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Showing MAP4K4 — NIK is a alias.

MAP4K4

Mitogen-activated protein kinase kinase kinase kinase 4 · UniProt O95819

Length
1239 aa
Mass
142.1 kDa
Annotated
2026-06-10
100 papers in source corpus 36 papers cited in narrative 36 extracted findings
Cross-family judge vs UniProt: tie faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAP4K4 is a Ste20-family serine/threonine kinase that functions as a stress- and inflammation-responsive signaling hub coupling extracellular cues to JNK-pathway activation, cytoskeletal remodeling, and metabolic control (PMID:9890973, PMID:19407801). Classically, MAP4K4 acts upstream of a TAK1→MKK4/MKK7→JNK cascade and is itself activated by TNF-α through TNFR1, with TNF-α also transcriptionally inducing Map4k4 via c-Jun and ATF2 to create a feed-forward inflammatory loop (PMID:9890973, PMID:17500068). In cell migration, MAP4K4 directly phosphorylates moesin at sites of focal adhesion disassembly, where moesin competes with talin to inactivate β1-integrin and promote membrane retraction; MAP4K4 is delivered to focal adhesions along EB2-bound microtubules to activate Arf6 through IQSEC1, driving integrin internalization and adhesion turnover (PMID:25799996, PMID:25490267, PMID:37369604). Beyond moesin, MAP4K4 directly phosphorylates a defined set of substrates to control distinct outputs: TRAF2 (promoting its lysosomal degradation to limit IL-6) (PMID:25098764), MLK3 at Thr738 (PMID:34511598), ADAM10 at Ser436 (stabilizing N-cadherin) (PMID:36922678), VASP at Ser157 (PMID:35941177), FARP1 (PMID:26422651), and Drp1 (facilitating its S-nitrosylation at Cys644 via GPX4 suppression to drive endothelial ferroptosis) (PMID:38724987). Metabolically, MAP4K4 suppresses adipogenesis and lipogenesis by inhibiting mTOR/mTORC1—reducing PPARγ protein translation and, via AMPK-mediated raptor phosphorylation, suppressing SREBP-1—and mediates TNF-α-induced insulin resistance (PMID:16461467, PMID:20038583, PMID:23924694, PMID:25918248). MAP4K4 activity is restrained by STRIPAK: striatins (STRN1/3/4) tether PP2A to keep MAP4K4 dephosphorylated and inactive, linking it to Hippo/YAP and growth control (PMID:31913126, PMID:35941177). Functionally, MAP4K4 promotes neuronal degeneration acting redundantly with MINK1 and TNIK upstream of DLK-driven retrograde JNK stress signaling (PMID:28993483, PMID:30699345), drives oxidative-stress cardiomyocyte death and ischemia-reperfusion injury (PMID:30853557), and restrains CD8 T-cell LFA-1 activation through ERM proteins (PMID:32220977).

Mechanistic history

Synthesis pass · year-by-year structured walk · 21 steps
  1. 1999 High

    Established MAP4K4's core signaling identity by placing it as a JNK-selective upstream kinase responsive to TNF-α, defining the pathway architecture all later work builds on.

    Evidence Dominant-negative epistasis with TAK1/MKK4/MKK7 and TNF-α stimulation in 293T cells

    PMID:9890973

    Open questions at the time
    • Did not identify direct physiological substrates
    • Mechanism of TNF-α-induced MAP4K4 activation left unresolved
  2. 2006 High

    Linked MAP4K4 to physiological outputs—cancer cell migration via JNK and metabolic regulation of adipogenesis/glucose transport—revealing it as more than a stress kinase.

    Evidence Genome-scale siRNA wound-healing screen across carcinoma lines, and RNAi kinase screen in adipocytes with glucose transport readouts

    PMID:16461467 PMID:16537454

    Open questions at the time
    • Migration mechanism downstream of JNK undefined
    • Direct adipocyte substrates not identified
  3. 2007 High

    Defined a feed-forward inflammatory circuit and the insulin-resistance mechanism: TNFR1 induces Map4k4 transcription via c-Jun/ATF2, and MAP4K4 mediates TNF-α-driven IRS-1 serine phosphorylation.

    Evidence Receptor-specific antibodies/siRNA, c-Jun/ATF2 depletion, and epistasis with MAP2K1/MAP2K4 in primary human muscle

    PMID:17227768 PMID:17500068

    Open questions at the time
    • Whether MAP4K4 directly phosphorylates IRS-1 not established
    • In vivo relevance to systemic insulin resistance not yet tested
  4. 2009 High

    Resolved the mechanism of metabolic suppression: MAP4K4 inhibits mTOR signaling to reduce PPARγ translation and acts in macrophages to drive cytokine production, with systemic protective effects.

    Evidence Metabolic labeling/cycloheximide chase with mTOR-4E-BP1 analysis in adipocytes, and in vivo macrophage siRNA in an LPS lethality model

    PMID:19407801 PMID:20038583

    Open questions at the time
    • How MAP4K4 inhibits mTOR mechanistically not fully defined
    • Direct kinase substrate in the mTOR axis unknown
  5. 2012 High

    Showed MAP4K4 kinase activity inhibits myogenesis via Myf5, expanding its developmental roles beyond canonical MAPK cascades.

    Evidence Bidirectional gain/loss-of-function and kinase-dead mutant with Myf5 rescue in C2C12 cells

    PMID:23207904

    Open questions at the time
    • Direct substrate linking MAP4K4 to Myf5 unidentified
    • ERK/p38/JNK-independent mechanism not molecularly defined
  6. 2013 Medium

    Connected MAP4K4 to adhesion-receptor signaling through Pyk2 interaction and demonstrated roles in viral (KSHV) reactivation and invasion.

    Evidence Yeast two-hybrid/Co-IP with Pyk2 FERM domain plus migration epistasis, and siRNA/small-molecule screening in KSHV-infected endothelial cells

    PMID:24163766 PMID:24244164

    Open questions at the time
    • Pyk2-MAP4K4 phosphorylation directionality and sites incompletely mapped
    • KSHV regulation is single-lab, mechanism upstream of COX-2/MMPs unclear
  7. 2013 High

    Dissected the mTORC1/AMPK arm of metabolic control, showing MAP4K4 suppresses lipogenesis via AMPK-raptor-Ser792 and SREBP-1 independently of JNK.

    Evidence Isotope incorporation assays, genetic perturbation, and rapamycin/JNK-depletion controls in adipocytes

    PMID:23924694

    Open questions at the time
    • Whether MAP4K4 directly phosphorylates AMPK not shown
    • Tissue-level lipogenic relevance not yet tested in vivo
  8. 2014 High

    Defined the direct cytoskeletal mechanism of migration: MAP4K4 phosphorylates moesin to inactivate β1-integrin and is trafficked to focal adhesions via EB2 microtubules to activate Arf6 through IQSEC1.

