Affinage

MAPK14

Mitogen-activated protein kinase 14 · UniProt Q16539

Round 2 corrected
Length
360 aa
Mass
41.3 kDa
Annotated
2026-04-28
130 papers in source corpus 61 papers cited in narrative 61 extracted findings

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAPK14 (p38α) is a stress-activated serine/threonine MAP kinase that transduces inflammatory, osmotic, and genotoxic signals into transcriptional, metabolic, and cell-fate decisions across virtually all mammalian cell types (PMID:7914033, PMID:7997261). Activated by dual phosphorylation on Thr180/Tyr182 via upstream kinases MKK3, MKK4, and MKK6, or through TAB1-mediated cis-autoactivation that depends on an intramolecular Thr185–Asp150 hydrogen bond, p38α phosphorylates a broad substrate repertoire—including transcription factors (ATF2, MEF2C, CHOP), downstream kinases (MK2/MAPKAPK2, MSK1), and autophagy regulators (ATG5, ULK1)—and is inactivated by MKP1-mediated dephosphorylation (PMID:7535770, PMID:7839144, PMID:29229647, PMID:38512415, PMID:14592977). Allosteric docking of substrates such as MK2 enhances active-site catalysis, and the kinase follows an ordered sequential mechanism in which protein substrate binds before ATP (PMID:25038803, PMID:9265622). Cell-type–specific functions include programming TH17 immunity in dendritic cells, driving pro-inflammatory cytokine production in macrophages, promoting myoblast differentiation and fusion, mediating ischemic cardiomyocyte injury via TAB1-autoactivation, and regulating neuronal survival during aging and excitotoxicity (PMID:22231518, PMID:30914267, PMID:17534150, PMID:30135318, PMID:31560167).

Mechanistic history

Synthesis pass · year-by-year structured walk · 15 steps
  1. 1994 High

    Identification of MAPK14/p38 as a novel stress-responsive MAP kinase and as the molecular target of pyridinyl-imidazole anti-inflammatory drugs established a new signaling axis linking environmental stress to inflammatory cytokine production.

    Evidence Molecular cloning and phosphorylation studies in LPS/osmotic-stress-stimulated cells; photoaffinity labeling identified p38 as the CSBP target correlating with IL-1/TNF inhibition

    PMID:7914033 PMID:7997261

    Open questions at the time
    • Upstream activating kinases unknown at this stage
    • In vivo physiological roles not yet defined
    • Substrate specificity not yet characterized
  2. 1995 High

    Defining the dual Thr180/Tyr182 phosphorylation requirement and cloning of upstream kinases MKK3 and MKK4 placed p38 within a three-tiered MAP kinase cascade distinct from the ERK pathway.

    Evidence Phosphorylation site mapping by mutagenesis; reconstitution of MKK3/MKK4→p38 cascades in vitro and in cells

    PMID:7535770 PMID:7716521 PMID:7839144

    Open questions at the time
    • MKK6 not yet identified as a selective activator
    • Mechanism of stimulus-specific pathway selection unclear
  3. 1996 High

    Identification of transcription factors ATF2, Elk-1, and CHOP as direct p38 substrates revealed that nuclear gene regulation is a primary output of the pathway, linking stress signaling to transcriptional reprogramming.

    Evidence Reporter assays showing MKK3/6→p38→ATF2/Elk-1 activation; in vitro phosphorylation of CHOP Ser78/81 with SB203580-sensitive in vivo validation

    PMID:8622669 PMID:8650547

    Open questions at the time
    • Full substrate repertoire unknown
    • Mechanism of substrate selectivity not resolved
  4. 1997 High

    Biochemical studies defined an ordered sequential kinetic mechanism (protein substrate binds before ATP) and identified MEF2C and MSK1 as additional substrates/effectors, expanding the downstream signaling network.

    Evidence Steady-state kinetics with dead-end inhibitor analysis; MEF2C phosphorylation in LPS-stimulated monocytes; MSK1 activation and CREB phosphorylation in stress-stimulated cells

    PMID:9069290 PMID:9265622 PMID:9687510

    Open questions at the time
    • Structural basis for ordered mechanism not determined
    • Relative contributions of MSK1 versus direct substrates to gene expression unknown
  5. 2000 High

    Genetic ablation in mice demonstrated that p38α is essential for placental angiogenesis and embryonic viability, and also functions as a negative regulator of Ras-driven proliferation by antagonizing the JNK/c-Jun pathway.

    Evidence p38α knockout mice showing embryonic lethality with placental labyrinth loss; proliferation and JNK epistasis assays in p38α-deficient cells

    PMID:10973481 PMID:10978313

    Open questions at the time
    • Placental substrates mediating angiogenesis not identified
    • Cell-type-specific contributions in vivo not yet dissected
  6. 2002 High

    Crystal structures of p38α with allosteric (DFG-out) and ATP-competitive inhibitors revealed distinct druggable conformations and the role of Gly110 in isoform-selective inhibitor binding.

    Evidence X-ray crystallography of BIRB 796 and quinazolinone complexes; mutagenesis of Gly110 confirming selectivity determinant

    PMID:11896401 PMID:12897767

    Open questions at the time
    • Structures of p38α in complex with physiological substrates lacking
    • DFG-out mechanism not linked to in vivo activation dynamics
  7. 2003 High

    Discovery that p38α phosphorylates TAB1 to create a negative feedback loop limiting TAK1 activity, and that p38α mediates type I interferon transcriptional responses, established dual roles in signal termination and innate immunity.

    Evidence TAB1 phosphosite identification by mass spectrometry with enhanced TAK1 activity in p38α-null MEFs; IFN-dependent reporter and antiviral assays in p38α knockout fibroblasts

    PMID:14578350 PMID:14592977

    Open questions at the time
    • Stoichiometry and timing of TAB1 feedback in vivo unresolved
    • Relative contributions of MK2 vs MSK1 to IFN response unclear
  8. 2006 High

    Multiple MKK-independent activation routes were delineated—TAB1-mediated autoactivation and peroxynitrite-induced disulfide-dependent activation—demonstrating that p38α integrates mechanistically distinct upstream signals.

    Evidence MKK3/4/6/7 double-knockout MEFs retaining partial p38α activation; cysteine mutagenesis blocking peroxynitrite-dependent phosphorylation

    PMID:16849316

    Open questions at the time
    • Relative contribution of each activation mode in specific pathological contexts not quantified
    • Structural basis of disulfide-mediated activation unknown
  9. 2007 High

    Cell-type-specific roles were established in myoblast differentiation (p38α required for cell cycle exit) and neuronal excitotoxicity (RhoA–p38α axis drives calcium-induced neuronal death), demonstrating context-dependent pro-survival versus pro-death functions.

