 completely abolishes SAPK/JNK activation even when MKK4 is upregulated; MKK7-regulated pathway reduces cyclin D1 and increases p16INK4a Conditional gene targeting in mice, proliferation assays, JNK kinase assays, cell cycle analysis The Journal of experimental medicine High 11560992
2001 PKCδ specifically mediates ionizing radiation-induced JNK activation through MKK7 (not MKK4) in human thyroid cells; dominant-negative PKCδ and the PKCδ inhibitor rottlerin suppress IR-induced MKK7 activation and downstream JNK/AP-1 activation Dominant-negative adenoviral vectors, immune-complex kinase assay for MKK4 and MKK7, pharmacological inhibition Oncogene High 11314034
2001 In SEK1-deficient ES cells, stress-induced JNK activation is markedly impaired with loss of Tyr phosphorylation; MKK7alpha1 cannot phosphorylate JNK Thr unless Tyr is first phosphorylated by SEK1, while MKK7gamma2 can phosphorylate both residues; sequential phosphorylation by SEK1 (Tyr) then MKK7 (Thr) is required for synergistic JNK activation mkk7−/− and sek1−/− ES cell generation, co-transfection phosphorylation analysis, kinase-dead mutants, HEK293T assays The Journal of biological chemistry High 11418587
2002 ZAK MAP3K activates JNK/SAPK specifically via MKK7 and not MKK4; dominant-negative MKK7 but not MKK4 attenuates ZAK-induced JNK activation Dominant-negative co-expression, JNK activation assay Biochemical and biophysical research communications Medium 12220515
2002 SKRP1 (a dual-specificity phosphatase) interacts with MKK7 and through this interaction inactivates JNK; SKRP1 does not bind JNK directly but co-precipitates with MKK7 in vitro and in vivo without disrupting MKK7-JNK interaction Co-immunoprecipitation, GST pull-down, in vitro binding, JNK kinase assay, immunofluorescence co-localization The Journal of biological chemistry High 11959861
2003 MKK4 and MKK7 form a stable complex with JNK in fibroblast-like synoviocytes (FLS); MKK4 co-precipitates with MKK7 and vice versa; the signalsome containing MKK4, MKK7, and JNK co-localizes in the cytoplasm and can phosphorylate c-Jun after IL-1 stimulation Co-immunoprecipitation, confocal microscopy, in vitro kinase assay Arthritis and rheumatism High 13130464
2003 In ES cells lacking MKK7, Thr phosphorylation of JNK is lost without marked reduction in Tyr phosphorylation; SEK1 binds to JNK1 but MKK7 does not; SEK1-induced Tyr phosphorylation precedes and facilitates additional Thr phosphorylation by MKK7 mkk7−/− ES cells, dual phosphorylation analysis with phospho-specific antibodies, co-immunoprecipitation in 293T cells, Thr-Pro-Phe JNK mutant The Journal of biological chemistry High 12624093
2004 GADD45β binds directly to MKK7 and blocks its catalytic activity, thereby linking NF-κB-mediated suppression to inhibition of JNK signaling; peptides disrupting the GADD45β/MKK7 interaction restore TNFα-induced cytotoxicity Co-immunoprecipitation, direct binding assay, in vitro kinase assay, peptide disruption experiments Nature cell biology High 14743220
2004 MKK7 is required for G2/M cell cycle progression and its loss leads to premature senescence and G2/M arrest in MEFs; MKK7-JNK-c-Jun pathway regulates CDC2 expression; loss of c-Jun or expression of c-JunAA (JNK phosphorylation sites mutated) phenocopies MKK7 loss Genetic inactivation of MKK7 in mice, MEF cell cycle analysis, epistasis with c-Jun mutants, CDC2 expression analysis Nature cell biology High 15039780
2006 MKK7 contains three JNK-docking (D) sites in its N-terminal domain that cooperatively mediate JNK binding; mutation of any single D-site reduces binding by 50–70%, mutation of two reduces by 80–90%, and mutation of all three reduces binding by 95%; full-length MKK7 with D1/D2 mutations shows reduced JNK activation Binding assays, mutagenesis, peptide competition assays, JNK kinase activity assays The Journal of biological chemistry High 16533805