    Evidence Substrate phosphorylation, genetic epistasis, integrin blockade, inducible KO mice, and FA-complex proteomics with Arf6 activation assays

    PMID:25490267 PMID:25799996

    Open questions at the time
    • How MAP4K4 selects moesin among ERM proteins at adhesions unclear
    • Coordination of microtubule delivery with kinase activation not resolved
  9. 2014 High

    Identified TRAF2 as a direct degradative substrate linking MAP4K4 to immune cytokine control, with in vivo consequences for adipose inflammation and insulin resistance.

    Evidence Direct phosphorylation assay and T-cell-specific conditional KO with multiple cytokine/genetic epistasis readouts

    PMID:25098764

    Open questions at the time
    • TRAF2 phosphosite(s) and lysosomal targeting mechanism not fully mapped
  10. 2015 High

    Broadened the direct substrate catalog (FARP1) and provided structural/chemical tools, while clarifying tissue-specific metabolic genetics in vivo.

    Evidence Phosphoproteomics/in vitro kinase profiling for FARP1, X-ray crystallography of inhibitor-bound MAP4K4, and tissue-specific conditional KO metabolic phenotyping

    PMID:25908259 PMID:25918248 PMID:26422651

    Open questions at the time
    • FARP1 phosphosite physiological role undefined
    • Why Myf5-tissue deletion improves adipose insulin sensitivity unexplained
  11. 2015 High

    Extended MAP4K4 to vascular inflammation through NF-κB regulation in endothelium, with atheroprotection upon inhibition.

    Evidence Endothelial-specific gene ablation and small-molecule inhibition in Apoe-/- and Ldlr-/- mice with NF-κB readouts

    PMID:26688060

    Open questions at the time
    • Direct MAP4K4 substrate in the NF-κB pathway not identified
  12. 2016 Medium

    Implicated MAP4K4 in hepatocellular carcinoma proliferation and survival through broad JNK/NF-κB/TLR pathway engagement.

    Evidence shRNA knockdown with PCR-array pathway profiling, cell cycle/apoptosis assays, and xenografts

    PMID:21196414

    Open questions at the time
    • Signaling assignment broad and correlative
    • No direct substrate identified, single-lab
  13. 2017 High

    Established neuronal degeneration roles: MAP4K4 acts redundantly with MINK1/TNIK upstream of DLK-driven retrograde JNK stress signaling.

    Evidence Combinatorial siRNA/pharmacological inhibition in DRG neurons with DLK phosphorylation and retrograde-transport readouts

    PMID:28993483

    Open questions at the time
    • Whether MAP4K4 directly phosphorylates DLK not established
    • Relative contribution of each MAP4K family member in vivo unresolved
  14. 2017 Medium

    Revealed regulatory complexity: alternative splicing of exon 16 (SRSF3/RBM4) tunes JNK1 signaling and EMT, and MAP4K4 can positively regulate ERK by inhibiting PP2A in lung cancer.

    Evidence Splice-variant constructs with JNK1/EMT readouts, and knockdown with PP2A activity/ERK phosphorylation assays plus xenografts

    PMID:28306189 PMID:29138007

    Open questions at the time
    • Functional difference between splice isoforms mechanistically incomplete
    • How MAP4K4 inhibits PP2A unclear, both single-lab
  15. 2018 Medium

    Linked MAP4K4-JNK1-c-Jun signaling to SESN2-dependent autophagy as an antitumor mechanism, and showed MAP4K4 controls c-Met recycling/integrin β1 in medulloblastoma invasion.

    Evidence ChIP of c-Jun at the SESN2 promoter with autophagy assays in osteosarcoma, and endocytosis/recycling measurements in medulloblastoma

    PMID:29796184 PMID:30258193

    Open questions at the time
    • Pharmacological MAP4K4 activation specificity not fully controlled
    • Direct substrate controlling c-Met endocytosis unidentified
  16. 2019 High

    Demonstrated MAP4K4 as a driver of oxidative-stress cardiomyocyte death and motor-neuron degeneration, nominating it as a therapeutic target in heart and ALS contexts.

    Evidence Genetic/pharmacological inhibition (DMX-5804) in hiPSC-CMs and mouse ischemia-reperfusion; knockdown/inhibition in ESC/iPSC/primary motor neurons with JNK3/c-Jun and autophagy readouts

    PMID:30699345 PMID:30853557

    Open questions at the time
    • Direct substrate mediating cardiomyocyte death not identified
    • Link between MAP4K4 and FoxO1-mediated autophagy mechanistically incomplete
  17. 2020 High

    Defined STRIPAK-PP2A as the inhibitory regulator that keeps MAP4K4 dephosphorylated, and showed MAP4K4 negatively regulates CD8 T-cell LFA-1 activation via ERM proteins.

    Evidence ST-PP2A proteomics with STRN4 knockdown/dephosphorylation/YAP1 assays, and genetic/pharmacological MAP4K4 perturbation with LFA-1 epistasis in tumor/viral models

    PMID:31913126 PMID:32220977

    Open questions at the time
    • Which MAP4K4 substrate(s) gate Hippo/YAP downstream of STRIPAK not fully defined
  18. 2021 High

    Expanded the direct substrate repertoire (MLK3-Thr738) in pancreatic cancer and mapped CNH-domain-dependent STRN3 binding coupling MAP4K4 to PP2A and VASP-S157 phosphorylation.

    Evidence Co-IP, site-specific phosphorylation assays, CNH-deletion constructs, and in vivo KPC model

    PMID:34032269 PMID:34511598

    Open questions at the time
    • How STRN3 binding switches between inhibition and substrate selection unresolved
    • Context-dependent MAP4K4 inhibition of JNK in cardiomyocytes (single-lab) not generalized
  19. 2022 Medium

    Clarified STRN3-PP2A control of MAP4K4 growth-repressing activity and VASP-driven invasion, and positioned RhoA-Set-PP2A as an upstream restraint relevant to aortic aneurysm.

    Evidence Co-IP/CNH-domain mapping with VASP-S157 and Hippo assays, and VSMC-specific RhoA cKO with Set-PP2A analysis and DMX-5804

    PMID:35941177 PMID:36207400

    Open questions at the time
    • Set-PP2A-MAP4K4 axis is proposed with limited reconstitution
    • RhoA-to-MAP4K4 link is single-lab
  20. 2023 Medium

    Added ADAM10-Ser436 as a direct substrate stabilizing N-cadherin in ovarian cancer, and resolved that MAP4K4 disassembles adherens junctions by a moesin-independent route in collective migration.