    Evidence p38α knockout myoblasts failing to exit cell cycle due to JNK hyperactivation; RhoA gain/loss-of-function in primary neurons with p38α activation and Bcl-2 rescue

    PMID:17369826 PMID:17534150

    Open questions at the time
    • Direct substrates mediating cell cycle exit in myoblasts not identified
    • How RhoA mechanistically activates p38α remains unclear
  10. 2011 High

    Dendritic cell-specific p38α was shown to program TH17 immunity, and p38α was found to promote anoikis in mammary morphogenesis via ATF-2-dependent BimEL transcription, revealing tissue-specific immune and tumor-suppressive roles.

    Evidence DC-specific p38α knockout protecting from EAE; 3D mammary culture and MKK3/6 knockout mice showing luminal filling from impaired anoikis

    PMID:21610252 PMID:22231518

    Open questions at the time
    • Direct p38α substrates in DCs controlling TH17 cytokine program not fully mapped
    • Whether anoikis role extends beyond mammary tissue unknown
  11. 2012 High

    Direct phosphorylation of ATG5 at Thr75 by p38α established the kinase as a negative regulator of autophagosome–lysosome fusion, connecting stress MAPK signaling to autophagy control.

    Evidence In vitro kinase assays, phospho-mimetic ATG5 reconstitution in ATG5-null cells, autophagic flux measurement

    PMID:23235332

    Open questions at the time
    • Whether ATG5 Thr75 phosphorylation occurs under all p38α-activating stresses not tested
    • Contribution relative to ULK1 phosphorylation not parsed
  12. 2014 High

    NMR studies showed that substrate docking (MK2 C-terminal domain) allosterically enhances ATP and phosphoacceptor binding, revealing a feed-forward catalytic mechanism; separately, p38α was linked to metabolic reprogramming through PFKFB3 degradation and pentose phosphate pathway activation.

    Evidence Solution NMR of p38α–MK2 with kinetic validation; siRNA/mutant reconstitution defining PFKFB3 degradation motifs and metabolic flux

    PMID:25038803 PMID:25046111

    Open questions at the time
    • Whether allosteric enhancement applies to all docking substrates untested
    • In vivo metabolic rewiring by p38α in intact tissues not confirmed
  13. 2018 High

    Structural and genetic dissection of TAB1-mediated autoactivation showed that Thr185 forms an intramolecular hydrogen bond essential for autoactivation but dispensable for MKK-dependent activation; disrupting this interaction protected cardiomyocytes from ischemic injury in vivo.

    Evidence Crystal structure of p38α–TAB1 complex; T185G knock-in and TAB1 docking-deficient knock-in mice in ischemia models

    PMID:29229647 PMID:30135318

    Open questions at the time
    • Whether TAB1-autoactivation contributes to non-cardiac pathologies unknown
    • Therapeutic window for disrupting p38α–TAB1 interaction not defined
  14. 2019 High

    p38α was shown to phosphorylate ULK1 on Ser555, directly linking sustained p38α activity to autophagy induction and senescence-versus-apoptosis cell fate decisions; cell-type-specific knockouts in macrophages and neurons further defined roles in steatohepatitis, colitis-associated tumorigenesis, and age-related neurodegeneration.

    Evidence Inducible p38α system with ULK1 phosphorylation and autophagic flux; macrophage- and neuron-specific knockouts with inflammatory and cognitive phenotypes

    PMID:29907597 PMID:30914267 PMID:31092814 PMID:31560167

    Open questions at the time
    • Ser555 phosphorylation by p38α versus AMPK not kinetically distinguished
    • Interaction between autophagy and metabolic reprogramming arms not integrated
  15. 2024 High

    MKP1-mediated dephosphorylation of p38α was shown to drive myofibroblast dedifferentiation and fibrosis resolution, positioning p38α inactivation as the effector mechanism of physiological tissue repair.

    Evidence Fibroblast-specific MKP1 conditional knockout abrogating fibrosis resolution; rescue by p38α inhibitor VX-702 in bleomycin model

    PMID:38512415

    Open questions at the time
    • Whether other MAPK phosphatases contribute to p38α inactivation in fibrosis not tested
    • Applicability beyond pulmonary fibrosis not established

Open questions

Synthesis pass · forward-looking unresolved questions
  • Key unresolved questions include the structural basis of isoform-specific functions versus redundancy between p38α and p38β, the full inventory of direct p38α substrates in each cell type, and whether pathway-selective inhibition (e.g., TAB1-interaction disruptors) can achieve therapeutic benefit without the toxicity seen with catalytic-site p38 inhibitors.
  • No comprehensive phosphoproteomics of endogenous p38α substrates across cell types
  • No clinical validation of interaction-selective p38α modulators
  • Relative contribution of kinase-dependent versus scaffold functions of p38α unknown

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 16 GO:0016740 transferase activity 9
Localization
GO:0005634 nucleus 5 GO:0005829 cytosol 2 GO:0005886 plasma membrane 1
Pathway
R-HSA-162582 Signal Transduction 13 R-HSA-1266738 Developmental Biology 7 R-HSA-168256 Immune System 6 R-HSA-1640170 Cell Cycle 5 R-HSA-9612973 Autophagy 5 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-5357801 Programmed Cell Death 3
Partners
ATF2MAP2K3MAP2K4MAP2K6MAPKAPK2RPS6KA5TAB1ULK1