2006 c-FLIPL directly interacts with MKK7 in a TNFα-dependent manner and inhibits the interactions of MKK7 with MEKK1, ASK1, and TAK1, thereby selectively suppressing prolonged JNK activation; c-Flip−/− fibroblasts show prolonged JNK activation after TNFα Co-immunoprecipitation, c-Flip−/− fibroblasts, JNK activation assays The EMBO journal High 17110930
2006 In FLS, IL-1β/TNFα-induced JNK activation and MMP-3 production depend specifically on MKK7 but not MKK4; anisomycin-induced JNK requires both MKK4 and MKK7; AP-1 binding activity and AP-1-driven gene expression are strictly MKK7-dependent after cytokine stimulation siRNA knockdown, in vitro JNK kinase assay, AP-1 EMSA, MMP-3 ELISA Arthritis and rheumatism High 16802349
2007 GADD45β is a structured protein with predicted four-stranded β-sheet core and five α-helices; its helices α3/α4 and loops 1/2 mediate MKK7 binding; loop 1 and α4-loop 2 engage the MKK7 ATP-binding site causing conformational changes that impede catalytic function Structural/biophysical analysis of GADD45β, mutagenesis mapping of MKK7 interaction surfaces, in vitro kinase inhibition assay The Journal of biological chemistry High 17485467
2008 GADD45β forms non-covalent homodimers in solution via predicted helices 1 and 5; it forms a large complex with MKK7 (at minimum a tetrameric MKK7-GADD45β:GADD45β-MKK7 unit); dimerization surface of GADD45β is distinct from its MKK7-binding surface Biophysical (CD, SEC, NMR-based), mutagenesis of dimerization interface Journal of molecular biology High 18343408
2009 Oncogenic H-Ras activates a Rac1→MKK7→JNK signaling cascade that upregulates Atg5 to induce autophagic cell death; MKK7 (not MKK4) specifically mediates H-RasV12-induced JNK activation; inhibition of MKK7 by siRNA suppresses Atg5 upregulation and autophagic death siRNA knockdown of MKK7/MKK4, siRNA for Rac1, JNK activation assays, autophagy readouts Carcinogenesis High 19783847
2010 Filamin A (and B, C) binds to MKK7 (via its N-terminal region present in MKK7γ and MKK7β but not MKK7α) and to MKK4 through different binding regions, enabling formation of an MKK4-Filamin A-MKK7 complex; Filamin A-deficient cells show impaired MKK7 activation and reduced synergistic JNK activation Co-immunoprecipitation, co-localization with actin stress fibers, Filamin A-deficient cells, deletion mutagenesis The Biochemical journal High 20156194
2010 RASSF7 interacts with MKK7 and, together with N-Ras, promotes the phosphorylated state of MKK7 while inhibiting MKK7's ability to activate JNK; RASSF7 depletion enhances JNK activation and apoptosis; RASSF7 requires its RA domain for interaction with GTP-bound N-Ras and the anti-apoptotic response Co-immunoprecipitation, RNAi knockdown, JNK activation assay, apoptosis assay Cell death and differentiation High 21278800
2011 Tissue-specific inactivation of MKK7 in KRas(G12D)-driven lung and NeuT-driven mammary tumors accelerates tumor onset; mechanistically MKK7 acts through JNK1 and JNK2 to couple oncogenic/genotoxic stress to p53 stability required for cell cycle arrest Conditional tissue-specific KO in cancer mouse models, epistasis with JNK1/JNK2, p53 stability assays Nature genetics High 21317887
2011 MKK7 deletion in the nervous system (Nestin-Cre conditional KO) causes severe brain developmental defects including enlarged ventricles, reduced striatum, minimal axon tracts, and impaired axon elongation; phosphorylation of JNK substrates c-Jun, neurofilament heavy chain, MAP1B, and doublecortin is reduced; MKK7 regulates axon elongation in a cell-autonomous manner Conditional KO, histology, immunofluorescence, in utero electroporation, in vitro neuronal assays, electron microscopy The Journal of neuroscience High 22090513
