Affinage

MAPK14

Mitogen-activated protein kinase 14 · UniProt Q16539

Length
360 aa
Mass
41.3 kDa
Annotated
2026-06-10
100 papers in source corpus 45 papers cited in narrative 45 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 7/7 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAPK14/p38α is a stress- and signal-activated serine/threonine protein kinase that coordinates inflammation, cell proliferation versus differentiation, autophagy, metabolism, and tissue homeostasis through direct phosphorylation of a broad substrate repertoire (PMID:17468757, PMID:23235332, PMID:37202506). Its catalytic activation is achieved by two structurally defined routes: canonical dual phosphorylation of the activation segment by MKK6 through a dynamic multistep mechanism whose MAP2K disordered N-terminus dictates pathway specificity (PMID:37708276), and a non-canonical cis-autophosphorylation driven by direct TAB1 docking at a bipartite C-lobe site that stabilizes the active conformation and extends the Thr-Gly-Tyr segment, with this autoactivation requiring an intramolecular Thr185–Asp150 hydrogen bond and being central to ischemic cardiac injury (PMID:24037507, PMID:30135318, PMID:29229647). Activation requires Thr180 as the dominant activating phosphosite (PMID:24393126), and substrate docking—exemplified by MK2—allosterically accelerates catalysis beyond simple anchoring (PMID:25038803). Through these mechanisms p38α phosphorylates ATG5-T75, ULK1-S555, FOXO1-S273, Ube3c-S741, CtIP, KMT1A, TAB1, and HSP27 (via the PAK→p38α→MK2→HSP27 migration axis) to control autophagy and mitophagy, gluconeogenesis and glucose metabolism, DNA repair, myogenic chromatin remodeling, cell migration, and uterine implantation (PMID:14592977, PMID:16574378, PMID:23235332, PMID:27551368, PMID:29805078, PMID:31092814, PMID:35914132, PMID:37202506). In its tissue roles p38α acts as a context-dependent brake on proliferation by antagonizing the JNK–c-Jun axis and tuning EGFR signaling in progenitor cells (PMID:17468757, PMID:17468755, PMID:30541887), yet drives malignant proliferation, fibrosis, steatohepatitis, and pre-metastatic niche formation in other settings through effectors such as TIMP-1, IGF-1, FAP, and NF-κB (PMID:30914267, PMID:29907597, PMID:31969449, PMID:34124690, PMID:30771750). Its activity is terminated by MKP1-mediated dephosphorylation, which permits fibrosis resolution (PMID:38512415). A kidney-restricted splice isoform, Mxi2, differs only in its C-terminus, escapes MKK3/6 activation and ATF2 phosphorylation, shows altered inhibitor and phosphatase sensitivity, and instead binds ERK1/2 to selectively sustain nuclear ERK signaling (PMID:7479834, PMID:10751326, PMID:10838079, PMID:12697810).

Mechanistic history

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

    Established that a p38α splice isoform (Mxi2) carries intrinsic kinase activity directed at a specific transcription factor, raising the question of isoform-specific substrate recognition.

    Evidence Yeast two-hybrid plus in vitro/in vivo phosphorylation of Max

    PMID:7479834

    Open questions at the time
    • Physiological relevance of Max phosphorylation in vivo not established
    • Substrate-recognition motif inferred from sequence similarity, not structurally proven
  2. 2000 Medium

    Defined the unique C-terminus of Mxi2 as the determinant of its divergent regulation, showing it cannot be activated by MKK3/6 or phosphorylate ATF2 and is kidney-restricted, distinguishing it functionally from p38α.

    Evidence Immunohistochemistry, kinase assays, and domain-swap hybrids

    PMID:10751326 PMID:10838079

    Open questions at the time
    • In vivo function of kidney Mxi2 unresolved
    • Physiological activator of Mxi2 unknown
  3. 2003 Medium

    Revealed that Mxi2 acts as an ERK scaffold, physically binding ERK1/2 to prolong specifically nuclear ERK signaling, connecting the p38 locus to cross-pathway control.

    Evidence Reciprocal co-IP, reporter assays, Ras/Raf/MEK epistasis

    PMID:12697810

    Open questions at the time
    • Mechanism by which Mxi2 selectively protects nuclear ERK unclear
    • Structural basis of the Mxi2–ERK interaction not solved
  4. 2003 High

    Identified TAB1 as a direct p38α substrate phosphorylated at mapped sites, establishing a negative feedback loop limiting TAK1 and coordinating p38α with JNK/IKK pathways.

    Evidence In vitro kinase assay with mapped sites, p38α-knockout MEFs, TAK1 activity assays

    PMID:14592977

    Open questions at the time
    • Quantitative contribution of feedback to in vivo signaling not defined
  5. 2004 High

    Demonstrated that conformational changes near the L16 loop alone can confer high intrinsic activity, mechanistically separating activation from upstream phosphorylation.

    Evidence Active-site mutants with biochemical kinase assays and structural interpretation

    PMID:15284239

    Open questions at the time
    • Whether equivalent conformational states occur physiologically not addressed
  6. 2006 High

    Catalogued the multiple activation modes of p38α—canonical MKK3/6, TAB1-mediated autophosphorylation, and peroxynitrite-induced disulfide complexes—and placed p38α in a defined migration pathway (PAK→p38α→MK2→HSP27).

    Evidence MKK double-knockout MEFs, cysteine mutagenesis, isoform-specific knockout and RNAi in migration assays

    PMID:16574378 PMID:16849316

    Open questions at the time
    • Identity of the ~85-kDa peroxynitrite partner unresolved
    • Relative weighting of activation modes across tissues unknown
  7. 2007 High

    Defined p38α as a context-dependent suppressor of proliferation, antagonizing the JNK–c-Jun axis and tuning EGFR-driven progenitor self-renewal.

    Evidence Conditional Mapk14 knockout in multiple cell types with JNK/c-Jun epistasis and differentiation assays

    PMID:17468755 PMID:17468757

    Open questions at the time
    • Direct substrates linking p38α to JNK/c-Jun suppression not all identified
    • Tissue-specific switch between suppressor and promoter roles not mechanistically explained
  8. 2009 High

    Identified a C-lobe lipid-binding pocket around Trp197 distinct from the ATP site, expanding the allosteric ligand landscape of p38α.

    Evidence X-ray crystallography with bound ligand and computational analysis

    PMID:19501598

    Open questions at the time
    • Endogenous lipid ligand of the pocket not identified
    • Functional consequence of pocket occupancy in cells untested
  9. 2012 High

    Showed that activator-specific p38α (via GADD45B-MAP3K4) localizes to autophagosomes and phosphorylates ATG5-T75 to block autophagosome–lysosome fusion, linking p38α to autophagy regulation and chemoresistance.

