Affinage

MAPK11

Mitogen-activated protein kinase 11 · UniProt Q15759

Audit flag: ungrounded claim
Length
364 aa
Mass
41.4 kDa
Annotated
2026-06-10
100 papers in source corpus 48 papers cited in narrative 48 extracted findings
Cross-family judge vs UniProt: Affinage preferred faithfulness: 6/6 claims corpus-supported (100%)

Mechanistic narrative

Synthesis pass · prose summary of the discoveries below

MAPK11 (p38beta) is a stress- and cytokine-activated MAP kinase that requires dual phosphorylation of its TGY motif for catalysis and is preferentially activated by MKK6/MEK6, with strong transactivation of substrates such as ATF2 and Sap-1a (PMID:8663524, PMID:9235954). It is distinguished from its paralog p38alpha both structurally and functionally: its crystal structure reveals a constricted ATP-binding pocket relative to p38alpha (PMID:19622861), and it possesses an intrinsic autophosphorylation activity localized to a 13-residue alpha-G helix/MAPK insert region that is restrained in vivo by an N-terminal/C-terminal interaction and by inhibitory autophosphorylation at T241 and S261 in addition to the activating T180 site (PMID:25006254, PMID:26976637). p38beta executes a distinct substrate program: it acts as a priming kinase that phosphorylates glycogen synthase to enable GSK-3 (PMID:14680475), phosphorylates Raptor at Ser863/Ser771 to activate mTORC1 selectively under arsenite stress (PMID:21757713), phosphorylates STIM1 to switch off store-operated Ca2+ entry (PMID:23625915), phosphorylates mitochondrial MnSOD at Thr79/Ser106 to sustain antioxidant defense (PMID:27930699), and phosphorylates SNX27 at Ser51 to remodel its cargo pocket and inhibit endocytic recycling (PMID:33605979). A dominant theme is its control of skeletal muscle catabolism, where it uniquely phosphorylates C/EBPbeta at Thr-188 to drive atrogin1/MAFbx expression, phosphorylates p300 at Ser-12 to promote C/EBPbeta acetylation, and phosphorylates ULK1 at Ser555 to activate autophagy, collectively mediating activin A-, tumor-, and cachexia-associated muscle wasting (PMID:23046544, PMID:31225455, PMID:33355181). In contrast to the pro-apoptotic actions of p38alpha, p38beta is broadly pro-survival across mesangial cells, cardiomyocytes, and endothelial cells (PMID:11500933, PMID:20724307, PMID:22454), and its signaling output is spatially restricted because the p38beta-PRAK complex is excluded from the nucleus via residues Gly145/Val156 (PMID:18268017). It also drives HSP27-dependent actin remodeling and migration downstream of VEGFR2 (PMID:10744763, PMID:16966330), mediates cholinergic transdifferentiation of sympathetic neurons and spinal microglial beta-endorphin expression in pain processing (PMID:21865449, PMID:28202578), modulates mutant huntingtin levels (PMID:29151587), and serves as a host dependency factor for SARS-CoV-2 replication (PMID:37345956). Genetic knockout establishes that p38beta is dispensable for inflammatory cytokine responses, where p38alpha predominates (PMID:16287858, PMID:17855341).

Mechanistic history

Synthesis pass · year-by-year structured walk · 20 steps
  1. 1996 High

    Established MAPK11 as a bona fide stress-activated MAP kinase with a defined activation requirement and a substrate preference distinct from p38alpha, answering whether the new isoform was catalytically and regulatorily independent.

    Evidence In vitro kinase assays, TGY-motif mutagenesis, phosphopeptide mapping and reporter assays defining MKK6 as preferred activator and ATF2/Sap-1a as preferred substrates

    PMID:8663524 PMID:9235954

    Open questions at the time
    • Did not resolve in vivo substrate repertoire beyond transcription factors
    • Physiological context of MKK6 selectivity not addressed
  2. 1998 High

    Placed p38/MAPK11 upstream of MSK1-CREB signaling, linking stress kinase activity to transcriptional output via a downstream effector kinase.

    Evidence In vitro reconstitution of MSK1 activation plus SB203580 inhibition in cells, with MSK1 phosphorylating CREB Ser133

    PMID:9687510

    Open questions at the time
    • Inhibitor does not distinguish p38alpha from p38beta
    • Isoform-specific contribution to CREB activation not isolated
  3. 1998 Medium

    Revealed an isoform divergence in cell-fate control, showing p38beta is pro-survival/anti-apoptotic where p38alpha is pro-apoptotic.