    Evidence Site-specific ADAM10 phosphorylation/cleavage assays with in vivo metastasis, and traction-force microscopy with moesin phosphorylation in A431 cells

    PMID:36922678 PMID:37369604

    Open questions at the time
    • Moesin-independent adherens-junction mechanism not molecularly defined
    • ADAM10 finding single-lab
  21. 2024 High

    Identified Drp1-Cys644 S-nitrosylation (via GPX4 suppression) as a MAP4K4-driven ferroptotic mechanism in diabetic cardiac microvasculature, and PEPT1-dipeptide activation of MAP4K4-G3BP2-Thr227 in HCC metastasis.

    Evidence Site-specific Cys-to-Ala mutation with GPX4/ferroptosis assays and DMX-5804 in db/db mice; PEPT1 perturbation with G3BP2-Thr227 phosphorylation and lung metastasis model

    PMID:38639383 PMID:38724987

    Open questions at the time
    • How MAP4K4 suppresses GPX4 expression mechanistically unclear
    • G3BP2-Thr227 phosphorylation is single-lab

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved how a single kinase integrates its many context-specific substrates and opposite outputs (e.g., JNK activation vs inhibition; growth promotion vs repression), and what governs substrate selection downstream of STRIPAK-PP2A regulation.
  • No unifying structural/regulatory model for substrate selection
  • Context-dependent reversal of JNK output unexplained
  • Endogenous activating signal that overrides STRIPAK inhibition undefined

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016740 transferase activity 4 GO:0140110 transcription regulator activity 2
Localization
GO:0005856 cytoskeleton 3 GO:0005829 cytosol 2 GO:0005815 microtubule organizing center 1
Pathway
R-HSA-1430728 Metabolism 4 R-HSA-1500931 Cell-Cell communication 3 R-HSA-162582 Signal Transduction 3 R-HSA-168256 Immune System 3 R-HSA-5357801 Programmed Cell Death 3
Partners
EB2IQSEC1MLK3PYK2STRN1STRN3STRN4TRAF2
Complex memberships
STRIPAK