    Evidence Subcellular fractionation, in vitro kinase with mapped site, mutant reconstitution in knockout cells; plus siRNA/inhibitor work in TP53-null colon cancer

    PMID:22647487 PMID:23235332

    Open questions at the time
    • How activator identity dictates p38α autophagosome targeting unclear
    • Direction of autophagy effect varies by context
  10. 2013 High

    Solved the structural basis of TAB1-driven cis-autophosphorylation and connected it causally to myocardial ischemic injury and to cardiac contractility via PP2A/PP1/phospholamban.

    Evidence Crystallography, chemical-genetics, cell-free reconstitution, ex vivo cardiomyocyte and perfused-heart models; phosphatase activity assays

    PMID:24037507 PMID:24361238

    Open questions at the time
    • Direct substrate(s) of p38α driving the contractility phenotype not fully mapped
    • PRMT1-mediated methylation of p38α (PMID 23483889) regulatory role incompletely defined
  11. 2014 High

    Defined the activating chemistry and allostery of p38α—Thr180 as the dominant activating phosphosite and substrate docking (MK2) that accelerates phosphotransfer—while extending p38α to glucose metabolic reprogramming.

    Evidence Semisynthetic phosphorylation, solution NMR, in vitro kinase kinetics; metabolic flux assays and PFKFB3 degron mutagenesis

    PMID:24393126 PMID:25038803 PMID:25046111

    Open questions at the time
    • In vivo dominance of Thr180 over Tyr182 not directly tested
    • Mechanism coupling p38α to HIF1A stabilization not fully resolved
  12. 2015 High

    Established hepatic and organelle-level metabolic roles: p38α restrains AMPK to sustain fasting gluconeogenesis and is required for starvation/hypoxia mitophagy via the alternative RAB9 pathway.

    Evidence Liver-specific knockout with dominant-negative AMPK epistasis; Keima mitophagy assay with knockdown and Atg5-KO controls

    PMID:25595884 PMID:25831013 PMID:26061537

    Open questions at the time
    • Direct p38α substrate in AMPK feedback not identified
    • Pyridinyl-imidazole inhibitors confound pharmacological dissection of p38-autophagy link
  13. 2016 High

    Linked p38α to chromatin remodeling, showing it phosphorylates KMT1A to displace it from MyoD and reprogram H3K9 marks at the Myogenin promoter during myogenesis.

    Evidence In vitro kinase, co-IP, ChIP for H3K9me3/ac, gain- and loss-of-function

    PMID:27551368

    Open questions at the time
    • KMT1A phosphosite(s) not mapped here
    • Generalizability to other lineage-specifying loci untested
  14. 2018 High

    Refined the cis-autoactivation mechanism to an intramolecular Thr185–Asp150 hydrogen bond and four TAB1 docking residues, enabling separation-of-function mutants that confer ischemia resistance, and added a DNA-repair substrate (CtIP).

    Evidence Crystallography, structure-guided T185G mutagenesis, TAB1 knock-in mice, cardiac injury models; conditional knockout/inhibition with HR repair and ATR assays

    PMID:29229647 PMID:29805078 PMID:30135318

    Open questions at the time
    • CtIP phosphosite(s) not mapped
    • Therapeutic separation of autophosphorylation from canonical activity not yet translated
  15. 2019 High

    Mapped diverse tissue programs: ULK1-S555-dependent autophagy steering cells to senescence, and cell-type-specific pro-disease roles in immune, vascular, stromal, and cancer settings via NF-κB/NOX4, IGF-1, TGF-β/JNK, IL-27, and TIMP-1.

    Evidence Inducible activation systems with mapped ULK1-S555; multiple cell-type-specific conditional knockouts with pathway epistasis and tumor/injury models

    PMID:29907597 PMID:30541887 PMID:30771750 PMID:31092814 PMID:31296856 PMID:31969449

    Open questions at the time
    • Molecular basis for opposing tumor-suppressor versus tumor-promoter outcomes not unified
    • Direct substrates downstream of most tissue phenotypes unidentified
  16. 2021 Medium

    Showed constitutively active p38α is sufficient to cause reversible fatty liver and that SUMOylation at K152 modulates a nuclear p38α–MK2 ROS-sensing axis.

    Evidence Inducible active-allele transgenics with reversibility; SUMO site mapping by IP/pull-down with nuclear ROS readouts

    PMID:33811139 PMID:34686655

    Open questions at the time
    • SUMOylation mechanism single-lab, not independently confirmed
    • Substrates mediating the fatty-liver gene-expression program not defined
  17. 2022 High

    Extended the substrate-and-program map to plasma cell differentiation (BLIMP1 via TCF3/4/IRF4), uterine implantation (Ube3c-S741 protecting progesterone receptor), and dendritic-cell-controlled Th2 responses (MK2-c-FOS-IL-12).

    Evidence B-cell, uterine, and DC-specific conditional knockouts; CRISPR screen, reporter mice, in vitro kinase with LC-MS phosphosite mapping, ubiquitination assays

    PMID:35551270 PMID:35914132 PMID:36443297

    Open questions at the time
    • Direct BLIMP1-axis substrate of p38α not identified
    • Cross-tissue generality of the Ube3c regulatory mechanism unknown
  18. 2023 High

    Defined the dynamic multistep dual-phosphorylation mechanism by which MKK6 activates p38α and showed MAP2K N-termini dictate pathway specificity, while identifying FOXO1-S273 as a glucagon/EPAC2-driven hepatic substrate controlling glucose production.

    Evidence Cryo-EM with HDX-MS and MD validation; in vitro LC-MS phosphosite mapping with Foxo1-S273 knock-in mice and glucagon tolerance tests

    PMID:37202506 PMID:37708276

    Open questions at the time
    • Structural basis of substrate (versus activator) discrimination not fully generalized
  19. 2024 High

    Established MKP1-mediated dephosphorylation of p38α as the off-switch enabling fibrosis resolution and myofibroblast dedifferentiation.

    Evidence Fibroblast-specific MKP1 conditional knockout with VX-702 p38α inhibitor rescue in bleomycin fibrosis

    PMID:38512415

    Open questions at the time
    • p38α substrates driving myofibroblast persistence not mapped
  20. 2025 Medium

    Connected p38α nuclear translocation to p53-dependent transcription, showing a small molecule (lobeline) that blocks nuclear entry relieves p53 repression of SLURP1 to reprogram tumor macrophages.