2011 Cardiomyocyte-specific deletion of MKK7 leads to heart failure under pressure overload, with increased cardiomyocyte apoptosis, elevated p53, attenuated MnSOD expression, and extensive interstitial fibrosis with upregulated TGF-β signaling Cardiomyocyte-specific KO mice, pressure overload model, apoptosis/fibrosis assays, Western blotting Journal of molecular and cellular cardiology High 21284947
2012 TIPRL binds to MKK7 and PP2Ac, promotes their interaction, and thereby prevents prolonged MKK7 phosphorylation/JNK activation; siTIPRL combined with TRAIL causes sustained MKK7/JNK activation and apoptosis in HCC cells; confirmed by Co-IP, confocal microscopy, and GST pull-down Co-immunoprecipitation, GST pull-down, confocal microscopy, siRNA knockdown, JNK phosphorylation assay Gastroenterology High 22841785
2012 MKK7 mRNA is localized to the growth cone where it can be translated; MKK7 is then phosphorylated in the neurite shaft as part of a DLK-MKK7-JNK1 module; this triggers MAP1b phosphorylation to regulate microtubule bundling leading to neurite elongation Genome-wide screen for neurite-enriched mRNAs, live cell imaging, phosphorylation assays, neurite elongation assays PLoS biology High 23226105
2013 Active Rac1 negatively regulates Schwann cell differentiation through the MKK7-JNK pathway (not Raf-ERK); MKK7 activation and c-jun induction in sciatic nerves after axotomy is blocked by Rac inhibition; ErbB2/neuregulin signaling activates MKK7 to drive Schwann cell dedifferentiation Primary Schwann cell culture, dominant-active/negative constructs, Rac inhibition, MKK7 activation assay, microarray Glia High 23505039
2014 GADD45β/MKK7 interaction is a therapeutic target in multiple myeloma; DTP3, a D-tripeptide, disrupts the GADD45β/MKK7 complex, restores MKK7 activity and JNK-mediated apoptosis, kills MM cells selectively, and ablates myeloma xenografts in mice without apparent toxicity Drug-target interaction assay, Co-IP disruption, kinase activity assay, cell viability assays, xenograft mouse model Cancer cell High 25314077
2014 MAVS recruits MKK7 to mitochondria via its 3D domain; MKK7 then phosphorylates JNK2 (but not JNK1) to activate the apoptosis pathway during viral (Sendai virus) infection; Mkk7−/− cells fail to initiate virus-induced apoptosis Co-immunoprecipitation, Mkk7−/− and Jnk2−/− cells, mitochondrial fractionation, apoptosis assays, viral challenge in vivo PLoS pathogens High 24651600
2015 NMR spectroscopy reveals the MKK7 regulatory N-terminal domain is intrinsically disordered with three JNK-docking sites of varying conformational propensities; crystal structure of JNK1 in complex with MKK7's second docking site reveals two different binding modes of the docking motif NMR spectroscopy, X-ray crystallography of JNK1-MKK7 D-site complex Proceedings of the National Academy of Sciences High 25737554
2015 During T-cell activation, JNK signaling induces CELF2 expression, which promotes skipping of MKK7 exon 2; the exon 2-skipped isoform restores a JNK-docking site disrupted in the full-length isoform, enhancing MKK7-JNK activity (c-Jun phosphorylation, TNF-α upregulation), creating a positive feedback loop Alternative splicing analysis, siRNA, JNK activation assays, c-Jun phosphorylation, RNA-binding assay for CELF2 Genes & development High 26443849
2015 The Ca2+/ASK1/MKK7/JNK2/c-Src cascade mediates DSS-induced intestinal epithelial tight junction disruption; knockdown of MKK7 or ASK1 blocks DSS-induced tight junction disruption and barrier dysfunction; recombinant JNK2 induces threonine phosphorylation and auto-phosphorylation of c-Src siRNA knockdown, Ca2+ depletion, in vitro kinase assay with recombinant JNK2, barrier function assay, animal model The Biochemical journal High 25377781
2016 DUSP22 acts as a scaffold protein for the ASK1-MKK7-JNK signaling complex; DUSP22 selectively associates with ASK1, MKK7, and JNK1/2 but not ERK or p38; it enhances JNK phosphorylation and apoptosis independently of its phosphatase activity, displaying biphasic scaffold behavior Co-immunoprecipitation, mutagenesis of DUSP22 phosphatase activity, JNK activation assay, apoptosis assay PloS one Medium 27711255