Evidence

Reading pass · 61 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1994 p38 (MAPK14) was identified as a protein kinase that is tyrosine phosphorylated in response to LPS and hyperosmolarity, and shares sequence similarity with the yeast HOG1 MAP kinase, establishing it as a stress-responsive MAP kinase. Molecular cloning, kinase assays, phosphorylation studies Science High 7914033
1994 MAPK14/p38 was identified as the target of pyridinyl-imidazole anti-inflammatory compounds (CSBPs); binding of these compounds inhibited p38 kinase activity and correlated with inhibition of IL-1 and TNF cytokine production from human monocytes. Radiolabeled/photoaffinity labeling, kinase activity assays Nature High 7997261
1995 p38 MAPK is activated by dual phosphorylation on Thr-180 and Tyr-182 in response to pro-inflammatory cytokines and environmental stress; immunofluorescence showed p38 is present in both nucleus and cytoplasm of activated cells. In vitro kinase assays, phosphorylation site mapping, immunofluorescence microscopy The Journal of biological chemistry High 7535770
1995 MKK3 and MKK4 were cloned as upstream MAP kinase kinases that phosphorylate and activate p38 MAPK; these MKK isoforms define an independent MAP kinase pathway separate from ERK. Molecular cloning, in vitro kinase assays, pathway epistasis Science High 7839144
1995 JNKK (MKK4) was identified as a dual-specificity kinase that activates both JNK and p38/Mpk2, operating downstream of MEKK and upstream of these MAP kinases. Kinase assays, transfection studies in HeLa cells Science High 7716521
1996 Activated MKK3 and MKK6 selectively increase p38 MAPK activity and stimulate p38-dependent transcription via ATF2 and Elk-1 transcription factors, demonstrating the nucleus as a target of p38 signaling. Cotransfection, luciferase reporter assays, kinase assays Molecular and cellular biology High 8622669
1996 p38 MAP kinase phosphorylates CHOP/GADD153 on Ser78 and Ser81 in vitro; SB203580 abolished stress-inducible CHOP phosphorylation in vivo; phosphorylation enhanced CHOP transactivation activity and inhibitory effect on adipose differentiation. In vitro kinase assay, pharmacological inhibition (SB203580), mutagenesis, reporter assays Science High 8650547
1997 p38 MAP kinase phosphorylates MEF2C in monocytic cells in response to LPS, increasing MEF2C transactivation activity and resulting in increased c-jun gene transcription. Kinase assays, reporter gene assays, in vitro phosphorylation Nature High 9069290
1997 p38/SAPK2 follows an ordered sequential kinetic mechanism where protein substrate (GST-ATF2) binds before ATP; ATP cannot bind in the absence of protein substrate, and ATP binding affects protein substrate affinity. Steady-state kinetics, equilibrium binding with radiolabeled inhibitor, dead-end inhibitor analysis Biochemistry High 9265622
1998 MSK1 is directly activated by SAPK2/p38 (as well as MAPK/ERK2); SB203580 prevents stress-induced MSK1 activation; MSK1 is localized to the nucleus and phosphorylates CREB at Ser133, suggesting p38 mediates stress-induced CREB activation via MSK1. In vitro kinase assays, pharmacological inhibition, cell fractionation/localization, reporter assays The EMBO journal High 9687510
2000 Targeted disruption of p38alpha (MAPK14) gene causes embryonic lethality due to severe defects in placental development, specifically loss of the labyrinth layer, lack of vascularization, and increased apoptosis, establishing an essential role for p38alpha in placental angiogenesis. Gene targeting/knockout mouse, histology, immunohistochemistry Proceedings of the National Academy of Sciences of the United States of America High 10973481
2000 p38alpha and p38beta exhibit differential subcellular localization in adult mouse brain neurons: p38alpha distributes in dendrites and both cytoplasmic/nuclear regions, while p38beta is preferentially nuclear; both isoforms show constitutive activity with the nuclear pool responsible for most activity. Biochemical fractionation, immunohistochemistry, kinase activity assays Journal of neuroscience research Medium 10820433
2000 The p38 pathway functions as a negative regulator of Ras proliferative signaling via a feedback mechanism; Ras activates p38 and downstream kinases MK2 and PRAK, which suppress Ras-induced gene expression and cell proliferation; p38 inhibits Ras activity by blocking JNK activation without affecting ERK; MEK is required for Ras stimulation of the p38 pathway. Kinase assays, dominant-negative/constitutively active mutants, cell proliferation assays, pharmacological inhibition The Journal of biological chemistry High 10978313
2002 A diaryl urea class of p38 MAP kinase inhibitors (including BIRB 796) binds to a novel allosteric site requiring conformational change in the DFG motif; this allosteric pocket is distinct from the ATP-binding site and binding shows slow kinetics consistent with the conformational requirement. X-ray crystallography, kinetic binding studies, IC50 measurements Nature structural biology High 11896401
2003 p38alpha/SAPK2a phosphorylates TAB1 at Ser423, Thr431, and Ser438 in vitro and in vivo; TAB1 phosphorylation by p38alpha mediates a negative feedback control of TAK1, limiting p38alpha activation while synchronizing it with JNK and IKK pathways; enhanced TAK1 activation was observed in p38alpha-deficient cells. In vitro kinase assays, mass spectrometry, pharmacological inhibition, knockout MEFs The EMBO journal High 14592977
2003 Crystal structures of p38alpha bound to quinazolinone and pyridol-pyrimidine inhibitors reveal that their specificity requires a peptide flip between Met109 and Gly110; Gly110 is unique to p38alpha/beta/gamma isoforms; G110A and G110D mutants confirmed that Gly110 determines inhibitor selectivity. X-ray crystallography, site-directed mutagenesis, IC50 measurements Nature structural biology High 12897767
2003 p38alpha is required for Type I interferon-dependent transcriptional regulation via ISRE and GAS elements; p38alpha activates downstream kinases MapKapK-2 and MapKapK-3 in response to IFNalpha; p38alpha activates Msk1, a regulator of histone phosphorylation, downstream of Type I IFN; p38alpha deficiency reduces IFN-dependent antiviral responses. p38alpha knockout embryonic fibroblasts, kinase assays, reporter gene assays The Journal of biological chemistry High 14578350