    Evidence DARTS and target-responsive accessibility profiling, nuclear/cytoplasmic fractionation, p53 phosphorylation assays, Slurp1-deficient xenografts

    PMID:39840525

    Open questions at the time
    • Direct p53 phosphorylation by p38α site not mapped here
    • Single-lab binding/mechanism not independently replicated

Open questions

Synthesis pass · forward-looking unresolved questions
  • It remains unresolved what molecular features dictate p38α's opposing context-dependent outcomes (tumor suppressor versus promoter; pro- versus anti-autophagic) and how activator identity, subcellular localization, and post-translational modification combine to select specific substrate sets.
  • No unifying model linking upstream activator to downstream substrate selection
  • Direct substrates behind many tissue phenotypes still unidentified
  • Physiological role of the C-lobe lipid pocket and SUMOylation not established

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0016740 transferase activity 5 GO:0140096 catalytic activity, acting on a protein 5 GO:0140657 ATP-dependent activity 2
Localization
GO:0005634 nucleus 3 GO:0031410 cytoplasmic vesicle 1
Pathway
R-HSA-162582 Signal Transduction 4 R-HSA-168256 Immune System 4 R-HSA-1266738 Developmental Biology 3 R-HSA-1430728 Metabolism 3 R-HSA-9612973 Autophagy 3 R-HSA-73894 DNA Repair 1
Partners
ATG5ERK1/2FOXO1MK2MKK6PRMT1TAB1ULK1