Evidence

Reading pass · 36 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1999 MAP4K4 (HGK) is a serine/threonine kinase that specifically activates the JNK signaling pathway but not ERK or p38. HGK-induced JNK activation is inhibited by dominant-negative MKK4 and MKK7 mutants, and dominant-negative TAK1 (but not MEKK1 or MUK) strongly inhibits HGK-induced JNK activation, positioning HGK upstream of TAK1→MKK4/MKK7→JNK. TNF-α activates HGK in 293T cells and dominant-negative HGK mutants inhibit TNF-α-induced JNK activation. Transient transfection of 293T cells with wild-type and dominant-negative kinase constructs, kinase pathway specificity assays, epistasis with dominant-negative pathway components The Journal of biological chemistry High 9890973
2006 MAP4K4 knockdown by siRNA inhibits migration and invasion of multiple carcinoma cell lines, and this pro-migratory effect is mediated through JNK signaling independently of AP-1 transcriptional activation. siRNA knockdown screen (10,996 siRNAs / 5,234 genes), 384-well wound-healing assay, validation in multiple cell lines, small-molecule JNK inhibition Proceedings of the National Academy of Sciences of the United States of America High 16537454
2006 MAP4K4/NIK is a negative regulator of PPARγ expression, adipogenesis, and insulin-stimulated glucose transport in adipocytes. MAP4K4 suppresses expression of C/EBPα, C/EBPβ, PPARγ, and GLUT4. TNF-α-induced GLUT4 downregulation requires MAP4K4 expression. RNAi screen of protein kinases in adipocytes, siRNA knockdown, gene expression analysis, glucose transport assays Proceedings of the National Academy of Sciences of the United States of America High 16461467
2007 MAP4K4 mediates TNF-α-induced insulin resistance in human skeletal muscle by promoting JNK and ERK-1/2 phosphorylation and IRS-1 serine phosphorylation. Silencing MAP4K4 prevents TNF-α-induced inhibition of glucose uptake and rescues Akt and AS160 signaling. Silencing downstream MAP2K1 and MAP2K4 recapitulates MAP4K4 siRNA effects, placing MAP4K4 upstream of these kinases. siRNA knockdown in primary human skeletal muscle cells, glucose uptake assays, phosphorylation analysis by western blot, epistasis with MAP2K1/MAP2K4 siRNA The Journal of biological chemistry High 17227768
2007 TNF-α selectively upregulates Map4k4 mRNA expression through TNFR1 (not TNFR2), and this requires the transcription factors c-Jun and ATF2. siRNA depletion of c-Jun and ATF2 attenuates TNF-α-induced Map4k4 expression. Agonistic/antagonistic antibodies and siRNA against TNFR1/TNFR2, siRNA depletion of c-Jun and ATF2, mRNA quantification in cultured adipocytes The Journal of biological chemistry High 17500068
2009 Map4k4 negatively regulates PPARγ at the post-transcriptional level by inhibiting mTOR signaling (reducing 4E-BP1 phosphorylation), thereby decreasing PPARγ protein translation rather than altering mRNA levels or PPARγ degradation. Map4k4 depletion requires mTOR and 4E-BP1 to increase PPARγ protein levels. siRNA knockdown, [35S]methionine/cysteine labeling to measure protein synthesis, cycloheximide chase for degradation measurement, adenovirus-mediated MAP4K4 overexpression, mTOR/4E-BP1 pathway analysis The Journal of biological chemistry High 20038583
2009 Map4k4 in macrophages is a mediator of cytokine (TNF-α and IL-1β) expression. Silencing Map4k4 in macrophages in vivo protected mice from LPS-induced lethality by inhibiting TNF-α and IL-1β production. GeRP-mediated siRNA delivery to macrophages in vivo, LPS-induced lethality model, cytokine measurement Nature High 19407801
2012 Map4k4 is a negative regulator of skeletal muscle differentiation. Its kinase activity is essential for this inhibitory function, as a kinase-inactive mutant enhances myotube formation. Map4k4 acts through upregulation of the myogenic factor Myf5: Map4k4 silencing upregulates Myf5, and Myf5 is required for the enhanced myogenesis seen with Map4k4 depletion. This mechanism is independent of ERK, p38, or JNK signaling. siRNA knockdown and adenovirus-mediated overexpression in C2C12 cells, kinase-inactive mutant expression, Myf5 rescue experiments, myogenic gene expression and myotube morphology analysis Molecular and cellular biology High 23207904
2013 Map4k4 suppresses adipocyte lipogenesis by inhibiting mTORC1 via AMPK-mediated phosphorylation of raptor (Ser792), leading to suppression of Srebp-1 protein expression and cleavage. This mechanism is independent of JNK signaling: Map4k4 silencing enhances lipogenesis and Srebp-1 upregulation without affecting JNK, and Map4k4 overexpression fails to activate endogenous JNK. siRNA knockdown, full-genome microarray, 14C-glucose and 14C-acetate incorporation into TGs/fatty acids, Srebp-1 rescue experiments, rapamycin treatment, JNK depletion comparison Journal of lipid research High 23924694
2014 MAP4K4 phosphorylates moesin in retracting membranes of migrating endothelial cells at sites of focal adhesion disassembly. Moesin functions downstream of MAP4K4 to inactivate β1-integrin by competing with talin for binding to the β1-integrin intracellular domain, thereby promoting membrane retraction and focal adhesion disassembly. Epistasis analyses established moesin downstream of MAP4K4; α5β1-integrin blockade reversed membrane retraction defects caused by MAP4K4 loss. siRNA and chemical inhibitor screens, phosphorylation analysis, epistasis analysis, α5β1-integrin blocking, in vitro and in vivo angiogenesis assays, inducible Map4k4 knockout mice Nature High 25799996
2014 MAP4K4 associates with microtubule plus-end binding protein EB2 and the Arf6 GEF IQSEC1. MAP4K4 is delivered to focal adhesions via EB2-bound microtubules, where it activates Arf6 through IQSEC1, promoting integrin internalization and focal adhesion disassembly. MAP4K4 knockout stabilizes focal adhesions and impairs cell migration. Quantitative proteomics (MAP4K4 FA-associated complex), knockout, co-immunoprecipitation, Arf6 activation assay, microtubule association studies Developmental cell High 25490267
2014 HGK/MAP4K4 directly phosphorylates TRAF2, promoting its lysosomal degradation and thereby inhibiting IL-6 production in T cells. In T-cell-specific MAP4K4 knockout mice, TRAF2 is stabilized, IL-6 is overproduced, and this drives Th17 differentiation in adipose tissue leading to insulin resistance. T-cell-specific conditional knockout mice, direct phosphorylation assay, IL-6 and IL-17 neutralization, CCL20 neutralization, CCR6 knockout epistasis, leptin receptor knockout epistasis Nature communications High 25098764