2004 Single and double activating mutations in human p38alpha (D176A, F327L/S) confer intrinsic kinase activity independent of upstream regulation; these mutations destabilize a hydrophobic core (Tyr69-Phe327-Trp337) near the L16 loop, mimicking conformational changes imposed by dual phosphorylation; active mutants retain substrate specificity and sensitivity to SB-203580. Site-directed mutagenesis, kinase activity assays, structural analysis The Journal of biological chemistry High 15284239
2006 Multiple mechanisms of p38alpha activation exist: MKK3/6 pathway is primary; TAB1 mediates an MKK3/4/6-independent autoactivation accounting for a subset of p38alpha activation; peroxynitrite induces p38alpha phosphorylation via a disulfide complex independent of MKK3/6; different pathways can be simultaneously activated or selectively used by different stimuli. MKK3/6 and MKK4/7 double-knockout MEFs, kinase assays, mutagenesis of p38alpha cysteines The Journal of biological chemistry High 16849316
2006 p38alpha suppresses cell proliferation by antagonizing the JNK/c-Jun pathway; p38alpha-deficient cells show increased proliferation and impaired differentiation; mice deficient in p38alpha are prone to cancer development in carcinogen/oncogene-induced models. Conditional p38alpha knockout mice, cell proliferation assays, cancer model experiments Cell cycle High 17957136
2006 CDC25B is phosphorylated by MAPKAP kinase-2 on multiple sites (S169, S323, S353, S375) and by p38 SAPK on S249; S323-phosphorylated CDC25B is detected at the centrosome during normal cell cycle. Mass spectrometry, phospho-specific antibodies, in vitro kinase assays Cell cycle High 16861915
2007 RhoA is activated in neurons by calcium elevation (glutamate/ischemia) and is required for rapid p38alpha activation and subsequent excitotoxic neuronal death; active RhoA alone was sufficient to activate p38alpha and induce neuronal death sensitive to Bcl-2; this RhoA-p38alpha connection was specific to primary neuronal cultures. Primary neuronal cultures, RhoA dominant-negative/active constructs, kinase assays, Bcl-2 rescue Nature neuroscience High 17369826
2007 p38alpha is required for myoblast cell cycle exit; p38alpha-deficient myoblasts fail to differentiate and form myotubes due to delayed cell cycle exit caused by enhanced JNK/cJun pathway activation, establishing a p38alpha-JNK crosstalk controlling muscle differentiation. p38alpha knockout MEFs/myoblasts, differentiation assays, cell cycle analysis Cell cycle High 17534150
2008 p38alpha/beta MAPK activation during myoblast differentiation is regulated by the cell surface receptor Cdo, which binds scaffold protein JLP and p38alpha/beta; Cdo also interacts with Bnip-2 which binds and regulates Cdc42 and Cdc42-GAP; the Cdo-Bnip-2 interaction stimulates Cdc42 activity which promotes p38alpha/beta activity and differentiation. Co-immunoprecipitation, gain/loss-of-function experiments in myoblasts, kinase assays The Journal of cell biology High 18678706
2008 p38alpha deficiency impairs MEF2C nuclear localization in cardiomyocytes (MEF2C colocalizes with vimentin at perinuclear region), leading to downregulation of MEF2C targets ANF and myocardin; p38alpha deficiency also decreases phosphorylated Mlc2v and causes alpha-actinin accumulation/sarcomere disorganization. p38alpha knockout cells, immunofluorescence, western blot FEBS letters Medium 18314011
2009 p38-gamma directly phosphorylates MyoD on Ser199 and Ser200, resulting in enhanced MyoD occupancy on the myogenin promoter with markedly decreased transcriptional activity; this is associated with histone H3K9 methylation and KMT1A methyltransferase recruitment; p38-gamma deficiency leads to premature Myogenin expression and reduced satellite cell proliferation. In vitro kinase assays, ChIP, site-directed mutagenesis, p38-gamma knockout mice The Journal of cell biology High 20026657
2010 APPL1 functions as a scaffolding protein facilitating adiponectin-stimulated p38 MAPK activation by binding both TAK1 and MKK3 at different regions; in vitro affinity binding and co-immunoprecipitation showed TAK1-MKK3-p38 cascade is scaffolded by APPL1 selectively in response to adiponectin but not TNFα. Co-immunoprecipitation, in vitro affinity binding, overexpression/knockdown in C2C12 cells American journal of physiology. Endocrinology and metabolism High 20978232
2011 p38alpha and p38beta have redundant essential functions during cardiovascular development; combined deletion of p38alpha and p38beta causes major cardiovascular abnormalities at midgestation not seen in single knockouts; knock-in of p38beta under p38alpha promoter shows p38beta cannot replace all p38alpha functions during embryogenesis. Double knockout mice, knock-in mouse models, expression analysis Proceedings of the National Academy of Sciences of the United States of America High 21768366
2011 p38alpha signaling in dendritic cells (not macrophages or T cells) programs TH17 differentiation; DC-specific p38alpha deletion protects mice from TH17-mediated autoimmune neuroinflammation; p38alpha orchestrates cytokine/costimulatory molecule expression and imprints IL-23R signaling in responding T cells. Cell type-specific conditional knockout mice, adoptive transfer, cytokine analysis Nature immunology High 22231518
2011 During mammary acinar morphogenesis, basement membrane detachment stimulates MKK3/6-p38alpha signaling to promote anoikis; p38alpha increases BimEL transcription by phosphorylating ATF-2 and increasing c-Jun abundance; inhibition of p38alpha causes luminal filling resembling DCIS; MKK3/6 knockout mice show ductal lumen occlusion due to reduced anoikis. 3D culture morphogenesis model, knockout mice, gene expression analysis, pharmacological inhibition Science signaling High 21610252
2011 p38alpha and p38beta determine cholinergic transdifferentiation of sympathetic neurons in response to neuropoietic cytokines CNTF/LIF; p38 inhibition blocks upregulation of nuclear matrix protein Satb2 and cholinergic markers without affecting STAT3 phosphorylation; p38beta knockout mice show loss of cholinergic cells in stellate ganglion. p38beta knockout mice, pharmacological inhibition, overexpression in postmitotic neurons The Journal of neuroscience High 21865449
2012 MAPK14 (p38alpha), activated by the GADD45B-MAP3K4 signaling complex, localizes to autophagosomes and directly phosphorylates ATG5 at Thr75 (evolutionarily conserved); phospho-mimetic ATG5 impairs autophagosome-lysosome fusion and autophagy; MAPK14-deficient and GADD45B-deficient cells show increased autophagic flux. In vitro kinase assays, autophagosome-lysosome fusion assays, ATG5 phospho-mutant reconstitution in ATG5-deficient cells, autophagic flux measurement Autophagy High 23235332