Evidence

Reading pass · 45 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1995 Mxi2 (a splice isoform of p38α/MAPK14) interacts with Max protein and the C-terminus of c-Myc in yeast two-hybrid assays, and directly phosphorylates Max both in vitro and in vivo; the putative substrate recognition region of Mxi2 shares sequence similarity with the helix-loop-helix region of Max and c-Myc, suggesting substrate recognition via this motif. Yeast two-hybrid, in vitro and in vivo phosphorylation assays Proceedings of the National Academy of Sciences of the United States of America Medium 7479834
2000 Mxi2 (p38α splice isoform) lacks most of the XI domain of p38 and has a unique 17-amino acid C-terminus. It is expressed exclusively in the kidney (distal tubule) in mice. Unlike p38α, Mxi2 is not activated by MKK3 or MKK6 and cannot phosphorylate ATF-2; its unique COOH-terminus confers these distinct properties. Immunohistochemistry, kinase assay with ATF-2 substrate, domain-swap hybrid protein analysis American journal of physiology. Cell physiology Medium 10751326
2000 The C-terminus of p38α is a key determinant of inhibitor sensitivity (SB203580), substrate affinity, and phosphatase (CL100) sensitivity; Mxi2, which differs only in its C-terminus, shows greatly reduced substrate affinity, reduced sensitivity to SB203580, and its activity is largely unaffected by CL100. In vitro kinase assay, pharmacological inhibition, phosphatase assay FEBS letters Medium 10838079
2003 Mxi2 (p38α splice isoform) physically associates with ERK1/2 (co-immunoprecipitation in cells and in kidney) and sustains ERK phosphorylation levels, specifically prolonging the duration of ERK nuclear signaling (activating Elk1 and HIF1α) without affecting cytoplasmic ERK substrates RSK2 and cPLA2. Co-immunoprecipitation, kinase activity assays, reporter gene assays for Elk1 and HIF1α, genetic epistasis with Ras/Raf/MEK Molecular and cellular biology Medium 12697810
2003 SAPK2a/p38α directly phosphorylates TAB1 at Ser423, Thr431, and Ser438 in vitro (Ser423 is a non-proline-directed site). In cells, phosphorylation of Ser423 and Thr431 is blocked by the p38 inhibitor SB 203580. p38α-mediated TAB1 phosphorylation constitutes a negative feedback loop that limits TAK1 activation, thereby coordinating p38α activity with JNK and IKK pathways downstream of TAK1. In vitro kinase assay, pharmacological inhibition, p38α-knockout MEFs, TAK1 activity assays in cells The EMBO journal High 14592977
2004 Active mutants of human p38α (D176A, F327L, F327S, and double mutants) acquire high intrinsic kinase activity independent of upstream phosphorylation by destabilizing a hydrophobic core formed by Tyr69, Phe327, and Trp337 near the L16 loop, emulating conformational changes imposed by dual phosphorylation; these mutants retain substrate specificity and inhibitor sensitivity. Site-directed mutagenesis, in vitro kinase assay, structural analysis based on existing p38/ERK2 crystal structures The Journal of biological chemistry High 15284239
2006 p38α activation mediates cell migration induced by CXCL12, C5a, HGF, and PDGF-BB via a PAK1/2→p38α→MAPKAP-K2→HSP27 signaling pathway. Genetic ablation of p38α (but not other p38 isoforms) abolished migration; RNAi against MAPKAP-K2 or HSP27 also blocked migration, placing these downstream of p38α. Genetic knockout mice, pharmacological inhibition (SB203580, BIRB0796), RNAi knockdown, cell migration assays Cellular signalling High 16574378
2006 Multiple activation mechanisms of p38α exist in cells: (1) canonical MKK3/6-dependent phosphorylation (primary); (2) TAB1-mediated autophosphorylation independent of MKK3/4/6; (3) peroxynitrite-induced phosphorylation via a disulfide-bond complex involving a ~85-kDa binding partner of p38α. TAB1-mediated autophosphorylation did not require MKK3/4/6, and TAB1 inhibited p38α phosphorylation in the peroxynitrite-induced complex. MKK3/6 and MKK4/7 double-knockout MEFs, mutagenesis of p38α cysteines, immunoprecipitation, phospho-p38 immunoblotting The Journal of biological chemistry High 16849316
2007 p38α (MAPK14) suppresses cell proliferation by antagonizing the JNK–c-Jun pathway. In Mapk14-deficient embryonic fibroblasts, fetal hematopoietic cells, and hepatocytes, proliferation increased due to sustained JNK-c-Jun activation. Inactivation of JNK or c-Jun suppressed the increased proliferation of Mapk14-deficient cells, placing p38α as a negative regulator upstream of the JNK-c-Jun axis. Conditional Mapk14 knockout mice, genetic epistasis (JNK and c-Jun inactivation), cell proliferation assays Nature genetics High 17468757
2007 p38α positively regulates CCAAT/enhancer-binding protein expression required for lung cell differentiation, and controls self-renewal by inhibiting epidermal growth factor receptor-driven proliferation signals in lung stem/progenitor cells. Conditional p38α knockout mice (adult), in vivo and in vitro differentiation assays, signaling pathway analysis Nature genetics High 17468755
2009 p38α C-terminal cap (C-lobe) contains a lipid-binding pocket formed around residue Trp197; a lead compound binds both the active site and this C-terminal hydrophobic pocket, inducing movement of the C-terminal cap region. This pocket is structurally distinct from the ATP-binding site and can accommodate lipids, leukotrienes, and small-molecule effectors. X-ray crystallography, computational analysis Journal of molecular biology High 19501598
2012 MAPK14/p38α, when activated specifically by the GADD45B-MAP3K4 signaling complex (but not by other activators), localizes to autophagosomes and directly phosphorylates ATG5 at threonine 75, impairing autophagosome-lysosome fusion and thus inhibiting autophagic flux. ATG5 T75 phosphorylation-defective mutants show enhanced autophagy. Subcellular fractionation to autophagosomes, in vitro kinase assay, phosphorylation-defective and phosphomimetic ATG5 reconstitution, MAPK14-knockout and GADD45B-knockout cells Autophagy High 23235332
2012 MAPK14/p38α is required for irinotecan (SN-38) resistance in TP53-null colon cancer cells by inducing survival autophagy; constitutively active MAPK14/p38α decreases SN-38 sensitivity and induces autophagy, and inhibition of either MAPK14 or autophagy sensitizes cells to drug therapy in a mutually dependent manner. Overexpression of constitutively active MAPK14, siRNA knockdown, pharmacological inhibition, autophagy flux assays Autophagy Medium 22647487
2013 p38α autoactivation during myocardial ischemia occurs in cis by direct interaction with TAB1(371-416). Crystal structures revealed a bipartite docking site for TAB1 in the p38α C-terminal kinase lobe; TAB1 binding stabilizes active p38α and induces helical extension of the Thr-Gly-Tyr activation segment, allowing autophosphorylation in cis. TAT-TAB1(371-416) peptide rapidly activates p38 in cardiac myocytes and perfused hearts and causes profound functional perturbation. A chemical-genetic approach in bacterial and cell-free systems confirmed the cis autophosphorylation mechanism. X-ray crystallography, solution characterization, chemical-genetic approaches, coexpression in mammalian/bacterial/cell-free systems, isolated cardiomyocytes and perfused heart ex vivo Nature structural & molecular biology High 24037507
2013 p38α regulates cardiac contractility by suppressing phosphorylation of phospholamban (PLB) via activation of protein phosphatase 2A, which dephosphorylates PP1 inhibitor-1, thereby activating PP1 and reducing PLB phosphorylation. Inhibition of p38α (dominant-negative p38α or RNAi) specifically enhanced PLB phosphorylation and SERCA2a-dependent diastolic Ca2+ uptake; this effect was p38α-specific and not observed with dominant-negative p38β. Dominant-negative overexpression, RNAi knockdown, Ca2+-transient measurements, protein phosphatase activity assays in cardiomyocytes and perfused hearts Journal of molecular and cellular cardiology Medium 24361238