2018 SENP3-mediated deSUMOylation of MKK7 promotes MKK7 binding to JNK and enhances JNK phosphorylation; MKK7 undergoes SUMO2/3 modification and SENP3 is a redox-sensitive (ROS-dependent) protease that accumulates after LPS, linking redox signaling to MKK7 activity in macrophages Conditional Senp3 KO mice, Co-immunoprecipitation, SUMOylation assay, JNK phosphorylation assay, LPS in vivo model The Journal of biological chemistry High 29352108
2018 Covalent virtual screening identified selective MKK7 covalent inhibitors; the crystal structure of a lead compound bound to MKK7 confirmed the predicted covalent binding mode; compounds selectively inhibit JNK phosphorylation in cells and block LPS-induced B cell activation Covalent virtual screening, X-ray crystallography of MKK7-inhibitor complex, kinase panel selectivity, KO cell validation, B cell activation assay Cell chemical biology High 30449673
2014 5Z-7-Oxozeaenol covalently binds to MKK7 at Cys218 (located at the end of the hinge region), not at the gatekeeper-2 cysteine; crystal structure of MAP2K7/5Z7O complex confirms this unprecedented binding mode X-ray crystallography of MAP2K7/5Z7O complex Bioorganic & medicinal chemistry letters High 25529738
2020 Crystal structures of MKK7 catalytic domain reveal an N-terminal regulatory helix mediating kinase activation (allosteric mechanism conserved in all MAP2Ks); structures show typical active kinase features when this helix is present; an unprecedented allosteric pocket in the N-terminal lobe binds ibrutinib; type II irreversible inhibitors bind in a mode not previously reported for MKK7 Multiple X-ray crystal structures of MKK7, small-molecule screening, functional kinase assays Cell chemical biology High 32783966
2015 Neddylation of MKK7 (mediated by RanBP2 acting as SUMO/neddylation E3 ligase for MKK7) limits its basal kinase activity; RanBP2 knockdown augments basal JNK phosphorylation; in vitro neddylation of purified MKK7 by RanBP2ΔFG reduces its basal kinase activity In vitro neddylation assay, Co-immunoprecipitation, siRNA knockdown, JNK phosphorylation assay Oncogene High 26364603
2020 MBNL1 suppresses a MAP2K7Δexon2 splice variant; this variant drives JNK activation and tumor dedifferentiation/stem-like properties in MBNL1-low cancers; JNK inhibition reverses MAP2K7Δexon2-driven dedifferentiation MBNL1 knockdown/overexpression, alternative splicing analysis, JNK activation assays, tumor xenograft and in vitro stemness assays Proceedings of the National Academy of Sciences High 32601196
2022 EEF1AKMT3 catalyzes monomethylation of MKK7 at Lys296, which decreases MKK7 phosphorylation, ubiquitination, and degradation of TP53; EEF1AKMT3 knockdown induces gastric tumor invasiveness by activating MAP2K7/MKK7 and downstream JNK signaling Mass spectrometry analysis of MKK7 methylation site, phospho-antibody array, gain/loss-of-function studies, RNA-seq Cancer letters High 35753528

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2001 MKK7 is an essential component of the JNK signal transduction pathway activated by proinflammatory cytokines. Genes & development 307 11390361
2004 Gadd45 beta mediates the NF-kappa B suppression of JNK signalling by targeting MKK7/JNKK2. Nature cell biology 291 14743220
1997 A novel SAPK/JNK kinase, MKK7, stimulated by TNFalpha and cellular stresses. The EMBO journal 232 9384583
1998 T lymphocyte activation signals for interleukin-2 production involve activation of MKK6-p38 and MKK7-SAPK/JNK signaling pathways sensitive to cyclosporin A. The Journal of biological chemistry 177 9575191
2000 Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7. The Biochemical journal 164 11062067
1997 MKK7 is a stress-activated mitogen-activated protein kinase kinase functionally related to hemipterous. The Journal of biological chemistry 155 9312105