2012 p38alpha deficiency in myoblasts reduces cell fusion capacity and multinucleated myotube formation; comparative expression profiling identified tetraspanin CD53 as a p38alpha-upregulated gene required for cell fusion; this was confirmed ex vivo and in vivo during myofiber regeneration. p38alpha-deficient myoblasts, expression profiling, CD53 functional validation ex vivo and in vivo Journal of molecular cell biology High 22847234
2013 PRMT1 directly methylates p38alpha in vitro and associates with p38alpha in cells by co-immunoprecipitation; PRMT1 acts upstream of p38alpha to enhance p38 MAPK activation and promote erythroid differentiation; PRMT1's effect on differentiation was abolished in p38alpha-knockdown cells. In vitro methylation assay, co-immunoprecipitation, knockdown experiments, differentiation assays PloS one High 23483889
2014 p38alpha directly phosphorylates and activates the pro-death Bcl-2 family member Bax in dystrophic muscle, inducing myofiber death through a mitochondrial-dependent pathway; muscle-specific deletion of Bax (but not Tp53) significantly reduced dystrophic pathology in MKK6-transgenic mice. Conditional muscle knockout mice, MKK6 transgenic mice, in vitro phosphorylation, genetic epistasis Human molecular genetics High 24876160
2014 MKK6 (but not MKK3) functions as upstream kinase of p38alpha in ectodermal appendages; p38alpha acts downstream of BMP2/7 signaling; p38alpha deletion in ectodermal cells causes impaired tooth cusp patterning and defective dental enamel due to ameloblast differentiation defects; amelogenin, β4-integrin, and p21 expression are reduced. Conditional p38alpha knockout (K14-Cre), MKK3/6 knockout mice, BMP stimulation of explant cultures The Journal of biological chemistry High 25406311
2014 Chemical phosphorylation of p38alpha activation loop showed that pCys at position 180 (mimicking pThr) alone is sufficient to activate p38alpha to phosphorylate ATF2; position 172 phosphorylation did not activate; Type II inhibitors (but not Type I) can inhibit the phosphorylated form of p38alpha. Chemical protein modification (tag-and-modify), in vitro kinase assays with ATF2, inhibitor profiling Journal of the American Chemical Society High 24393126
2014 Docking interaction of p38alpha with the C-terminal fragment of its substrate MK2 allosterically enhances ATP and phosphoacceptor binding to the active site, accelerating the phosphotransfer reaction; p38alpha phosphorylation and ATP loading collaboratively induce the active conformation before MK2 docking. Solution NMR spectroscopy, kinetic assays Nature structural & molecular biology High 25038803
2014 MAPK14 drives metabolic reprogramming during starvation: it increases SLC2A3 expression via HIF1A protein stabilization, and mediates a shift from glycolysis to the pentose phosphate pathway through PFKFB3 degradation (via KEN box and DSG motif Ser273 recognized by distinct E3 ligase complexes); this sustains NADPH production and reduces ROS and autophagy. siRNA knockdown, proteasome inhibition, PFKFB3 mutant reconstitution, metabolic flux assays Autophagy High 25046111
2015 Mitophagy in HeLa cells under starvation or hypoxia primarily occurs through an alternative autophagy pathway requiring RAB9A and RAB9B; both MAPK1/ERK2 and MAPK14/p38 signaling pathways are required for this mitophagy, as their knockdown severely suppressed mitochondrial degradation. pH-sensitive Keima reporter, siRNA knockdown of MAPK14, RAB9A/B, ATG5/7/12, Atg5 KO MEFs Autophagy High 25831013
2016 MAPK14/p38alpha directly phosphorylates ULK1, inhibiting its activity; in microglia, p38alpha senses LPS stimulus and phosphorylates/inhibits ULK1, thereby relieving autophagic brake on inflammation and enabling full inflammatory response. Kinase assays, p38alpha inhibition/knockdown, ULK1 phosphorylation analysis in microglia Autophagy Medium 29749797
2016 p38alpha activation downstream of Gq-coupled GPCRs (phenylephrine, angiotensin II) promotes HuR cytoplasmic translocation in cardiomyocytes; p38-dependent HuR activation is required for hypertrophic growth and modulates NFAT transcriptional activity. siRNA knockdown, pharmacological inhibition of p38, NFAT-luciferase reporter, cell size measurement Cellular signalling Medium 27521603
2016 p38 MAPK pathway regulates Hippo signaling: in mammalian cells, MKK3 (Lic homologue) promotes nuclear localization of YAP via actin cytoskeleton; upregulation/downregulation of p38 pathway regulates YAP-mediated transcription; in Drosophila, Mekk1-Lic-p38b cascade inhibits Hippo signaling via promoting F-actin and Jub phosphorylation. Epistasis analysis in Drosophila, siRNA knockdown and overexpression in mammalian cells, actin staining, YAP reporter assays Journal of molecular cell biology Medium 27402810
2017 Sustained p38alpha activation induces metabolic changes including glucose dependence, increased glutamine consumption, enhanced respiration, and elevated mitochondrial ROS; the p38alpha-activated kinase MAPKAPK2 (MK2) orchestrates these metabolic changes; increased mitochondrial superoxide contributes to reduced cell survival. Inducible p38alpha activation system, metabolic flux assays, MK2 knockout Scientific reports High 28900160
2017 p38alpha deficiency in liver hepatocytes induces actin disassembly, cytokinesis failure, and binucleation during aging; this is associated with cyclin B1 overexpression, RhoA/Cdc42 hyperactivation, and HSP27 inactivation; HSP27 silencing recapitulates actin cytoskeleton loss, suggesting p38alpha-HSP27 axis maintains actin dynamics. Liver-specific p38alpha knockout mice at multiple ages, actin staining, flow cytometry, kinase activity measurement PloS one High 28166285
2018 TAB1-induced p38alpha autoactivation critically depends on Thr185; T185G mutation prevents an intramolecular hydrogen bond with Asp150, disrupting the effect of TAB1 binding on the activation segment (Thr180 phosphorylation) without affecting TAB1 binding or MKK-mediated activation; myocardial cells expressing T185G were resistant to ischemic injury. Crystal structure of p38alpha-TAB1 complex, site-directed mutagenesis (T185G), in vitro and in vivo kinase assays, cardiomyocyte injury model Molecular and cellular biology High 29229647
2018 The TAB1-p38alpha interaction was further characterized by solving the crystal structure of phospho-p38alpha with full-length TAB1 (residues 1-438); TAB1 knock-in mice with 4 substituted docking residues showed reduced myocardial infarction volume and disabled TAB1 transphosphorylation while only mildly attenuating p38alpha activation during ischemia; small molecule fragments can disrupt p38alpha-TAB1 interaction. X-ray crystallography, knock-in mouse model, in vivo ischemia model, fragment-based drug discovery JCI insight High 30135318