2013 PRMT1 directly interacts with p38α (co-immunoprecipitation) and methylates p38α in vitro. PRMT1 acts upstream of p38α to promote erythroid differentiation; PRMT1-stimulated differentiation was abolished in p38α-knockdown cells but not p38β-knockdown cells, and PRMT1 enhanced p38 MAPK activation. Co-immunoprecipitation, in vitro methylation assay, shRNA knockdown, erythroid differentiation assays PloS one Medium 23483889
2014 Docking interactions between active p38α and MK2's C-terminal domain allosterically enhance p38α's enzymatic activity toward MK2 by promoting ATP binding and phosphoacceptor accommodation, thus accelerating the phosphotransfer reaction. This was characterized by solution NMR showing that phosphorylation and ATP loading collaboratively induce active p38α conformation, and the docking interaction further enhances catalysis beyond just substrate anchoring. Solution NMR, in vitro kinase assay with dually phosphorylated p38α and MK2 fragments Nature structural & molecular biology High 25038803
2014 Chemical phosphorylation of p38α at Thr180 (using a phosphocysteine mimic, pCys180) is sufficient to switch the kinase to an active state capable of phosphorylating ATF2; phosphorylation at position 172 does not activate the kinase. This demonstrates Thr180 as the dominant activating site. Type II inhibitors inhibit phosphorylated p38α, whereas Type I inhibitors show differential behavior. Tag-and-modify chemical modification, in vitro kinase assay with ATF2 substrate, kinetic analysis Journal of the American Chemical Society High 24393126
2014 MAPK14/p38α modulates glucose metabolism during starvation at two levels: (1) it increases SLC2A3 (GLUT3) mRNA and protein by enhancing HIF1A protein stability, boosting glucose uptake; (2) it promotes metabolic shift from glycolysis to the pentose phosphate pathway by inducing proteasomal degradation of PFKFB3 via KEN box and DSG motif Ser273 recognition sequences. This MAPK14-driven metabolic reprogramming sustains NADPH production and reduces ROS, limiting autophagy. MAPK14 knockdown, pharmacological inhibition, metabolic flux assays, protein stability assays, mutagenesis of PFKFB3 degradation motifs Autophagy Medium 25046111
2014 p38α functions downstream of BMP2/7 signaling and MKK6 (but not MKK3) in ameloblasts to regulate amelogenin and β4-integrin expression and p21 expression in the enamel knot, required for tooth morphogenesis and enamel secretion. Conditional p38α knockout (K14-Cre), MKK3 and MKK6 knockout mice, BMP2/7 stimulation in explant culture and ameloblast cell line The Journal of biological chemistry High 25406311
2015 MAPK14/p38α is required for mitophagy induced by starvation or hypoxia in mammalian cells. Knockdown of MAPK14 severely suppressed mitophagy, which was found to occur predominantly through alternative autophagy (RAB9A/B-dependent) rather than conventional macroautophagy. pH-sensitive fluorescent protein Keima mitophagy assay, siRNA knockdown, Atg5 knockout MEFs Autophagy Medium 25831013
2015 Hepatic p38α negatively regulates AMPK signaling to maintain gluconeogenesis during fasting. Loss of hepatic p38α increases AMPKα phosphorylation without altering CREB phosphorylation; dominant-negative AMPKα abolished the anti-gluconeogenic effect of p38α loss. TAK1 knockdown decreased AMPKα phosphorylation in p38α-deficient cells, suggesting a negative feedback loop. Liver-specific p38α knockout mice, adenoviral dominant-negative constructs, pyruvate tolerance tests, in vivo and in vitro gluconeogenesis assays Journal of hepatology High 25595884
2015 Mitophagy-related pyridinyl-imidazole class inhibitors (SB203580/SB202190) interfere with autophagic flux in a MAPK14/p38-independent manner, making them unsuitable as pharmacological tools to study p38-dependent autophagy. Pharmacological inhibition with SB203580/SB202190 in p38-deficient cells, autophagic flux assays Autophagy Medium 26061537
2016 p38α activity is required for myogenesis by displacing the histone methyltransferase KMT1A from MyoD via direct phosphorylation of KMT1A; p38α activity removes repressive H3K9me3 marks from the Myogenin promoter and is necessary and sufficient for establishing active H3K9 acetylation at this locus. Pharmacological inhibition, lentiviral p38α shRNA, constitutively active upstream kinase overexpression, co-immunoprecipitation, ChIP for H3K9me3 and H3K9ac, in vitro kinase assay Skeletal muscle High 27551368
2017 Sustained p38α activation drives metabolic changes including increased glucose and glutamine dependence, enhanced respiration, and elevated mitochondrial ROS, partly through the downstream kinase MK2 (MAPKAPK2). Elevated mitochondrial superoxide from this metabolic state contributes to p38α-induced reduced cell survival. Inducible p38α activation system, metabolic flux assays, MK2 knockout/knockdown, ROS measurement Scientific reports Medium 28900160
2018 Crystal structure of active pp38α in complex with TAB1 (residues 1-438) in the active state was solved. Four TAB1 residues required for docking onto p38α were identified; knock-in mice with substitutions at these four TAB1 residues were viable and showed reduced infarction volume and disabled TAB1 transphosphorylation following myocardial ischemia, while myocardial p38α activation was only mildly attenuated. X-ray crystallography, TAB1 knock-in mouse model, in vivo regional myocardial ischemia model, fragment-based small molecule screening for disruption of p38α-TAB1 interaction JCI insight High 30135318
2018 TAB1-induced p38α autoactivation in cis requires an intramolecular hydrogen bond between Thr185 and Asp150 in the activation segment. Mutation T185G disrupts this hydrogen bond and specifically disables autophosphorylation while leaving MKK3/MKK6-mediated activation and downstream substrate phosphorylation intact. Cardiac cells expressing p38α(T185G) are resistant to ischemic injury. Structural analysis of p38α-TAB1 crystal structure, T185G mutagenesis, in vitro and in vivo kinase assays, TAB1-binding assay, cardiac myocyte injury model Molecular and cellular biology High 29229647
2018 p38α phosphorylates CtIP (DNA repair regulator), and loss of p38α signaling in breast cancer cells impairs ATR activation and homologous recombination repair, increasing replication stress, DNA damage, and chromosome instability. Pharmacological p38α inhibition potentiates taxane effects by boosting chromosome instability. Conditional p38α knockout/pharmacological inhibition, DNA damage assays, HR repair assays, ATR activation assays, murine models and patient-derived xenografts Cancer cell Medium 29805078
2018 In dendritic cells, p38α negatively regulates IL-27 production through the TAK1-MKK4/7-JNK-c-Jun axis; loss of p38α in colonic cDC1s leads to hyperactivation of JNK-c-Jun, elevated IL-27, and increased Tr1 cell differentiation. ChIP assay confirmed direct binding of c-Jun to the Il27p28 promoter, which was enhanced in p38α-deficient DCs. DC-specific p38α conditional knockout, ChIP assay, JNK pathway inhibition, cytokine measurement Proceedings of the National Academy of Sciences of the United States of America High 30541887
2019 p38α in mesenchymal stem/stromal cells negatively regulates an angiogenic program including TGF-β-induced acquisition of an endothelial phenotype (mesenchymal-to-endothelial transition) and JNK-dependent signaling. Abrogation of p38α in mesenchymal cells increases tumorigenesis correlated with enhanced angiogenesis. Genetic mouse models with mesenchymal-specific p38α deletion, in vivo tumor models, genetic epistasis with TGF-β and JNK pathways Nature communications High 31296856