1999 The MKK7 gene encodes a group of c-Jun NH2-terminal kinase kinases. Molecular and cellular biology 152 9891090
2006 Physiological roles of MKK4 and MKK7: insights from animal models. Biochimica et biophysica acta 145 17157936
2001 Induction of inducible nitric oxide synthase-NO* by lipoarabinomannan of Mycobacterium tuberculosis is mediated by MEK1-ERK, MKK7-JNK, and NF-kappaB signaling pathways. Infection and immunity 140 11254551
1997 Fas induces cytoplasmic apoptotic responses and activation of the MKK7-JNK/SAPK and MKK6-p38 pathways independent of CPP32-like proteases. The Journal of cell biology 136 9362518
2004 MKK7 couples stress signalling to G2/M cell-cycle progression and cellular senescence. Nature cell biology 127 15039780
2009 The Rac1/MKK7/JNK pathway signals upregulation of Atg5 and subsequent autophagic cell death in response to oncogenic Ras. Carcinogenesis 117 19783847
2021 Anti-inflammatory Effects of Empagliflozin and Gemigliptin on LPS-Stimulated Macrophage via the IKK/NF-κB, MKK7/JNK, and JAK2/STAT1 Signalling Pathways. Journal of immunology research 116 34124273
2011 The bottleneck of JNK signaling: molecular and functional characteristics of MKK4 and MKK7. European journal of cell biology 111 21333379
2016 Mitogen-Activated Protein Kinase Cascade MKK7-MPK6 Plays Important Roles in Plant Development and Regulates Shoot Branching by Phosphorylating PIN1 in Arabidopsis. PLoS biology 104 27618482
1999 The JNKK2-JNK1 fusion protein acts as a constitutively active c-Jun kinase that stimulates c-Jun transcription activity. The Journal of biological chemistry 100 10506143
2007 Activation of c-Jun N-terminal kinase (JNK) by widely used specific p38 MAPK inhibitors SB202190 and SB203580: a MLK-3-MKK7-dependent mechanism. Cellular signalling 99 18222647
2014 Cancer-selective targeting of the NF-κB survival pathway with GADD45β/MKK7 inhibitors. Cancer cell 95 25314077
1997 Molecular cloning and characterization of human JNKK2, a novel Jun NH2-terminal kinase-specific kinase. Molecular and cellular biology 94 9372971
2015 Calcium/Ask1/MKK7/JNK2/c-Src signalling cascade mediates disruption of intestinal epithelial tight junctions by dextran sulfate sodium. The Biochemical journal 88 25377781
1999 The mixed lineage kinase DLK utilizes MKK7 and not MKK4 as substrate. The Journal of biological chemistry 88 10187804
2011 The stress kinase MKK7 couples oncogenic stress to p53 stability and tumor suppression. Nature genetics 85 21317887
2008 Transcriptional regulation of EGR-1 by the interleukin-1-JNK-MKK7-c-Jun pathway. The Journal of biological chemistry 83 18281687
1999 MEK kinase 3 directly activates MKK6 and MKK7, specific activators of the p38 and c-Jun NH2-terminal kinases. The Journal of biological chemistry 83 10347227
1998 Multiple signaling pathways for the activation of JNK in mast cells: involvement of Bruton's tyrosine kinase, protein kinase C, and JNK kinases, SEK1 and MKK7. Journal of immunology (Baltimore, Md. : 1950) 80 9712046
1998 Human mitogen-activated protein kinase kinase 7 (MKK7) is a highly conserved c-Jun N-terminal kinase/stress-activated protein kinase (JNK/SAPK) activated by environmental stresses and physiological stimuli. The Journal of biological chemistry 79 9535930
2005 Suppression of metastatic colonization by the context-dependent activation of the c-Jun NH2-terminal kinase kinases JNKK1/MKK4 and MKK7. Cancer research 72 16322247
2006 An antiapoptotic protein, c-FLIPL, directly binds to MKK7 and inhibits the JNK pathway. The EMBO journal 68 17110930
2002 Possible involvement of IkappaB kinase 2 and MKK7 in osteoclastogenesis induced by receptor activator of nuclear factor kappaB ligand. Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research 67 11918218