2015 MAP4K4 directly phosphorylates and coimmunoprecipitates with FARP1 (FERM, RhoGEF, and pleckstrin domain-containing protein 1). MAP4K4 favors a pTL motif in vitro based on kinase specificity profiling. MAP4K4 inhibition in SH-SY5Y cells increases neurite outgrowth, a process known to involve FARP1. Phosphoproteomic analysis of MAP4K4 inhibition, in vitro kinase specificity assay, co-immunoprecipitation, direct phosphorylation assay, neurite outgrowth assay ACS chemical biology High 26422651
2015 MAP4K4 is identified as the protein target of militarinone-inspired 4-hydroxy-2-pyridone neuritogenic compounds. The most potent compound is a selective ATP-competitive inhibitor of MAP4K4, confirmed by biochemical analysis and a crystal structure of the inhibitor in complex with MAP4K4. Target identification via activity-based profiling, biochemical kinase assays, X-ray crystallography of inhibitor-MAP4K4 complex Angewandte Chemie (International ed. in English) High 25908259
2015 MAP4K4 promotes vascular inflammation and atherosclerosis in endothelial cells by activating NF-κB (reducing its nuclear localization and activity when MAP4K4 is silenced), leading to decreased cell surface adhesion molecule expression and reduced macrophage recruitment. Endothelial-specific MAP4K4 siRNA and gene ablation in Apoe−/− mice, small-molecule MAP4K4 inhibitor in Apoe−/− and Ldlr−/− mice, NF-κB nuclear localization and activity assays in cultured ECs Nature communications High 26688060
2015 Inducible whole-body Map4k4 deletion in obese mice improves insulin sensitivity in liver and adipose tissue but not skeletal muscle. Deletion of Map4k4 specifically in Myf5-positive tissues (skeletal muscle) is sufficient to protect from obesity-induced glucose intolerance, and also unexpectedly increases insulin sensitivity in adipose tissue. Tamoxifen-inducible whole-body Cre/ERT2 Map4k4 floxed knockout, tissue-specific conditional knockouts (adiponectin-Cre, albumin-Cre, Myf5-Cre), insulin signaling (AKT phosphorylation) in multiple tissues Molecular and cellular biology High 25918248
2017 MAP4K4, MINK1 (MAP4K6), and TNIK (MAP4K7) act redundantly upstream of DLK/JNK signaling in neurons. Targeting all three (but not any one individually) is sufficient to protect neurons from degeneration. MAP4K4/MINK1/TNIK pharmacological inhibition blocks DLK stabilization/phosphorylation within axons and prevents retrograde translocation of the JNK signaling complex to the nucleus. siRNA/pharmacological inhibition in mouse DRG neurons (trophic factor withdrawal model), DLK phosphorylation assays, retrograde signaling analysis, cell viability assays The Journal of neuroscience High 28993483
2017 Alternative splicing of MAP4K4 exon 16, regulated by SRSF3 in a sequence-dependent manner (with RBM4 as an upstream regulator of SRSF3 splicing), generates MAP4K4 variants with differential effects on JNK1 phosphorylation, which modulates E-cadherin, N-cadherin, and vimentin expression and alters migration/invasion of colorectal cancer cells. Transcriptome analysis of CRC tissues, SRSF3 splicing manipulation, MAP4K4 exon 16 inclusion/exclusion constructs, JNK1 phosphorylation assays, EMT marker expression, migration/invasion assays Biochimica et biophysica acta. Molecular cell research Medium 29138007
2017 MAP4K4 is a novel positive regulator of MAPK/ERK signaling in lung adenocarcinoma that activates ERK through inhibiting protein phosphatase 2 (PP2A) activity. MAP4K4 knockdown in lung adenocarcinoma cells, PP2A activity assay, ERK phosphorylation analysis, xenograft growth and metastasis assays Molecular oncology Medium 28306189
2019 MAP4K4 is activated in failing human hearts and by oxidative stress. MAP4K4 is required for oxidative stress-induced cardiomyocyte death. Pharmacological inhibition with DMX-5804 rescues cell survival, mitochondrial function, and calcium cycling in hiPSC-CMs, and reduces ischemia-reperfusion injury in mice by >50%. MAP4K4 gene silencing in hiPSC-CMs, small-molecule inhibitor (DMX-5804), oxidative stress assays, mitochondrial function, calcium cycling measurement, mouse ischemia-reperfusion model Cell stem cell High 30853557
2019 MAP4K4 activation regulates motor neuron degeneration in ALS via phosphorylated JNK3 and activation of the canonical c-Jun apoptotic pathway. MAP4K4 suppression promotes survival, prevents neurite degeneration, and decreases mutant SOD1 levels through autophagy (FoxO1-mediated) activation. MAP4K4 knockdown and pharmacological inhibition in ESC/iPSC-derived motor neurons and primary mouse spinal cord MNs, JNK3 phosphorylation assays, c-Jun pathway analysis, autophagy assays, SOD1 aggregate quantification Cell reports High 30699345
2020 STRIPAK complex member STRN4 is required for SV40 Small T antigen (ST)-PP2A-induced cell transformation. ST recruits STRIPAK (via striatin B''' subunits), which directs PP2A-mediated dephosphorylation of MAP4K4, activating the Hippo pathway effector YAP1 and promoting oncogenic transformation. ST-PP2A interaction proteomics, STRN4 knockdown transformation assays, MAP4K4 phosphorylation analysis, YAP1 activity assays eLife High 31913126
2020 MAP4K4 negatively regulates LFA-1 activation on CD8 T cells through ERM (ezrin, radixin, moesin) proteins, which serve as mediators between MAP4K4 and LFA-1. MAP4K4 deletion or inhibition enhances LFA-1 activation, improves T cell adherence to APCs, and increases CD8 T cell priming, proliferation, cytokine production, and cytotoxic activity. LFA-1 inhibition reverses these phenotypes. Genetic deletion (inducible whole-body Map4k4 KO), pharmacological inhibition, LFA-1 activation assays, T cell-APC conjugation assays, antitumor and antiviral in vivo models, LFA-1 inhibitor epistasis Science immunology High 32220977
2021 MAP4K4 directly phosphorylates MLK3 on Thr738, increasing MLK3 kinase activity and downstream signaling, thereby promoting pancreatic cancer cell proliferation, migration, and colony formation. MAP4K4 and MLK3 co-immunoprecipitate. Co-immunoprecipitation, direct phosphorylation assay (Thr738 site-specific), cell proliferation and migration assays, pharmacological MAP4K4 inhibitor (GNE-495) in KPC mouse model Oncogene High 34511598