2018 p38alpha deficiency in skeletal muscle protects against denervation-induced muscle atrophy; CAMK2B was identified as a potential downstream target of p38alpha; pharmacological inhibition of CAMK2B suppresses denervation-induced muscle atrophy. Muscle-specific p38alpha knockout mice, denervation model, pharmacological CAMK2B inhibition Scientific reports Medium 29899565
2018 p38alpha deficiency in platelets impairs p38alpha/MAPKAPK2/HSP27 and p38alpha/cytosolic phospholipase A2 pathways; p38alpha activation is one of the earliest events in platelets after agonist or ROS stimulation; ERK1/2 plays distinct roles in receptor- versus ROS-induced p38-mediated platelet activation. Platelet-specific conditional knockout mice, signaling pathway analysis, thrombosis models Arteriosclerosis, thrombosis, and vascular biology High 28982666
2019 Sustained p38alpha activation is sufficient to trigger autophagosome formation and enhance autophagic flux through concurrent increased mitochondrial ROS and phosphorylation of ULK1 on Ser-555; p38alpha-induced macroautophagy determines that cancer cells enter senescence instead of apoptosis, protecting from chemotherapy-induced apoptosis. Inducible p38alpha activation, autophagic flux assays, ULK1 phosphorylation, cell fate analysis Cell death & disease High 31092814
2019 p38alpha negatively regulates an angiogenic program in mesenchymal stem/stromal cells (MSCs) including TGF-β-induced acquisition of endothelial phenotype (mesenchymal-endothelial transition); this is mediated by both TGF-β and JNK pathways and negatively regulated by p38alpha; p38alpha ablation in mesenchymal cells increases tumorigenesis with enhanced angiogenesis. Conditional knockout mice, genetic tumor models, in vitro differentiation assays Nature communications High 31296856
2019 Macrophage-specific p38alpha promotes steatohepatitis through induction of pro-inflammatory M1 polarization (CXCL2, IL-1β, CXCL10, IL-6 secretion); p38αΔMΦ mice showed M2 anti-inflammatory polarization; co-culture experiments confirmed that p38alpha-deleted macrophages attenuate hepatocyte steatosis via decreased cytokine secretion. Macrophage-specific and hepatocyte-specific conditional knockout mice, co-culture systems, flow cytometry Journal of hepatology High 30914267
2019 Myeloid cell p38alpha promotes intestinal IGF-1 production in macrophages; IGF-1 produced by myeloid cells mediates colon inflammation and tumorigenesis downstream of p38alpha; myeloid-specific p38alpha downregulation protects against colitis-associated tumorigenesis. Myeloid-specific conditional knockout, pharmacological p38 inhibition, genetic and pharmacological IGF-1 pathway manipulation EMBO molecular medicine High 29907597
2019 VSMC-MAPK14 is required for injury-induced neointima formation; MAPK14 suppresses VSMC differentiation (contractile phenotype) and promotes proliferation; MAPK14 activates proinflammatory gene expression in VSMCs via a p65/NFkB-dependent pathway; NOX4 contributes to MAPK14 suppression of the VSMC contractile phenotype. Inducible SMC-MAPK14 knockout mice, carotid ligation model, pharmacological inhibition, RNA array, lineage tracing Redox biology High 30771750
2019 Deletion of p38alpha in microglia attenuates multiple pro-inflammatory responses following TBI, notably reducing cytokine/chemokine production and inflammatory monocyte recruitment to brain, and preventing persistent microglial morphological activation. CX3CR1-Cre conditional knockout mice, controlled cortical impact TBI model, cytokine profiling, flow cytometry Journal of neuroinflammation High 31077217
2019 Neuronal p38alpha activity increases with age; neuron-specific deletion of p38alpha reduces age-associated elevation of p38MAPK activity, neuronal loss, and cognitive decline; aged neuron-specific p38alpha knockout mice show elevated neural stem cell numbers in hippocampus and subventricular zone. CamkII-Cre conditional knockout mice, cognitive testing, neural stem cell quantification Aging cell High 31560167
2020 p38alpha promotes KrasG12V-driven lung cancer cell proliferation and malignization in an epithelial cell-autonomous manner; p38alpha promotes expression of TIMP-1, which stimulates cell proliferation in an autocrine manner; despite acting as tumor suppressor in healthy alveolar progenitors, p38alpha contributes to lung cancer progression. Conditional knockout in lung cancer mouse models, TIMP-1 functional validation, in vivo tumor growth assays Proceedings of the National Academy of Sciences of the United States of America High 31969449
2020 Proximity-dependent labeling (BioID2 fused to p38alpha) identified 37 interacting proteins including known pathway components (MKK3, MAPKAPK2, TAB2, c-jun) and a cluster of zinc finger domain proteins; XPA (DNA damage response factor) was validated as a p38alpha interactor by fluorescence imaging and co-IP, promoted by UV irradiation. BioID2 proximity labeling, mass spectrometry, co-immunoprecipitation, fluorescence imaging Protein science Medium 32189389
2021 MKK6 engages p38 not only via the hydrophobic docking groove but also influences helix αF (organizing the kinase core); the p38 conserved docking (CD) site is much less affected by MKK6 binding compared to MAPK phosphatases; these interactions are conserved independent of MKK6 activation state. NMR spectroscopy, isothermal titration calorimetry with full-length MKK6 and p38 Protein science High 33554397
2024 MKP1 (MAPK phosphatase 1) dephosphorylates and inactivates p38alpha in lung myofibroblasts; MKP1-mediated p38alpha dephosphorylation promotes myofibroblast dedifferentiation and restores apoptosis sensitivity; fibroblast-specific MKP1 deletion after peak bleomycin fibrosis abrogated spontaneous resolution, which was restored by p38alpha inhibitor VX-702. Gain/loss-of-function studies, fibroblast-specific conditional knockout, pharmacological rescue with p38alpha inhibitor The Journal of clinical investigation High 38512415
2025 Lobeline binds directly to MAPK14; upon binding, lobeline prevents nuclear translocation of MAPK14, resulting in decreased phosphorylated p53; decreased p-p53 relieves negative transcriptional regulation of SLURP1, enhancing SLURP1 transcription and secretion which promotes M1 TAM polarization and inhibits M2 polarization. Target-responsive accessibility profiling, nuclear fractionation, ChIP/transcription analysis, in vivo tumor model Advanced science Medium 39840525