2019 Sustained p38α activation drives autophagosome formation and enhances autophagic flux, requiring both increased mitochondrial ROS and p38α-mediated phosphorylation of ULK1 at Ser-555. This autophagy induction directs cancer cells preferentially toward senescence rather than apoptosis, protecting them from chemotherapy-induced apoptosis. Inducible p38α activation system, autophagy flux assays, ULK1 phosphorylation assays, genetic knockdown, cell fate analysis Cell death & disease Medium 31092814
2019 Macrophage p38α promotes steatohepatitis by inducing M1 macrophage polarization and pro-inflammatory cytokine secretion (CXCL2, IL-1β, CXCL10, IL-6). In co-culture, p38α-deleted macrophages attenuated steatohepatitic changes in hepatocytes via decreased secretion of TNF-α, CXCL10, and IL-6; restoration of these cytokines rescued the phenotype. Macrophage-specific p38α conditional knockout, co-culture experiments, cytokine restoration experiments, macrophage polarization assays Journal of hepatology High 30914267
2019 Myeloid p38α drives intestinal IGF-1 production in macrophages, which mediates colon inflammation and tumorigenesis. Genetic and pharmacological inhibition of p38α in myeloid cells reduced IGF-1 production and tumorigenesis; IGF-1 signaling acted downstream of p38α in macrophages. Myeloid-specific p38α conditional knockout, pharmacological inhibition, adenoviral overexpression/knockdown of IGF-1 EMBO molecular medicine Medium 29907597
2019 In vascular smooth muscle cells, MAPK14 suppresses the contractile phenotype and promotes proliferation and inflammation via a p65/NF-κB-dependent pathway. NOX4 contributes upstream to MAPK14-mediated suppression of VSMC contractile differentiation. Inducible SMC-specific MAPK14 knockout mice showed reduced neointima formation after carotid injury. Inducible SMC-specific knockout mice, carotid ligation injury model, VSMC lineage tracing, RNA array, pharmacological inhibition, MAPK14 forced expression Redox biology High 30771750
2019 p38α in lung cancer epithelial cells promotes KRAS(G12V)-driven tumor progression via autonomous expression of TIMP-1, which stimulates cell proliferation in an autocrine manner. Despite acting as a tumor suppressor in healthy alveolar progenitor cells, p38α is required for proliferation and malignization of lung cancer cells. Conditional p38α deletion in vivo, KRAS(G12V) lung cancer mouse models, pharmacological inhibition, TIMP-1 expression/secretion assays Proceedings of the National Academy of Sciences of the United States of America Medium 31969449
2020 Activation of p38α in lung fibroblasts by tumor-derived factors leads to inactivation of type I interferon signaling and stimulation of fibroblast activation protein (FAP) expression. FAP drives extracellular matrix remodeling and chemokine expression enabling neutrophil lung infiltration, establishing a pre-metastatic niche for pulmonary metastases. p38α activation in lung fibroblasts by tumor-conditioned medium, FAP gain/loss-of-function, in vivo metastasis models, pharmacological p38 inhibition Nature cancer Medium 34124690
2021 Constitutive activation of p38α in the liver (via intrinsically active p38α allele) is sufficient to cause macrovesicular fatty liver, associated with upregulation of MUC13, CIDEA, PPARγ, ATF3, and c-jun mRNAs. This fatty liver phenotype was reversible upon shutting off p38α mutant expression. Transgenic inducible liver-specific expression of active p38α allele, histology, gene expression analysis, reversibility experiment Proceedings of the National Academy of Sciences of the United States of America Medium 33811139
2021 SUMOylation of MAPK14/p38α occurs at lysine 152. p38α-SUMOylation acts as a sensor/accelerator of ROS generation through interaction with and activation of MK2 in the nucleus; ROS accumulation in turn promotes p38α SUMOylation by stabilizing PIASxα. This PIASxα/p38α-SUMOylation/MK2 cis-axis facilitates gastric cancer metastasis. Immunoprecipitation, pull-down assays, SUMOylation site mapping, nuclear localization studies, ROS assays Cell death & disease Medium 34686655
2022 p38α in B cells drives plasma cell differentiation by upregulating BLIMP1 transcription through downstream effectors TCF3, TCF4, and IRF4 (identified by CRISPR/Cas9 screening). B cell-specific p38α deletion severely impaired plasma cell differentiation and antibody responses while sparing B cell development and germinal center responses. B cell-specific conditional p38α knockout, Blimp1 reporter mouse, CRISPR/Cas9 screen, antibody response assays Nature communications High 36443297
2022 P38α in uterine stroma phosphorylates the E3 ubiquitin ligase Ube3c at serine741, restraining Ube3c's polyubiquitination activity toward progesterone receptor (PR) and preventing its proteasomal degradation. In uterine-specific p38α knockout mice, Ube3c targets PR for degradation, causing defective implantation and female infertility. Uterine-specific p38α conditional knockout, in vitro phosphorylation assay (LC-MS confirmed Ube3c-S741 phosphorylation), ubiquitination assays, proteasome inhibitor rescue, Foxo1S273D/A knockin models Proceedings of the National Academy of Sciences of the United States of America High 35914132
2022 p38α in cDC1 dendritic cells regulates Th2-cell differentiation by modulating the MK2-c-FOS-IL-12 axis. cDC1-specific but not cDC2-specific p38α deletion promoted Th2 responses, and the mechanism involved p38α-dependent MK2 activation controlling c-FOS and IL-12 production. Cell-type-specific conditional knockouts (cDC1, cDC2, macrophage), MK2-c-FOS-IL-12 pathway analysis, Th2 differentiation assays Cellular & molecular immunology Medium 35551270
2023 Cryo-EM structure of p38α in complex with its MAP2K MKK6 reveals a dynamic, multistep dual phosphorylation mechanism for p38α activation. The MAP2K-disordered N-terminal amino termini determine pathway specificity. Catalytically relevant interactions between MKK6 and p38α were identified and validated by HDX-MS, molecular dynamics simulations, and cell-based experiments. Cryo-electron microscopy, hydrogen-deuterium exchange mass spectrometry, molecular dynamics simulations, cell-based functional experiments Science (New York, N.Y.) High 37708276
2023 Hepatic p38α phosphorylates FOXO1 at S273 in response to glucagon (via EPAC2 signaling), increasing FOXO1 protein stability and promoting hepatic glucose production. This EPAC2-p38α-pFOXO1-S273 axis is required for glucagon-stimulated HGP; Foxo1S273A knock-in mice showed reduced glucose production and improved insulin sensitivity. siRNA knockdown, adeno-associated virus shRNA in liver-specific knockout mice, in vitro LC-MS phosphorylation assay, Foxo1S273D and Foxo1S273A knockin mice, glucagon tolerance tests Diabetologia High 37202506
2024 MAPK phosphatase 1 (MKP1) promotes lung myofibroblast dedifferentiation and restores apoptosis sensitivity by dephosphorylating p38α MAPK. Fibroblast-specific MKP1 deletion after peak bleomycin-induced fibrosis abrogated spontaneous fibrosis resolution; treatment with p38α inhibitor VX-702 restored resolution in MKP1-knockout transgenic mice. Fibroblast-specific conditional MKP1 knockout (gain- and loss-of-function), bleomycin fibrosis model, pharmacological p38α inhibition with VX-702, MKP1-p38α dephosphorylation assays The Journal of clinical investigation High 38512415
2025 Lobeline binds directly to MAPK14 (confirmed by DARTS assay and target-responsive accessibility profiling), preventing nuclear translocation of MAPK14. This reduces phosphorylation of p53, relieving p53-mediated transcriptional repression of SLURP1, which in turn promotes M1 macrophage polarization of tumor-associated macrophages and suppresses colorectal cancer growth. Target-responsive accessibility profiling, DARTS assay, nuclear/cytoplasmic fractionation, p53 phosphorylation assays, Slurp1-deficient MC38 xenografts Advanced science (Weinheim, Baden-Wurttemberg, Germany) Medium 39840525