2021 MAP4K4 is regulated within STRIPAK complexes in cardiomyocytes. FLAG-MAP4K4 associates with all three striatins (STRN1, STRN3, STRN4) and with myosin. Calyculin A (Ser/Thr phosphatase inhibitor) induces MAP4K4 hyperphosphorylation of the activation loop and linker region in a kinase-activity-dependent manner. Surprisingly, FLAG-MAP4K4 inhibits JNK activation by H2O2 in cardiomyocytes and increases myofibrillar organization. 5'-RACE and full-length cloning of rat Map4k4, FLAG-MAP4K4 co-immunoprecipitation with striatins and myosin, calyculin A treatment, phosphorylation mapping, kinase-dead mutant, JNK activation assay, myofibrillar staining The Biochemical journal Medium 34032269
2022 MAP4K4 interacts with striatin 3 (STRN3) via its CNH domain; STRN3 couples MAP4K4 to PP2A, which inactivates growth-repressing activities of MAP4K4. STRN3 also enables growth factor-induced PKCθ activation and direct phosphorylation of VASP-S157 by MAP4K4, which is required for efficient tumor cell invasion. Loss of STRN3 reactivates Hippo signaling. Co-immunoprecipitation (MAP4K4-STRN3/4), CNH domain deletion constructs, STRN3 and MAP4K4 depletion, VASP-S157 phosphorylation assay, PKCθ activation assay, Hippo pathway (YAP) activity, invasion assays in cerebellar tissue Communications biology High 35941177
2022 RhoA counteracts abdominal aortic aneurysm formation by inhibiting MAP4K4 activity. In the absence of RhoA, the PP2A inhibitor Set sequesters PP2A, releasing MAP4K4 from inhibition and activating MAP kinase signaling including MAP4K4. MAP4K4 inhibitor (DMX-5804) decreases AAA formation in RhoA cKO mice. VSMC-specific RhoA conditional knockout mice, MAP4K4 activity measurement, Set-PP2A interaction assays, DMX-5804 pharmacological inhibition, aortic ring contractility, gene expression Communications biology Medium 36207400
2023 MAP4K4 promotes ovarian cancer metastasis by phosphorylating ADAM10 at Ser436, which suppresses ADAM10-mediated cleavage of N-cadherin, leading to N-cadherin stabilization and enhanced cancer cell adhesion, migration, and invasion. MAP4K4 knockdown/overexpression, ADAM10 phosphorylation at Ser436 (site-specific), N-cadherin cleavage assays, cell adhesion/migration/invasion assays, pharmacological MAP4K4 inhibition in peritoneal metastasis model Oncogene High 36922678
2023 MAP4K4 regulates forces at cell-cell and cell-substrate adhesions to promote collective cell migration. MAP4K4 promotes focal adhesion disassembly through moesin phosphorylation but disassembles adherens junctions through a moesin-independent mechanism. Loss of MAP4K4 increases traction forces and tension at cell-cell adhesions, causing tensional disequilibrium in migrating clusters. MAP4K4 inactivation and overexpression in A431 carcinoma cells, traction force microscopy, intercellular force measurement, moesin phosphorylation assay, focal adhesion and adherens junction dynamics Life science alliance Medium 37369604
2024 MAP4K4 promotes S-nitrosylation of Drp1 (SNO-Drp1) at Cys644 (human C644/mouse C650) in cardiac microvascular endothelial cells by inhibiting GPX4 expression, which stimulates endothelial ferroptosis and cardiac microvascular dysfunction in diabetes. MAP4K4 inhibition (DMX-5804) reduces SNO-Drp1, alleviates microvascular dysfunction, and improves cardiac function in db/db mice; C650A Drp1 mutation abolishes SNO-Drp1 and its pathological effects. MAP4K4 overexpression/inhibition in CMECs, SNO-Drp1 site-specific analysis (C644/C650A mutation), GPX4 expression assay, ferroptosis assays, DMX-5804 in db/db mice, cardiac functional readouts Cardiovascular diabetology High 38724987
2018 HGK (MAP4K4) activation by the diterpenoid Tanshinone IIA triggers JNK1-dependent c-Jun activation, leading to increased c-Jun recruitment to the AP-1-binding site in the sestrin 2 (SESN2) promoter and upregulation of SESN2 transcription. This SESN2-dependent (but Beclin 1-independent) autophagy mediates the antitumor effects of TIIA in osteosarcoma. ChIP assay (c-Jun at SESN2 promoter), HGK/JNK1/Jun pathway dissection, autophagy assays (SESN2-dependent vs Beclin 1-dependent), in vitro and in vivo (NOD/SCID) osteosarcoma models Cell death & disease Medium 30258193
2016 MAP4K4 promotes NFκB signaling and MAP4K4 silencing in hepatocellular carcinoma cells represses JNK, NFκB, and toll-like receptor signaling pathways. In vitro, MAP4K4 knockdown reduces proliferation, blocks cell cycle at S phase, and increases apoptosis. shRNA knockdown in HCC cell lines, quantitative real-time PCR arrays for signaling pathway analysis, cell cycle analysis, apoptosis assay, xenograft tumor growth Clinical cancer research Medium 21196414
2013 MAP4K4 is required for KSHV lytic reactivation from latency and promotes invasiveness of KSHV-infected endothelial cells by regulating expression of COX-2, MMP-7, and MMP-13. Small molecule library screening and siRNA silencing in KSHV-infected endothelial cells, COX-2/MMP expression assays, invasion assays PLoS pathogens Medium 24244164
2013 MAP4K4 interacts with Pyk2 via the Pyk2 FERM domain, co-immunoprecipitates with Pyk2 (but not FAK), and is a substrate for Pyk2. MAP4K4 knockdown inhibits glioma cell migration and blocks Pyk2 stimulation of cell migration; MAP4K4 overexpression-stimulated migration is blocked by Pyk2 knockdown, indicating mutual dependence. Yeast two-hybrid screen, co-immunoprecipitation, in vitro substrate assay (Pyk2 phosphorylates MAP4K4), siRNA knockdown, cell migration assays Journal of signal transduction Medium 24163766
2021 MAP4K4 directly controls integrin β1 activation and c-Met endocytosis in medulloblastoma cells, promoting receptor recycling that accumulates activated c-Met in cytosolic vesicles and sustains downstream signaling. MAP4K4 depletion restricts HGF-driven matrix invasion in vitro and brain tissue infiltration ex vivo. MAP4K4 siRNA depletion, HGF-stimulated invasion and 3D migration assays, integrin β1 activation assay, c-Met endocytosis and recycling measurement, ex vivo brain slice infiltration Oncotarget Medium 29796184
2024 Dipeptide transport by PEPT1 activates the MAP4K4/G3BP2 signaling pathway in hepatocellular carcinoma cells, leading to phosphorylation of G3BP2 at Thr227 by MAP4K4, which facilitates HCC metastasis. PEPT1 overexpression/knockdown, MAP4K4/G3BP2 pathway analysis, G3BP2-Thr227 phosphorylation assay, migration/invasion assays, lung metastasis mouse model Advanced science Medium 38639383