2000 Activation of JNK3 alpha 1 requires both MKK4 and MKK7: kinetic characterization of in vitro phosphorylated JNK3 alpha 1. Biochemistry 66 10715136
2003 Different properties of SEK1 and MKK7 in dual phosphorylation of stress-induced activated protein kinase SAPK/JNK in embryonic stem cells. The Journal of biological chemistry 64 12624093
2006 Interacting JNK-docking sites in MKK7 promote binding and activation of JNK mitogen-activated protein kinases. The Journal of biological chemistry 63 16533805
2007 Insights into the structural basis of the GADD45beta-mediated inactivation of the JNK kinase, MKK7/JNKK2. The Journal of biological chemistry 62 17485467
2015 Widespread JNK-dependent alternative splicing induces a positive feedback loop through CELF2-mediated regulation of MKK7 during T-cell activation. Genes & development 60 26443849
2015 Structure and dynamics of the MKK7-JNK signaling complex. Proceedings of the National Academy of Sciences of the United States of America 59 25737554
2001 Impaired synergistic activation of stress-activated protein kinase SAPK/JNK in mouse embryonic stem cells lacking SEK1/MKK4: different contribution of SEK2/MKK7 isoforms to the synergistic activation. The Journal of biological chemistry 59 11418587
2011 Stress-activated protein kinase MKK7 regulates axon elongation in the developing cerebral cortex. The Journal of neuroscience : the official journal of the Society for Neuroscience 57 22090513
2010 The NF (Nuclear factor)-κB inhibitor parthenolide interacts with histone deacetylase inhibitors to induce MKK7/JNK1-dependent apoptosis in human acute myeloid leukaemia cells. British journal of haematology 57 20701602
1998 Differential activation of stress-activated protein kinase kinases SKK4/MKK7 and SKK1/MKK4 by the mixed-lineage kinase-2 and mitogen-activated protein kinase kinase (MKK) kinase-1. The Biochemical journal 55 9639556
2012 TGF-β-associated miR-27a inhibits dendritic cell-mediated differentiation of Th1 and Th17 cells by TAB3, p38 MAPK, MAP2K4 and MAP2K7. Genes and immunity 54 23034448
2003 Expression of the MAPK kinases MKK-4 and MKK-7 in rheumatoid arthritis and their role as key regulators of JNK. Arthritis and rheumatism 54 13130464
2005 The neuroprotective effects of K252a through inhibiting MLK3/MKK7/JNK3 signaling pathway on ischemic brain injury in rat hippocampal CA1 region. Neuroscience 53 15680699
2001 The stress kinase mitogen-activated protein kinase kinase (MKK)7 is a negative regulator of antigen receptor and growth factor receptor-induced proliferation in hematopoietic cells. The Journal of experimental medicine 53 11560992
1999 Differential regulation of mitogen-activated protein kinase kinase 4 (MKK4) and 7 (MKK7) by signaling from G protein beta gamma subunit in human embryonal kidney 293 cells. The Journal of biological chemistry 53 9890951
2018 Covalent Docking Identifies a Potent and Selective MKK7 Inhibitor. Cell chemical biology 52 30449673
2001 PKC delta mediates ionizing radiation-induced activation of c-Jun NH(2)-terminal kinase through MKK7 in human thyroid cells. Oncogene 52 11314034
2009 A non-redundant role for Drosophila Mkk4 and hemipterous/Mkk7 in TAK1-mediated activation of JNK. PloS one 51 19888449
2007 Up-regulation of MKK4, MKK6 and MKK7 during prostate cancer progression: an important role for SAPK signalling in prostatic neoplasia. The Journal of pathology 51 17577251
2012 Inhibition of MKK7-JNK by the TOR signaling pathway regulator-like protein contributes to resistance of HCC cells to TRAIL-induced apoptosis. Gastroenterology 49 22841785
1998 Differential activation of two JNK activators, MKK7 and SEK1, by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2. The Journal of biological chemistry 45 9516438
2008 Elucidation of the signaling network of COX-2 induction in sheared chondrocytes: COX-2 is induced via a Rac/MEKK1/MKK7/JNK2/c-Jun-C/EBPbeta-dependent pathway. American journal of physiology. Cell physiology 44 18367585