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2007 p38alpha suppresses normal and cancer cell proliferation by antagonizing the JNK-c-Jun pathway. Nature genetics 306 17468757
2007 p38alpha MAP kinase is essential in lung stem and progenitor cell proliferation and differentiation. Nature genetics 254 17468755
2003 Feedback control of the protein kinase TAK1 by SAPK2a/p38alpha. The EMBO journal 246 14592977
2005 MAP kinase p38 inhibitors: clinical results and an intimate look at their interactions with p38alpha protein. Current medicinal chemistry 191 16378500
2014 p38α MAPK pathway: a key factor in colorectal cancer therapy and chemoresistance. World journal of gastroenterology 189 25110412
2015 Mitophagy is primarily due to alternative autophagy and requires the MAPK1 and MAPK14 signaling pathways. Autophagy 177 25831013
2019 Macrophage p38α promotes nutritional steatohepatitis through M1 polarization. Journal of hepatology 176 30914267
2004 The role of p38alpha mitogen-activated protein kinase activation in renal fibrosis. Journal of the American Society of Nephrology : JASN 168 14747383
2007 p38alpha: a suppressor of cell proliferation and tumorigenesis. Cell cycle (Georgetown, Tex.) 163 17957136
2015 The Stress Kinase p38α as a Target for Cancer Therapy. Cancer research 157 26377941
2004 Inhaled p38alpha mitogen-activated protein kinase antisense oligonucleotide attenuates asthma in mice. American journal of respiratory and critical care medicine 143 15557129
1995 Mxi2, a mitogen-activated protein kinase that recognizes and phosphorylates Max protein. Proceedings of the National Academy of Sciences of the United States of America 133 7479834
2015 Roles of p38α mitogen-activated protein kinase in mouse models of inflammatory diseases and cancer. The FEBS journal 128 25728574
2019 Regulation of tumor angiogenesis and mesenchymal-endothelial transition by p38α through TGF-β and JNK signaling. Nature communications 112 31296856
2006 CXCL12 and C5a trigger cell migration via a PAK1/2-p38alpha MAPK-MAPKAP-K2-HSP27 pathway. Cellular signalling 103 16574378
2009 The p38alpha kinase plays a central role in inflammation. Current topics in medicinal chemistry 96 19747121
2021 Current status and future prospects of p38α/MAPK14 kinase and its inhibitors. European journal of medicinal chemistry 93 33524689
2013 Mechanism and consequence of the autoactivation of p38α mitogen-activated protein kinase promoted by TAB1. Nature structural & molecular biology 91 24037507
2018 Targeting p38α Increases DNA Damage, Chromosome Instability, and the Anti-tumoral Response to Taxanes in Breast Cancer Cells. Cancer cell 80 29805078
2012 MAPK14/p38α confers irinotecan resistance to TP53-defective cells by inducing survival autophagy. Autophagy 78 22647487
2006 Multiple activation mechanisms of p38alpha mitogen-activated protein kinase. The Journal of biological chemistry 77 16849316
2007 Genetic deficiency of p38alpha reveals its critical role in myoblast cell cycle exit: the p38alpha-JNK connection. Cell cycle (Georgetown, Tex.) 72 17534150
2019 Autophagy-induced senescence is regulated by p38α signaling. Cell death & disease 70 31092814
2004 Active mutants of the human p38alpha mitogen-activated protein kinase. The Journal of biological chemistry 70 15284239
2012 Comparative expression profiling identifies differential roles for Myogenin and p38α MAPK signaling in myogenesis. Journal of molecular cell biology 67 22847234
2014 MAPK14/p38α-dependent modulation of glucose metabolism affects ROS levels and autophagy during starvation. Autophagy 64 25046111
2000 Constitutive activity and differential localization of p38alpha and p38beta MAPKs in adult mouse brain. Journal of neuroscience research 61 10820433
2014 p38α (MAPK14) critically regulates the immunological response and the production of specific cytokines and chemokines in astrocytes. Scientific reports 60 25502009
2020 Activation of p38α stress-activated protein kinase drives the formation of the pre-metastatic niche in the lungs. Nature cancer 57 34124690
2019 Vascular smooth muscle-MAPK14 is required for neointimal hyperplasia by suppressing VSMC differentiation and inducing proliferation and inflammation. Redox biology 52 30771750
2018 Protein kinase p38α signaling in dendritic cells regulates colon inflammation and tumorigenesis. Proceedings of the National Academy of Sciences of the United States of America 42 30541887
2003 p38alpha isoform Mxi2 binds to extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase and regulates its nuclear activity by sustaining its phosphorylation levels. Molecular and cellular biology 42 12697810
2016 Targeting neuronal MAPK14/p38α activity to modulate autophagy in the Alzheimer disease brain. Autophagy 39 27715387
2014 Allosteric enhancement of MAP kinase p38α's activity and substrate selectivity by docking interactions. Nature structural & molecular biology 39 25038803
2014 Synthetic phosphorylation of p38α recapitulates protein kinase activity. Journal of the American Chemical Society 38 24393126
2018 Targeted ablation of p38α MAPK suppresses denervation-induced muscle atrophy. Scientific reports 37 29899565
2015 Hepatic p38α regulates gluconeogenesis by suppressing AMPK. Journal of hepatology 37 25595884
2009 p38alpha MAP kinase C-terminal domain binding pocket characterized by crystallographic and computational analyses. Journal of molecular biology 37 19501598
2004 Improved expression, purification, and crystallization of p38alpha MAP kinase. Protein expression and purification 37 15294293
2020 p38α Regulates Expression of DUX4 in a Model of Facioscapulohumeral Muscular Dystrophy. The Journal of pharmacology and experimental therapeutics 35 32576599
2020 P38α MAPK Signaling-A Robust Therapeutic Target for Rab5-Mediated Neurodegenerative Disease. International journal of molecular sciences 35 32751991
2018 The p38α Stress Kinase Suppresses Aneuploidy Tolerance by Inhibiting Hif-1α. Cell reports 34 30332653
2015 Gene structure, molecular characterization and transcriptional expression of two p38 isoforms (MAPK11 and MAPK14) from rock bream (Oplegnathus fasciatus). Fish & shellfish immunology 34 26363230
2010 p38alpha is required for ovarian cancer cell metabolism and survival. International journal of gynecological cancer : official journal of the International Gynecological Cancer Society 34 20169663
2006 Involvement of p38alpha mitogen-activated protein kinase in lung metastasis of tumor cells. The Journal of biological chemistry 34 17028194
2023 Architecture of the MKK6-p38α complex defines the basis of MAPK specificity and activation. Science (New York, N.Y.) 33 37708276
2022 The kinase p38α functions in dendritic cells to regulate Th2-cell differentiation and allergic inflammation. Cellular & molecular immunology 33 35551270
2012 Mechanism for p38α-mediated experimental autoimmune encephalomyelitis. The Journal of biological chemistry 32 22637476
2023 Inhibition of p38α MAPK restores neuronal p38γ MAPK and ameliorates synaptic degeneration in a mouse model of DLB/PD. Science translational medicine 31 37163617
2014 p38α MAPK is required for tooth morphogenesis and enamel secretion. The Journal of biological chemistry 31 25406311
2024 MAPK phosphatase 1 inhibition of p38α within lung myofibroblasts is essential for spontaneous fibrosis resolution. The Journal of clinical investigation 30 38512415