Source papers

Stage 0 corpus · 130 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
2006 Global, in vivo, and site-specific phosphorylation dynamics in signaling networks. Cell 2861 17081983
1994 A protein kinase involved in the regulation of inflammatory cytokine biosynthesis. Nature 2822 7997261
1994 A MAP kinase targeted by endotoxin and hyperosmolarity in mammalian cells. Science (New York, N.Y.) 2380 7914033
2005 Towards a proteome-scale map of the human protein-protein interaction network. Nature 2090 16189514
1995 Pro-inflammatory cytokines and environmental stress cause p38 mitogen-activated protein kinase activation by dual phosphorylation on tyrosine and threonine. The Journal of biological chemistry 2014 7535770
2005 A human protein-protein interaction network: a resource for annotating the proteome. Cell 1704 16169070
2002 Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences. Proceedings of the National Academy of Sciences of the United States of America 1479 12477932
1995 Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms. Science (New York, N.Y.) 1428 7839144
2010 Mechanisms and functions of p38 MAPK signalling. The Biochemical journal 1342 20626350
2010 Network organization of the human autophagy system. Nature 1286 20562859
1997 Mitotic and G2 checkpoint control: regulation of 14-3-3 protein binding by phosphorylation of Cdc25C on serine-216. Science (New York, N.Y.) 1191 9278512
1996 MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway. Molecular and cellular biology 1160 8622669
2015 The BioPlex Network: A Systematic Exploration of the Human Interactome. Cell 1118 26186194
1999 Regulation of 4E-BP1 phosphorylation: a novel two-step mechanism. Genes & development 1096 10364159
2017 Architecture of the human interactome defines protein communities and disease networks. Nature 1085 28514442
2001 Nerve growth factor signaling, neuroprotection, and neural repair. Annual review of neuroscience 1029 11520933
2015 A human interactome in three quantitative dimensions organized by stoichiometries and abundances. Cell 1015 26496610
1998 RAFT1 phosphorylation of the translational regulators p70 S6 kinase and 4E-BP1. Proceedings of the National Academy of Sciences of the United States of America 949 9465032
2004 Immunoaffinity profiling of tyrosine phosphorylation in cancer cells. Nature biotechnology 916 15592455
1998 Mitogen- and stress-activated protein kinase-1 (MSK1) is directly activated by MAPK and SAPK2/p38, and may mediate activation of CREB. The EMBO journal 842 9687510
1994 Interleukin-1 activates a novel protein kinase cascade that results in the phosphorylation of Hsp27. Cell 805 7923354
2010 Feedback between p21 and reactive oxygen production is necessary for cell senescence. Molecular systems biology 775 20160708
1996 Stress-induced phosphorylation and activation of the transcription factor CHOP (GADD153) by p38 MAP Kinase. Science (New York, N.Y.) 750 8650547
2001 Hierarchical phosphorylation of the translation inhibitor 4E-BP1. Genes & development 742 11691836
2002 Inhibition of p38 MAP kinase by utilizing a novel allosteric binding site. Nature structural biology 730 11896401
1995 Identification of a dual specificity kinase that activates the Jun kinases and p38-Mpk2. Science (New York, N.Y.) 721 7716521
2012 Cardiac natriuretic peptides act via p38 MAPK to induce the brown fat thermogenic program in mouse and human adipocytes. The Journal of clinical investigation 720 22307324
2021 Dual proteome-scale networks reveal cell-specific remodeling of the human interactome. Cell 705 33961781
2012 A census of human soluble protein complexes. Cell 689 22939629
1997 Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation. Nature 667 9069290
2011 Phylogenetic-based propagation of functional annotations within the Gene Ontology consortium. Briefings in bioinformatics 656 21873635
2000 Essential role for p38alpha mitogen-activated protein kinase in placental angiogenesis. Proceedings of the National Academy of Sciences of the United States of America 324 10973481
1999 Both Erk and p38 kinases are necessary for cytokine gene transcription. American journal of respiratory cell and molecular biology 249 10101008
2003 Feedback control of the protein kinase TAK1 by SAPK2a/p38alpha. The EMBO journal 245 14592977
2007 The pathways to tumor suppression via route p38. Trends in biochemical sciences 229 17624785
2007 Increased activation of p38 MAPK in COPD. The European respiratory journal 215 17959643
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 175 25831013
2006 p38 MAPK in development and cancer. Cell cycle (Georgetown, Tex.) 174 16627995
2003 Structural basis for p38alpha MAP kinase quinazolinone and pyridol-pyrimidine inhibitor specificity. Nature structural biology 174 12897767
2019 Macrophage p38α promotes nutritional steatohepatitis through M1 polarization. Journal of hepatology 172 30914267
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
2000 The p38 pathway provides negative feedback for Ras proliferative signaling. The Journal of biological chemistry 149 10978313
2012 Roles of p38 MAPKs in invasion and metastasis. Biochemical Society transactions 122 22260669
2019 Regulation of tumor angiogenesis and mesenchymal-endothelial transition by p38α through TGF-β and JNK signaling. Nature communications 112 31296856
2007 Rho mediates calcium-dependent activation of p38alpha and subsequent excitotoxic cell death. Nature neuroscience 105 17369826
2003 Role of p38alpha Map kinase in Type I interferon signaling. The Journal of biological chemistry 103 14578350
2009 The p38alpha kinase plays a central role in inflammation. Current topics in medicinal chemistry 96 19747121
2012 Signaling via the kinase p38α programs dendritic cells to drive TH17 differentiation and autoimmune inflammation. Nature immunology 93 22231518
1997 Kinetic mechanism for p38 MAP kinase. Biochemistry 93 9265622
2009 p38-{gamma}-dependent gene silencing restricts entry into the myogenic differentiation program. The Journal of cell biology 92 20026657
2008 A Cdo-Bnip-2-Cdc42 signaling pathway regulates p38alpha/beta MAPK activity and myogenic differentiation. The Journal of cell biology 91 18678706
2021 Current status and future prospects of p38α/MAPK14 kinase and its inhibitors. European journal of medicinal chemistry 88 33524689
2006 The p38 transduction pathway in prostatic neoplasia. The Journal of pathology 80 16369914
2006 Multiple activation mechanisms of p38alpha mitogen-activated protein kinase. The Journal of biological chemistry 77 16849316
2010 APPL1 mediates adiponectin-stimulated p38 MAPK activation by scaffolding the TAK1-MKK3-p38 MAPK pathway. American journal of physiology. Endocrinology and metabolism 71 20978232
2007 Genetic deficiency of p38alpha reveals its critical role in myoblast cell cycle exit: the p38alpha-JNK connection. Cell cycle (Georgetown, Tex.) 71 17534150
2019 Autophagy-induced senescence is regulated by p38α signaling. Cell death & disease 69 31092814
2004 Active mutants of the human p38alpha mitogen-activated protein kinase. The Journal of biological chemistry 68 15284239