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2009 Orally delivered siRNA targeting macrophage Map4k4 suppresses systemic inflammation. Nature 455 19407801
2006 A small interfering RNA screen for modulators of tumor cell motility identifies MAP4K4 as a promigratory kinase. Proceedings of the National Academy of Sciences of the United States of America 168 16537454
1999 A novel human STE20-related protein kinase, HGK, that specifically activates the c-Jun N-terminal kinase signaling pathway. The Journal of biological chemistry 153 9890973
2006 An RNA interference-based screen identifies MAP4K4/NIK as a negative regulator of PPARgamma, adipogenesis, and insulin-responsive hexose transport. Proceedings of the National Academy of Sciences of the United States of America 135 16461467
2013 miRNA-141, downregulated in pancreatic cancer, inhibits cell proliferation and invasion by directly targeting MAP4K4. Molecular cancer therapeutics 128 24013097
2007 MAP4K4 gene silencing in human skeletal muscle prevents tumor necrosis factor-alpha-induced insulin resistance. The Journal of biological chemistry 117 17227768
2015 MAP4K4 regulates integrin-FERM binding to control endothelial cell motility. Nature 116 25799996
2012 MicroRNA-30d induces insulin transcription factor MafA and insulin production by targeting mitogen-activated protein 4 kinase 4 (MAP4K4) in pancreatic β-cells. The Journal of biological chemistry 113 22733810
2003 The STE20 kinase HGK is broadly expressed in human tumor cells and can modulate cellular transformation, invasion, and adhesion. Molecular and cellular biology 107 12612079
2013 Galactosylated trimethyl chitosan-cysteine nanoparticles loaded with Map4k4 siRNA for targeting activated macrophages. Biomaterials 103 23419643
2014 Microtubules regulate focal adhesion dynamics through MAP4K4. Developmental cell 101 25490267
2015 Endothelial protein kinase MAP4K4 promotes vascular inflammation and atherosclerosis. Nature communications 95 26688060
2010 ShRNA-targeted MAP4K4 inhibits hepatocellular carcinoma growth. Clinical cancer research : an official journal of the American Association for Cancer Research 90 21196414
2017 The Ste20 Family Kinases MAP4K4, MINK1, and TNIK Converge to Regulate Stress-Induced JNK Signaling in Neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 87 28993483
1990 Expression of the gene coding for human prostate-specific antigen and related hGK-1 in benign and malignant tumors of the human prostate. International journal of cancer 85 1691151
2013 SOX2 regulates apoptosis through MAP4K4-survivin signaling pathway in human lung cancer cells. Carcinogenesis 84 24233838
2014 HGK/MAP4K4 deficiency induces TRAF2 stabilization and Th17 differentiation leading to insulin resistance. Nature communications 77 25098764
1995 Isolation of prostatic kallikrein hK2, also known as hGK-1, in human seminal plasma. Biochimica et biophysica acta 77 8541306
1991 Identification and androgen-regulated expression of two major human glandular kallikrein-1 (hGK-1) mRNA species. Molecular and cellular endocrinology 75 1726490
2023 Histone lactylation-derived LINC01127 promotes the self-renewal of glioblastoma stem cells via the cis-regulating the MAP4K4 to activate JNK pathway. Cancer letters 73 38084701
2019 MAP4K4 Inhibition Promotes Survival of Human Stem Cell-Derived Cardiomyocytes and Reduces Infarct Size In Vivo. Cell stem cell 73 30853557
2016 MAP4K4: an emerging therapeutic target in cancer. Cell & bioscience 73 27800153
2007 Tumor necrosis factor alpha (TNFalpha) stimulates Map4k4 expression through TNFalpha receptor 1 signaling to c-Jun and activating transcription factor 2. The Journal of biological chemistry 73 17500068
2015 MiR-194, commonly repressed in colorectal cancer, suppresses tumor growth by regulating the MAP4K4/c-Jun/MDM2 signaling pathway. Cell cycle (Georgetown, Tex.) 72 25602366
2018 Downregulated miR-98-5p promotes PDAC proliferation and metastasis by reversely regulating MAP4K4. Journal of experimental & clinical cancer research : CR 70 29970191
2017 FGFR1 is critical for the anti-endothelial mesenchymal transition effect of N-acetyl-seryl-aspartyl-lysyl-proline via induction of the MAP4K4 pathway. Cell death & disease 61 28771231
2019 MAP4K4 Activation Mediates Motor Neuron Degeneration in Amyotrophic Lateral Sclerosis. Cell reports 59 30699345
2020 Silencing of Long Non-coding RNA GAS5 Suppresses Neuron Cell Apoptosis and Nerve Injury in Ischemic Stroke Through Inhibiting DNMT3B-Dependent MAP4K4 Methylation. Translational stroke research 58 31997156
2021 MAP4K4 mediates the SOX6-induced autophagy and reduces the chemosensitivity of cervical cancer. Cell death & disease 57 34930918
2021 The membrane-localized protein kinase MAP4K4/TOT3 regulates thermomorphogenesis. Nature communications 51 33990595
2017 RBM4-SRSF3-MAP4K4 splicing cascade modulates the metastatic signature of colorectal cancer cell. Biochimica et biophysica acta. Molecular cell research 51 29138007
2017 MAP4K4 is a novel MAPK/ERK pathway regulator required for lung adenocarcinoma maintenance. Molecular oncology 50 28306189
2008 RNAi screens reveal novel metabolic regulators: RIP140, MAP4k4 and the lipid droplet associated fat specific protein (FSP) 27. Acta physiologica (Oxford, England) 50 18171433
2018 HGK-sestrin 2 signaling-mediated autophagy contributes to antitumor efficacy of Tanshinone IIA in human osteosarcoma cells. Cell death & disease 48 30258193
2009 Silencing mitogen-activated protein 4 kinase 4 (MAP4K4) protects beta cells from tumor necrosis factor-alpha-induced decrease of IRS-2 and inhibition of glucose-stimulated insulin secretion. The Journal of biological chemistry 48 19690174
1989 hGK-1: a kallikrein gene expressed in human prostate. Clinical and experimental pharmacology & physiology 47 2472912
2020 STRIPAK directs PP2A activity toward MAP4K4 to promote oncogenic transformation of human cells. eLife 46 31913126
2019 Targeted genomic CRISPR-Cas9 screen identifies MAP4K4 as essential for glioblastoma invasion. Scientific reports 46 31570734
2022 Transcriptome profiling of microRNAs reveals potential mechanisms of manual therapy alleviating neuropathic pain through microRNA-547-3p-mediated Map4k4/NF-κb signaling pathway. Journal of neuroinflammation 40 36045396
2014 Discovery of selective 4-Amino-pyridopyrimidine inhibitors of MAP4K4 using fragment-based lead identification and optimization. Journal of medicinal chemistry 39 24673130
2013 The inflammatory kinase MAP4K4 promotes reactivation of Kaposi's sarcoma herpesvirus and enhances the invasiveness of infected endothelial cells. PLoS pathogens 38 24244164
2015 Structure-Based Design of GNE-495, a Potent and Selective MAP4K4 Inhibitor with Efficacy in Retinal Angiogenesis. ACS medicinal chemistry letters 37 26288693
2015 Discovery of an in Vivo Tool to Establish Proof-of-Concept for MAP4K4-Based Antidiabetic Treatment. ACS medicinal chemistry letters 37 26617966
2020 LncRNA LINC01857 promotes cell growth and diminishes apoptosis via PI3K/mTOR pathway and EMT process by regulating miR-141-3p/MAP4K4 axis in diffuse large B-cell lymphoma. Cancer gene therapy 36 33311569
2016 Map4k4 Signaling Nodes in Metabolic and Cardiovascular Diseases. Trends in endocrinology and metabolism: TEM 36 27160798
2015 Silencing SOX2 Expression by RNA Interference Inhibits Proliferation, Invasion and Metastasis, and Induces Apoptosis through MAP4K4/JNK Signaling Pathway in Human Laryngeal Cancer TU212 Cells. The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society 36 26001828
2015 Silencing of MAP4K4 by short hairpin RNA suppresses proliferation, induces G1 cell cycle arrest and induces apoptosis in gastric cancer cells. Molecular medicine reports 34 26549737
2024 MAP4K4 exacerbates cardiac microvascular injury in diabetes by facilitating S-nitrosylation modification of Drp1. Cardiovascular diabetology 33 38724987
2019 MAP4K4 associates with BIK1 to regulate plant innate immunity. EMBO reports 33 31475431