    Evidence Isoform overexpression with caspase, nuclear condensation, DNA fragmentation and Bcl-2 rescue assays under Fas/UV challenge

    PMID:9632706

    Open questions at the time
    • Overexpression may not reflect endogenous stoichiometry
    • Molecular substrates mediating survival not identified
  4. 1999 High

    Connected the p38/MAPK11 pathway to cytoskeletal remodeling and migration through HSP27 phosphorylation via MAPKAPK2/3, defining a non-transcriptional output.

    Evidence SB203580 inhibition, non-phosphorylatable HSP27 mutants, F-actin staining and migration assays in endothelial cells

    PMID:10207622 PMID:9832563

    Open questions at the time
    • Pharmacology and pathway summaries do not isolate p38beta from p38alpha
    • Direct p38beta-HSP27 axis not demonstrated
  5. 2000 High

    Mapped the receptor-proximal pathway driving p38-dependent actin remodeling, identifying VEGFR2 as the specific receptor input.

    Evidence VEGFR1/VEGFR2-selective cell lines, neutralizing antibodies, SB203580 and HSP90 rescue with migration assays

    PMID:10744763

    Open questions at the time
    • Isoform identity of activated p38 not resolved
    • Direct kinase-substrate steps downstream of VEGFR2 not fully reconstituted
  6. 2004 High

    Dissected the upstream cascade from VEGFR2-Tyr1214 through Cdc42 to p38, and later through a Fyn-Nck-PAK2 module, establishing how a receptor selectively engages p38-MAPKAPK2 actin signaling.

    Evidence VEGFR2 Y1214F mutagenesis, dominant-negative/constitutively active Cdc42, reciprocal co-IP and chemical/dominant-negative Fyn inhibition with stress-fiber and migration readouts

    PMID:14724572 PMID:16966330

    Open questions at the time
    • p38beta-specific role within this VEGFR2 cascade not separated from p38alpha
    • Direct effector phosphorylation by the relevant isoform not shown
  7. 2004 High

    Identified the first p38beta-preferred metabolic substrate, showing it functions as a priming kinase for GSK-3 on glycogen synthase.

    Evidence In vitro kinase and substrate-binding assays, phosphopeptide mapping, isoform affinity comparison and co-incubation with GSK-3

    PMID:14680475

    Open questions at the time
    • In vivo relevance to glycogen metabolism not established
    • Upstream activator in this context not defined
  8. 2005 High

    Genetic knockout resolved the physiological essentiality of MAPK11, showing it is dispensable for inflammation and immune development, with p38alpha predominant.

    Evidence Germline p38beta knockout with multi-pathway kinase profiling, cytokine ELISA and TNFDeltaARE disease cross; later corroborated by T106M knock-in chemical genetics

    PMID:16287858 PMID:17855341

    Open questions at the time
    • Compensation by p38alpha not formally excluded for all phenotypes
    • Did not address non-immune tissue-specific roles
  9. 2005 High

    Established isoform- and cell-type-specific in vivo functions for MAPK11 in nervous tissue and vascular biology, distinguishing it from p38alpha by selective knockdown.

    Evidence Isoform-specific antisense in spinal microglia with pain behavior assays; p38beta knockout/rescue for CO-induced caveolin-1; dominant-negative isoform comparisons

    PMID:11500933 PMID:15748168 PMID:16051704

    Open questions at the time
    • Direct substrates in microglial pain signaling not identified
    • Mechanism of CO-induced p38beta activation unresolved
  10. 2008 High

    Explained the divergent subcellular signaling of the two isoforms by mapping the residues that exclude the p38beta-PRAK complex from the nucleus.

    Evidence Chimeric and point mutants (Gly145/Val156 vs Asp145/Leu156), subcellular fractionation, nuclear import assays and proliferation readouts

    PMID:18268017

    Open questions at the time
    • Generalizability of cytosolic restriction to other p38beta partners not tested
    • Consequences for the full p38beta substrate set not mapped
  11. 2009 High

    Provided a structural basis for p38beta's distinct inhibitor and substrate behavior by solving its crystal structure and revealing a reduced ATP pocket.

    Evidence X-ray crystallography of p38beta versus p38alpha mutants at 2.05 Angstrom

    PMID:19622861

    Open questions at the time
    • Structure of active/phosphorylated state and substrate complexes not determined
    • Link to autophosphorylation mechanism not yet structural
  12. 2011 High

    Defined developmental and signaling roles, showing p38beta partners with p38alpha for embryonic cardiovascular development and selectively activates mTORC1 via Raptor under arsenite stress.