2012 Comparative expression profiling identifies differential roles for Myogenin and p38α MAPK signaling in myogenesis. Journal of molecular cell biology 67 22847234
2005 Structural comparison of p38 inhibitor-protein complexes: a review of recent p38 inhibitors having unique binding interactions. Current topics in medicinal chemistry 65 16178743
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
2019 Vascular smooth muscle-MAPK14 is required for neointimal hyperplasia by suppressing VSMC differentiation and inducing proliferation and inflammation. Redox biology 52 30771750
2011 Genetic analysis of specific and redundant roles for p38alpha and p38beta MAPKs during mouse development. Proceedings of the National Academy of Sciences of the United States of America 52 21768366
2022 Crosstalk between p38 MAPK and GR Signaling. International journal of molecular sciences 47 35328742
2019 Deletion of p38α MAPK in microglia blunts trauma-induced inflammatory responses in mice. Journal of neuroinflammation 45 31077217
2016 Activation of HuR downstream of p38 MAPK promotes cardiomyocyte hypertrophy. Cellular signalling 41 27521603
2014 P38α MAPK underlies muscular dystrophy and myofiber death through a Bax-dependent mechanism. Human molecular genetics 41 24876160
2011 p38α Signaling Induces Anoikis and Lumen Formation During Mammary Morphogenesis. Science signaling 41 21610252
2018 Chaihu-Shugan-San exerts an antidepressive effect by downregulating miR-124 and releasing inhibition of the MAPK14 and Gria3 signaling pathways. Neural regeneration research 39 29863014
2016 Regulation of Hippo signalling by p38 signalling. Journal of molecular cell biology 39 27402810
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
2006 CDC25B phosphorylation by p38 and MK-2. Cell cycle (Georgetown, Tex.) 39 16861915
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 34 29899565
2017 Platelet-Specific p38α Deficiency Improved Cardiac Function After Myocardial Infarction in Mice. Arteriosclerosis, thrombosis, and vascular biology 34 28982666
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
2018 The p38α Stress Kinase Suppresses Aneuploidy Tolerance by Inhibiting Hif-1α. Cell reports 33 30332653
2023 P38 kinase in gastrointestinal cancers. Cancer gene therapy 32 37248432
2012 Mechanism for p38α-mediated experimental autoimmune encephalomyelitis. The Journal of biological chemistry 32 22637476
2021 BMI1 Drives Steroidogenesis Through Epigenetically Repressing the p38 MAPK Pathway. Frontiers in cell and developmental biology 31 33928089
2014 p38α MAPK is required for tooth morphogenesis and enamel secretion. The Journal of biological chemistry 31 25406311
2019 Progesterone induces cell apoptosis via the CACNA2D3/Ca2+/p38 MAPK pathway in endometrial cancer. Oncology reports 30 31746409
2004 SAR of benzoylpyridines and benzophenones as p38alpha MAP kinase inhibitors with oral activity. Bioorganic & medicinal chemistry letters 29 15177483
2023 Impact of curcumin on p38 MAPK: therapeutic implications. Inflammopharmacology 28 37498375
2024 MAPK phosphatase 1 inhibition of p38α within lung myofibroblasts is essential for spontaneous fibrosis resolution. The Journal of clinical investigation 27 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 26 32243890
2018 Myeloid p38α signaling promotes intestinal IGF-1 production and inflammation-associated tumorigenesis. EMBO molecular medicine 26 29907597
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
2021 p38 Signalling Pathway. International journal of molecular sciences 25 33498296
2020 In silico identification of MAPK14-related lncRNAs and assessment of their expression in breast cancer samples. Scientific reports 25 32433496
2020 Cannabidiol induces osteoblast differentiation via angiopoietin1 and p38 MAPK. Environmental toxicology 25 32656944
2020 In silico molecular target prediction unveils mebendazole as a potent MAPK14 inhibitor. Molecular oncology 25 33021050
2017 Induction of oxidative metabolism by the p38α/MK2 pathway. Scientific reports 25 28900160
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 24 27871059
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
2022 Shikonin triggers GSDME-mediated pyroptosis in tumours by regulating autophagy via the ROS-MAPK14/p38α axis. Phytomedicine : international journal of phytotherapy and phytopharmacology 23 36610142
2016 Afzelin positively regulates melanogenesis through the p38 MAPK pathway. Chemico-biological interactions 23 27287415
2016 BMP7 retards peripheral myelination by activating p38 MAPK in Schwann cells. Scientific reports 23 27491681
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
2023 SiNPs induce ferroptosis in HUVECs through p38 inhibiting NrF2 pathway. Frontiers in public health 22 36844840
2022 p38 activation and viral infection. Expert reviews in molecular medicine 22 35060846
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
2020 Activation of GPR40 induces hypothalamic neurogenesis through p38- and BDNF-dependent mechanisms. Scientific reports 22 32632088
2018 Release the autophage brake on inflammation: The MAPK14/p38α-ULK1 pedal. Autophagy 22 29749797
2013 The synthetic flavonoid WYC02-9 inhibits colorectal cancer cell growth through ROS-mediated activation of MAPK14 pathway. Life sciences 22 23624232
2008 Ouabain inhibits p38 activation in thymocytes. Cell biology international 22 18703152
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
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
2020 The role of miR-128-3p through MAPK14 activation in the apoptosis of GC2 spermatocyte cell line following heat stress. Andrology 20 33089633
2018 TAB1-Induced Autoactivation of p38α Mitogen-Activated Protein Kinase Is Crucially Dependent on Threonine 185. Molecular and cellular biology 20 29229647
2018 The TAB1-p38α complex aggravates myocardial injury and can be targeted by small molecules. JCI insight 20 30135318
2013 The synthetic flavonoid WYC02-9 inhibits cervical cancer cell migration/invasion and angiogenesis via MAPK14 signaling. Gynecologic oncology 20 24145114
2020 Design, synthesis and anti-inflammatory activity of imidazol-5-yl pyridine derivatives as p38α/MAPK14 inhibitor. Bioorganic & medicinal chemistry 19 33422910
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 18 18314011
2000 Tensin can induce JNK and p38 activation. Biochemical and biophysical research communications 18 10860821
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) 17 39840525
2019 Neuronal p38α mediates age-associated neural stem cell exhaustion and cognitive decline. Aging cell 17 31560167
2018 Glabridin inhibits osteosarcoma migration and invasion via blocking the p38- and JNK-mediated CREB-AP1 complexes formation. Journal of cellular physiology 17 30146723
2022 Androgen receptor suppresses inflammatory response of airway epithelial cells in allergic asthma through MAPK1 and MAPK14. Human & experimental toxicology 16 35982617
2021 The interaction of p38 with its upstream kinase MKK6. Protein science : a publication of the Protein Society 16 33554397
2017 p38α regulates actin cytoskeleton and cytokinesis in hepatocytes during development and aging. PloS one 16 28166285