2020 MAPK14 (p38α) inhibition effects against metastatic gastric cancer cells: A potential biomarker and pharmacological target. Toxicology in vitro : an international journal published in association with BIBRA 27 32243890
2020 In silico molecular target prediction unveils mebendazole as a potent MAPK14 inhibitor. Molecular oncology 27 33021050
2021 Circular RNA circACSL1 aggravated myocardial inflammation and myocardial injury by sponging miR-8055 and regulating MAPK14 expression. Cell death & disease 26 33986259
2018 Myeloid p38α signaling promotes intestinal IGF-1 production and inflammation-associated tumorigenesis. EMBO molecular medicine 26 29907597
2016 Selective p38α MAP kinase/MAPK14 inhibition in enzymatically modified LDL-stimulated human monocytes: implications for atherosclerosis. FASEB journal : official publication of the Federation of American Societies for Experimental Biology 26 27871059
2015 The problem of pyridinyl imidazole class inhibitors of MAPK14/p38α and MAPK11/p38β in autophagy research. Autophagy 26 26061537
2012 MAPK14 and CNR1 gene variant interactions: effects on brain volume deficits in schizophrenia patients with marijuana misuse. Psychological medicine 26 22850347
2022 Shikonin triggers GSDME-mediated pyroptosis in tumours by regulating autophagy via the ROS-MAPK14/p38α axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 25 36610142
2020 In silico identification of MAPK14-related lncRNAs and assessment of their expression in breast cancer samples. Scientific reports 25 32433496
2017 Induction of oxidative metabolism by the p38α/MK2 pathway. Scientific reports 25 28900160
2015 The p38α mitogen-activated protein kinase is a key regulator of myelination and remyelination in the CNS. Cell death & disease 25 25950478
2014 p38α mitogen-activated kinase mediates cardiomyocyte apoptosis induced by palmitate. Biochemical and biophysical research communications 24 24931668
2012 Inhibition of autophagy through MAPK14-mediated phosphorylation of ATG5. Autophagy 24 23235332
2009 Mitogen-activated protein kinase p38alpha and retinal ischemic preconditioning. Experimental eye research 24 19631642
2000 Mxi2, a splice variant of p38 stress-activated kinase, is a distal nephron protein regulated with kidney ischemia. American journal of physiology. Cell physiology 24 10751326
2025 Targeting MAPK14 by Lobeline Upregulates Slurp1-Mediated Inhibition of Alternative Activation of TAM and Retards Colorectal Cancer Growth. Advanced science (Weinheim, Baden-Wurttemberg, Germany) 23 39840525
2018 HOXA5 overexpression promotes osteosarcoma cell apoptosis through the p53 and p38α MAPK pathway. Gene 23 30521886
2013 Recent developments of p38α MAP kinase inhibitors as antiinflammatory agents based on the imidazole scaffolds. Current medicinal chemistry 23 23317165
2011 p38α and p38β mitogen-activated protein kinases determine cholinergic transdifferentiation of sympathetic neurons. The Journal of neuroscience : the official journal of the Society for Neuroscience 23 21865449
2020 Requirement for epithelial p38α in KRAS-driven lung tumor progression. Proceedings of the National Academy of Sciences of the United States of America 22 31969449
2019 Knockdown of MAPK14 inhibits the proliferation and migration of clear cell renal cell carcinoma by downregulating the expression of CDC25B. Cancer medicine 22 31856414
2013 p38α regulates SERCA2a function. Journal of molecular and cellular cardiology 22 24361238
2000 Distinct carboxy-termini confer divergent characteristics to the mitogen-activated protein kinase p38alpha and its splice isoform Mxi2. FEBS letters 22 10838079
2022 Role of GDF15/MAPK14 Axis in Chondrocyte Senescence as a Novel Senomorphic Agent in Osteoarthritis. International journal of molecular sciences 21 35806043
2020 Mapping p38α mitogen-activated protein kinase signaling by proximity-dependent labeling. Protein science : a publication of the Protein Society 21 32189389
2020 Design, synthesis and anti-inflammatory activity of imidazol-5-yl pyridine derivatives as p38α/MAPK14 inhibitor. Bioorganic & medicinal chemistry 21 33422910
2018 The TAB1-p38α complex aggravates myocardial injury and can be targeted by small molecules. JCI insight 21 30135318
2024 RvD1 improves resident alveolar macrophage self-renewal via the ALX/MAPK14/S100A8/A9 pathway in acute respiratory distress syndrome. Journal of advanced research 20 38237770
2021 Active p38α causes macrovesicular fatty liver in mice. Proceedings of the National Academy of Sciences of the United States of America 20 33811139
2021 LncRNA XIST knockdown alleviates LPS-induced acute lung injury by inactivation of XIST/miR-132-3p/MAPK14 pathway : XIST promotes ALI via miR-132-3p/MAPK14 axis. Molecular and cellular biochemistry 20 34346000
2019 p38α Mitogen-Activated Protein Kinase Is a Druggable Target in Pancreatic Adenocarcinoma. Frontiers in oncology 20 31828036
2018 TAB1-Induced Autoactivation of p38α Mitogen-Activated Protein Kinase Is Crucially Dependent on Threonine 185. Molecular and cellular biology 20 29229647
2019 p38α MAPK proximity assay reveals a regulatory mechanism of alternative splicing in cardiomyocytes. Biochimica et biophysica acta. Molecular cell research 19 31505169
2015 A Comprehensive Structural Overview of p38α MAPK in Complex with Type I Inhibitors. ChemMedChem 19 26012502
2013 Protein arginine methyltransferase 1 interacts with and activates p38α to facilitate erythroid differentiation. PloS one 19 23483889
2008 A role for p38alpha mitogen-activated protein kinase in embryonic cardiac differentiation. FEBS letters 19 18314011
2023 Narirutin ameliorates alcohol-induced liver injury by targeting MAPK14 in zebrafish larvae. Biomedicine & pharmacotherapy = Biomedecine & pharmacotherapie 18 37633055
2022 P38α MAPK is a gatekeeper of uterine progesterone responsiveness at peri-implantation via Ube3c-mediated PGR degradation. Proceedings of the National Academy of Sciences of the United States of America 18 35914132
2022 Androgen receptor suppresses inflammatory response of airway epithelial cells in allergic asthma through MAPK1 and MAPK14. Human & experimental toxicology 18 35982617
2019 Neuronal p38α mediates age-associated neural stem cell exhaustion and cognitive decline. Aging cell 17 31560167
2016 p38α MAPK disables KMT1A-mediated repression of myogenic differentiation program. Skeletal muscle 17 27551368
2007 Involvement of p38alpha in kainate-induced seizure and neuronal cell damage. Journal of receptor and signal transduction research 17 17613723
2023 Hepatic p38α MAPK controls gluconeogenesis via FOXO1 phosphorylation at S273 during glucagon signalling in mice. Diabetologia 16 37202506
2017 p38α regulates actin cytoskeleton and cytokinesis in hepatocytes during development and aging. PloS one 16 28166285
2021 Positive feedback between ROS and cis-axis of PIASxα/p38α-SUMOylation/MK2 facilitates gastric cancer metastasis. Cell death & disease 15 34686655
2022 A p38α-BLIMP1 signalling pathway is essential for plasma cell differentiation. Nature communications 14 36443297
2021 Overexpression of miRNA-22-3p attenuates osteoporosis by targeting MAPK14. Experimental and therapeutic medicine 14 33986857
2019 Activator protein-1 and caspase 8 mediate p38α MAPK-dependent cardiomyocyte apoptosis induced by palmitic acid. Apoptosis : an international journal on programmed cell death 13 30879166
2017 p38α regulates cytokine-induced IFNγ secretion via the Mnk1/eIF4E pathway in Th1 cells. Immunology and cell biology 13 28611474

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