    Evidence Double-knockout and p38beta knock-in mice for development; co-IP and in vitro phosphorylation of Raptor Ser863/Ser771 with stimulus-specificity controls

    PMID:21757713 PMID:21768366 PMID:21865449

    Open questions at the time
    • Why arsenite uniquely couples p38beta to Raptor is unclear
    • Non-redundant developmental substrates of p38beta not identified
  13. 2012 High

    Identified the defining p38beta-specific catabolic mechanism in muscle: phosphorylation of C/EBPbeta at Thr-188 to drive atrogin1/MAFbx expression.

    Evidence Phosphopeptide mapping, ChIP, C/EBPbeta T188A mutagenesis, siRNA, and C/EBPbeta-null mice with in vivo muscle injection

    PMID:23046544

    Open questions at the time
    • Upstream activator of p38beta in catabolic muscle not fully defined here
    • Did not yet integrate autophagy or acetylation arms
  14. 2013 High

    Expanded the p38beta substrate map to Ca2+ homeostasis and revealed a selective stabilizing partner, showing direct STIM1 phosphorylation and ILK-dependent control of p38beta levels.

    Evidence Isoform-specific siRNA with STIM1 phosphorylation and Ca2+ entry assays; reciprocal co-IP, BiFC/PLA and MG132 rescue for ILK-p38beta

    PMID:23435415 PMID:23625915

    Open questions at the time
    • Phosphosites on STIM1 not individually mapped
    • Mechanism of ILK-mediated p38beta protein protection not detailed
  15. 2014 High

    Resolved the autoregulatory logic of MAPK11, identifying both an activating autophosphorylation element and inhibitory autophosphorylation sites that tune basal activity.

    Evidence In vitro autophosphorylation, domain-swap chimeras, mass spectrometry of T241/S261, mutagenesis and tissue phosphorylation analysis

    PMID:25006254 PMID:26976637

    Open questions at the time
    • Upstream signals that toggle inhibitory autophosphorylation in vivo unknown
    • Structural basis of the autophosphorylation element not solved
  16. 2016 High

    Demonstrated mitochondrial and additional muscle-catabolic functions, placing p38beta inside mitochondria phosphorylating MnSOD and at the center of activin A-induced wasting.

    Evidence In vitro kinase and co-IP for MnSOD with T79A/S106A mutants and in vivo I/R models; muscle-specific p38beta knockout and isoform-specific siRNA for activin A catabolism

    PMID:27897407 PMID:27930699

    Open questions at the time
    • Import mechanism delivering p38beta to mitochondria not defined
    • Activin A-to-p38beta activation steps incompletely mapped
  17. 2017 High

    Extended p38beta into neurological disease and neuromodulatory signaling, showing it modulates mutant huntingtin levels and drives microglial beta-endorphin via PKA-p38beta-CREB.

    Evidence MAPK11 knockout in HD knockin mice with kinase-dead controls and behavioral rescue; isoform-specific siRNA with cAMP, phospho-cascade, POMC ELISA and intrathecal behavioral assays

    PMID:28202578 PMID:29151587

    Open questions at the time
    • Direct substrate linking p38beta to mHTT stability not identified
    • Whether CREB is a direct p38beta substrate in this cascade not shown
  18. 2020 High

    Completed the multi-arm model of cachexia by adding p300 Ser-12 phosphorylation and ULK1-dependent autophagy, and provided a druggable handle via preferential p38beta inhibition.

    Evidence Genetic knockdown, p300 phosphorylation and C/EBPbeta acetylation assays, muscle-specific knockout, ULK1 S555 phosphorylation and co-IP, nilotinib treatment with survival analysis

    PMID:31225455 PMID:33355181

    Open questions at the time
    • Relative contribution of UPP versus autophagy arms not quantified
    • Off-target effects of nilotinib not fully excluded
  19. 2021 High

    Identified a stress-responsive substrate controlling membrane trafficking, showing p38 phosphorylation of SNX27 Ser51 reshapes cargo binding to inhibit endocytic recycling.

    Evidence Phosphoproteomics, in vitro kinase assay, SNX27 S51 mutagenesis, cargo-binding and recycling assays across multiple stressors

    PMID:33605979

    Open questions at the time
    • Relative roles of p38alpha versus p38beta on SNX27 not separated
    • Physiological receptor cargoes most affected not enumerated
  20. 2023 Medium

    Implicated MAPK11 in viral and oncogenic contexts, defining it as a SARS-CoV-2 host dependency factor and a RUNX2-stabilizing partner in renal carcinoma.