2018 DeSUMOylation of MKK7 kinase by the SUMO2/3 protease SENP3 potentiates lipopolysaccharide-induced inflammatory signaling in macrophages. The Journal of biological chemistry 43 29352108
2014 MAVS-MKK7-JNK2 defines a novel apoptotic signaling pathway during viral infection. PLoS pathogens 43 24651600
2012 Converging evidence that sequence variations in the novel candidate gene MAP2K7 (MKK7) are functionally associated with schizophrenia. Human molecular genetics 43 22899651
2012 Growth cone MKK7 mRNA targeting regulates MAP1b-dependent microtubule bundling to control neurite elongation. PLoS biology 43 23226105
2008 Gadd45 beta forms a homodimeric complex that binds tightly to MKK7. Journal of molecular biology 43 18343408
2013 The Neuregulin-Rac-MKK7 pathway regulates antagonistic c-jun/Krox20 expression in Schwann cell dedifferentiation. Glia 42 23505039
2014 MKK7 mediates miR-493-dependent suppression of liver metastasis of colon cancer cells. Cancer science 41 24533778
2006 Regulation of JNK by MKK-7 in fibroblast-like synoviocytes. Arthritis and rheumatism 41 16802349
2002 A novel dual specificity phosphatase SKRP1 interacts with the MAPK kinase MKK7 and inactivates the JNK MAPK pathway. Implication for the precise regulation of the particular MAPK pathway. The Journal of biological chemistry 39 11959861
2019 MKK7, the essential regulator of JNK signaling involved in cancer cell survival: a newly emerging anticancer therapeutic target. Therapeutic advances in medical oncology 38 31579105
2019 Phosphatidic acid promotes the activation and plasma membrane localization of MKK7 and MKK9 in response to salt stress. Plant science : an international journal of experimental plant biology 37 31481213
2016 miR-125b inhibited epithelial-mesenchymal transition of triple-negative breast cancer by targeting MAP2K7. OncoTargets and therapy 37 27226726
2016 Inactivation of KLF4 promotes T-cell acute lymphoblastic leukemia and activates the MAP2K7 pathway. Leukemia 36 27872496
2002 Mixed lineage kinase ZAK utilizing MKK7 and not MKK4 to activate the c-Jun N-terminal kinase and playing a role in the cell arrest. Biochemical and biophysical research communications 36 12220515
2020 A tumor-associated splice-isoform of MAP2K7 drives dedifferentiation in MBNL1-low cancers via JNK activation. Proceedings of the National Academy of Sciences of the United States of America 35 32601196
2019 Histone deacetylase 6 promotes growth of glioblastoma through the MKK7/JNK/c-Jun signaling pathway. Journal of neurochemistry 35 31390677
2011 Alpinetin suppresses proliferation of human hepatoma cells by the activation of MKK7 and elevates sensitization to cis-diammined dichloridoplatium. Oncology reports 35 22159816
1997 Selective activation of JNK/SAPK by interleukin-1 in rabbit liver is mediated by MKK7. FEBS letters 35 9414114
2012 HBx activates FasL and mediates HepG2 cell apoptosis through MLK3-MKK7-JNKs signal module. World journal of gastroenterology 34 22509080
2010 Diverse physiological functions of MKK4 and MKK7 during early embryogenesis. Journal of biochemistry 34 20801953
2010 RASSF7 negatively regulates pro-apoptotic JNK signaling by inhibiting the activity of phosphorylated-MKK7. Cell death and differentiation 34 21278800
2016 Scaffold Role of DUSP22 in ASK1-MKK7-JNK Signaling Pathway. PloS one 33 27711255
2015 Exploring the role of MKK7 in excitotoxicity and cerebral ischemia: a novel pharmacological strategy against brain injury. Cell death & disease 30 26270349
2017 Role of p-MKK7 in myricetin-induced protection against intestinal ischemia/reperfusion injury. Pharmacological research 29 29154988
2011 Deprivation of MKK7 in cardiomyocytes provokes heart failure in mice when exposed to pressure overload. Journal of molecular and cellular cardiology 29 21284947