2015 Neuritogenic militarinone-inspired 4-hydroxypyridones target the stress pathway kinase MAP4K4. Angewandte Chemie (International ed. in English) 33 25908259
2009 Map4k4 negatively regulates peroxisome proliferator-activated receptor (PPAR) gamma protein translation by suppressing the mammalian target of rapamycin (mTOR) signaling pathway in cultured adipocytes. The Journal of biological chemistry 33 20038583
2013 Map4k4 suppresses Srebp-1 and adipocyte lipogenesis independent of JNK signaling. Journal of lipid research 32 23924694
2021 MAP4K4 promotes pancreatic tumorigenesis via phosphorylation and activation of mixed lineage kinase 3. Oncogene 30 34511598
2018 MAP4K4 controlled integrin β1 activation and c-Met endocytosis are associated with invasive behavior of medulloblastoma cells. Oncotarget 27 29796184
2016 MAP4K4 promotes epithelial-mesenchymal transition and metastasis in hepatocellular carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 27 27010469
2012 Identification of Map4k4 as a novel suppressor of skeletal muscle differentiation. Molecular and cellular biology 27 23207904
2015 Inducible Deletion of Protein Kinase Map4k4 in Obese Mice Improves Insulin Sensitivity in Liver and Adipose Tissues. Molecular and cellular biology 26 25918248
2012 Association of common genetic variants in the MAP4K4 locus with prediabetic traits in humans. PloS one 25 23094072
2015 The Ser/Thr kinase MAP4K4 drives c-Met-induced motility and invasiveness in a cell-based model of SHH medulloblastoma. SpringerPlus 24 25625039
2020 MAP4K4 negatively regulates CD8 T cell-mediated antitumor and antiviral immunity. Science immunology 22 32220977
2013 A Novel Interaction between Pyk2 and MAP4K4 Is Integrated with Glioma Cell Migration. Journal of signal transduction 22 24163766
2024 MAP4K4 and WT1 mediate SOX6-induced cellular senescence by synergistically activating the ATF2-TGFβ2-Smad2/3 signaling pathway in cervical cancer. Molecular oncology 21 38383842
2023 Molecular Insights of MAP4K4 Signaling in Inflammatory and Malignant Diseases. Cancers 21 37190200
2022 MAP4K4 controlled transcription factor POUM1 regulates PxABCG1 expression influencing Cry1Ac resistance in Plutella xylostella (L.). Pesticide biochemistry and physiology 21 35249643
2015 Cellular MicroRNA Let-7a Suppresses KSHV Replication through Targeting MAP4K4 Signaling Pathways. PloS one 21 26197270
2014 Fragment-based identification and optimization of a class of potent pyrrolo[2,1-f][1,2,4]triazine MAP4K4 inhibitors. Bioorganic & medicinal chemistry letters 21 25139565
2023 MAP4K4 promotes ovarian cancer metastasis through diminishing ADAM10-dependent N-cadherin cleavage. Oncogene 20 36922678
2022 Intestinal epithelial cell-derived exosomes package microRNA-23a-3p alleviate gut damage after ischemia/reperfusion via targeting MAP4K4. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 20 35303564
2018 MicroRNA-200c suppressed cervical cancer cell metastasis and growth via targeting MAP4K4. European review for medical and pharmacological sciences 20 29461619
2022 MiR-181c suppresses triple-negative breast cancer tumorigenesis by targeting MAP4K4. Pathology, research and practice 19 35026645
2020 Selective protection of human cardiomyocytes from anthracycline cardiotoxicity by small molecule inhibitors of MAP4K4. Scientific reports 19 32694738
2018 RBM4a-SRSF3-MAP4K4 Splicing Cascade Constitutes a Molecular Mechanism for Regulating Brown Adipogenesis. International journal of molecular sciences 19 30200638
2014 MAP4K4 deletion inhibits proliferation and activation of CD4(+) T cell and promotes T regulatory cell generation in vitro. Cellular immunology 19 24681727
2016 Epigenetic regulation of HGK/MAP4K4 in T cells of type 2 diabetes patients. Oncotarget 18 26918832
2016 MAP4K4 deficiency in CD4(+) T cells aggravates lung damage induced by ozone-oxidized black carbon particles. Environmental toxicology and pharmacology 18 27504712
2021 MAP4K4 induces early blood-brain barrier damage in a murine subarachnoid hemorrhage model. Neural regeneration research 17 32859792
2021 RETRACTED: Mouse bone marrow derived mesenchymal stem cells-secreted exosomal microRNA-125b-5p suppresses atherosclerotic plaque formation via inhibiting Map4k4. Life sciences 17 33652034
2018 Role of TLR4-MAP4K4 signaling pathway in models of oxygen-induced retinopathy. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 16 30475644
2016 Protein Kinase Mitogen-activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Promotes Obesity-induced Hyperinsulinemia. The Journal of biological chemistry 16 27226575
2022 The molecular basis of the dichotomous functionality of MAP4K4 in proliferation and cell motility control in cancer. Frontiers in oncology 15 36568222
2017 Association of MAP4K4 gene single nucleotide polymorphism with mastitis and milk traits in Chinese Holstein cattle. The Journal of dairy research 15 28252361
2022 Vascular smooth muscle RhoA counteracts abdominal aortic aneurysm formation by modulating MAP4K4 activity. Communications biology 14 36207400
2021 Preclinical trial of a MAP4K4 inhibitor to reduce infarct size in the pig: does cardioprotection in human stem cell-derived myocytes predict success in large mammals? Basic research in cardiology 14 34018053
2015 MAP4K4 Is a Threonine Kinase That Phosphorylates FARP1. ACS chemical biology 14 26422651
2022 LncRNA ZEB1-AS1/miR-1224-5p / MAP4K4 axis regulates mitochondria-mediated HeLa cell apoptosis in persistent Chlamydia trachomatis infection. Virulence 13 35266440
2022 Inhibition of MAP4K4 signaling initiates metabolic reprogramming to protect hepatocytes from lipotoxic damage. Journal of lipid research 13 35679904
2022 Cooperation of Striatin 3 and MAP4K4 promotes growth and tissue invasion. Communications biology 13 35941177
2022 MAP4K4/JNK Signaling Pathway Stimulates Proliferation and Suppresses Apoptosis of Human Spermatogonial Stem Cells and Lower Level of MAP4K4 Is Associated with Male Infertility. Cells 13 36497065
2021 A new function for MAP4K4 inhibitors during platelet aggregation and platelet-mediated clot retraction. Biochemical pharmacology 13 33737052
2019 Suppression of MAP4K4 Signaling Ameliorates Motor Neuron Degeneration in Amyotrophic Lateral Sclerosis-Molecular Studies Toward New Therapeutics. Journal of experimental neuroscience 12 31320806
2018 Function of microRNA‑141 in human breast cancer through cytotoxic CD4+ T cells regulated by MAP4K4 expression. Molecular medicine reports 12 29620289
2017 MAP4K4 and IL-6+ Th17 cells play important roles in non-obese type 2 diabetes. Journal of biomedical science 12 28061846
2017 Map4k4 impairs energy metabolism in endothelial cells and promotes insulin resistance in obesity. American journal of physiology. Endocrinology and metabolism 12 28611026
2010 Lowered HGK expression inhibits cell invasion and adhesion in hepatocellular carcinoma cell line HepG2. World journal of gastroenterology 12 20857524
2018 Chemotherapy-induced miR-141/MAP4K4 signaling suppresses progression of colorectal cancer. Bioscience reports 11 30429233
2023 MAP4K4 regulates forces at cell-cell and cell-matrix adhesions to promote collective cell migration. Life science alliance 10 37369604
2021 MAP4K4 expression in cardiomyocytes: multiple isoforms, multiple phosphorylations and interactions with striatins. The Biochemical journal 10 34032269
2024 Peptide Transporter 1-Mediated Dipeptide Transport Promotes Hepatocellular Carcinoma Metastasis by Activating MAP4K4/G3BP2 Signaling Axis. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 9 38639383
2021 HGK promotes metastatic dissemination in prostate cancer. Scientific reports 9 34112843
2018 2-Aminopyridine-Based Mitogen-Activated Protein Kinase Kinase Kinase Kinase 4 (MAP4K4) Inhibitors: Assessment of Mechanism-Based Safety. Journal of medicinal chemistry 9 29570292

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