2006 D-MEKK1, the Drosophila orthologue of mammalian MEKK4/MTK1, and Hemipterous/D-MKK7 mediate the activation of D-JNK by cadmium and arsenite in Schneider cells. BMC cell biology 29 16451733
2022 The EEF1AKMT3/MAP2K7/TP53 axis suppresses tumor invasiveness and metastasis in gastric cancer. Cancer letters 27 35753528
2010 Filamin associates with stress signalling kinases MKK7 and MKK4 and regulates JNK activation. The Biochemical journal 27 20156194
2001 Expression of human cystatin A by keratinocytes is positively regulated via the Ras/MEKK1/MKK7/JNK signal transduction pathway but negatively regulated via the Ras/Raf-1/MEK1/ERK pathway. The Journal of biological chemistry 26 11451947
2021 The bacterial effector HopZ1a acetylates MKK7 to suppress plant immunity. The New phytologist 25 33960430
2018 Mkk4 and Mkk7 are important for retinal development and axonal injury-induced retinal ganglion cell death. Cell death & disease 25 30367030
2006 A change of expression in the conserved signaling gene MKK7 is associated with a selective sweep in the western house mouse Mus musculus domesticus. Journal of evolutionary biology 25 16910979
2017 Cordycepin promotes apoptosis in renal carcinoma cells by activating the MKK7-JNK signaling pathway through inhibition of c-FLIPL expression. PloS one 24 29045468
2016 HDAC inhibitors suppress c-Jun/Fra-1-mediated proliferation through transcriptionally downregulating MKK7 and Raf1 in neuroblastoma cells. Oncotarget 24 26734995
2020 Catalytic Domain Plasticity of MKK7 Reveals Structural Mechanisms of Allosteric Activation and Diverse Targeting Opportunities. Cell chemical biology 23 32783966
2015 Identification and characterization of MKK7 as an upstream activator of JNK in Litopenaeus vannamei. Fish & shellfish immunology 23 26707780
2014 5Z-7-Oxozeaenol covalently binds to MAP2K7 at Cys218 in an unprecedented manner. Bioorganic & medicinal chemistry letters 23 25529738
2013 Isoangustone A, a novel licorice compound, inhibits cell proliferation by targeting PI3K, MKK4, and MKK7 in human melanoma. Cancer prevention research (Philadelphia, Pa.) 23 24104352
2015 Neddylation controls basal MKK7 kinase activity in breast cancer cells. Oncogene 22 26364603
2014 Tussilago farfara L. augments TRAIL-induced apoptosis through MKK7/JNK activation by inhibition of MKK7‑TIPRL in human hepatocellular carcinoma cells. Oncology reports 22 24969837
2019 MKK7 transcription positively or negatively regulated by SP1 and KLF5 depends on HDAC4 activity in glioma. International journal of cancer 20 30963560
2018 Probing the interaction interface of the GADD45β/MKK7 and MKK7/DTP3 complexes by chemical cross-linking mass spectrometry. International journal of biological macromolecules 20 29572137
2011 Distinct signaling properties of mitogen-activated protein kinase kinases 4 (MKK4) and 7 (MKK7) in embryonic stem cell (ESC) differentiation. The Journal of biological chemistry 20 22130668
2008 GADD45B inhibits MKK7-induced cardiac hypertrophy and the polymorphisms of GADD45B is associated with inter-ventricular septum hypertrophy. Biochemical and biophysical research communications 20 18515079
2006 Differential requirement of MKK4 and MKK7 in JNK activation by distinct scaffold proteins. FEBS letters 20 17187786
2022 Circular RNA ACTA1 Acts as a Sponge for miR-199a-5p and miR-433 to Regulate Bovine Myoblast Development through the MAP3K11/MAP2K7/JNK Pathway. Journal of agricultural and food chemistry 19 35234473
2019 Targeting the MKK7-JNK (Mitogen-Activated Protein Kinase Kinase 7-c-Jun N-Terminal Kinase) Pathway with Covalent Inhibitors. Journal of medicinal chemistry 19 30768270
2016 Heme Oxygenase-1 Inhibits Neuronal Apoptosis in Spinal Cord Injury through Down-Regulation of Cdc42-MLK3-MKK7-JNK3 Axis. Journal of neurotrauma 19 27526795
2000 Stress-activated protein kinase-dependent induction of c-fos by Cd(2+) is mediated by MKK7. Biochemical and biophysical research communications 19 10873670