    Evidence Genetic screening with multi-omics for SARS-CoV-2; co-IP and cycloheximide-chase RUNX2 stability assays with proliferation/migration readouts in ccRCC

    PMID:37345956 PMID:37525479

    Open questions at the time
    • SARS-CoV-2 substrates remain putative without individual biochemical validation
    • Direct phosphorylation underlying RUNX2 stabilization not demonstrated

Open questions

Synthesis pass · forward-looking unresolved questions
  • How distinct upstream stimuli select among p38beta's many substrates and subcellular pools (nuclear-excluded cytosol, mitochondria, endosomes) to produce divergent pro-survival, catabolic, and trafficking outcomes remains unresolved.
  • No unifying model linking stimulus identity to substrate selection
  • Mechanism targeting p38beta to mitochondria and other compartments undefined
  • Structural basis of substrate discrimination versus p38alpha not solved

Mechanism profile

Synthesis pass · controlled-vocabulary classification · explore literature graph →
Molecular activity
GO:0140096 catalytic activity, acting on a protein 8 GO:0016740 transferase activity 6 GO:0140110 transcription regulator activity 3
Localization
GO:0005829 cytosol 3 GO:0005634 nucleus 2 GO:0005739 mitochondrion 1
Pathway
R-HSA-162582 Signal Transduction 5 R-HSA-74160 Gene expression (Transcription) 4 R-HSA-8953897 Cellular responses to stimuli 4 R-HSA-1266738 Developmental Biology 2 R-HSA-9612973 Autophagy 1
Partners
ILKMAP2K6PRAKRAPTORSNX27SOD2STIM1ULK1

Evidence

Reading pass · 48 per-paper findings extracted from the source corpus
Year Finding Method Journal Conf PMIDs
1996 MAPK11 (p38beta) is a MAP kinase containing a TGY dual phosphorylation site required for kinase activity; it is preferentially activated by MKK6 (rather than MKK3/MKK4), and shows strong substrate preference for ATF2 (~20-fold greater transactivation than p38alpha), with kinetic studies showing ~180-fold greater activity than p38 on ATF2. In vitro kinase assays, in vivo transfection, two-dimensional phosphopeptide analysis, reporter gene assays, site-directed mutagenesis of TGY motif The Journal of biological chemistry High 8663524
1997 MAPK11 (p38-2/p38beta) is activated by stress signals and proinflammatory cytokines; MEK6 is its preferred upstream kinase; it phosphorylates ATF2 and Sap-1a but not Elk1 with increased transcriptional activity; steady-state kinetics suggest a sequential kinetic mechanism. In vitro kinase assays, steady-state kinetic analysis, two-dimensional phosphopeptide analysis, reporter gene assays The Journal of biological chemistry High 9235954
1998 MAPK11/SAPK2/p38 directly activates MSK1 in vitro; stress-induced activation of MSK1 in cells is blocked by SB203580 (a SAPK2/p38 inhibitor); MSK1 phosphorylates CREB at Ser133, suggesting SAPK2/p38 mediates stress-induced CREB activation via MSK1. In vitro kinase assay, pharmacological inhibition (SB203580), cell-based kinase activation assays The EMBO journal High 9687510
1998 MAPK11 (p38-2) is required for bradykinin-induced slow inhibition of N-type calcium current in NG108-15 cells; BK selectively activates p38-2, and SB203580 suppresses this inhibition, placing p38-2 downstream of G13 and Rac1/Cdc42 in this pathway. Electrophysiology, pharmacological inhibition (SB203580), kinase activity assays The Journal of neuroscience Medium 9412491
1998 Expression of p38beta attenuates SB202190-induced apoptosis and cell death induced by Fas ligation and UV irradiation, whereas p38alpha expression mildly induces cell death; SB202190 induces apoptosis through CPP32-like caspases, and this is blocked by p38beta overexpression, indicating p38beta and p38alpha have opposing roles in apoptosis. Overexpression of p38 isoforms, caspase activity assays, nuclear condensation and DNA fragmentation assays, Bcl-2 overexpression rescue The Journal of biological chemistry Medium 9632706
1998 SAPK2/p38 (including MAPK11) mediates oxidative stress-induced actin cytoskeletal reorganization into stress fibers and focal adhesion formation in endothelial cells via phosphorylation of HSP27 through MAPKAP kinase-2/3; SAPK2 inhibition by SB203580 blocks membrane blebbing during H2O2-induced apoptosis; expression of non-phosphorylatable HSP27 prevents F-actin accumulation and blebbing. Pharmacological inhibition (SB203580, PD098059), expression of mutant HSP27, F-actin staining, caspase assay, DNA fragmentation The Journal of cell biology High 9832563
1999 SAPK2/p38 pathway activation mediates oxidant-induced inhibition of insulin-stimulated glucose transport in skeletal muscle cells; inhibiting p38 with SB202190 or SB203580 restores insulin-stimulated glucose transport but not glycogen synthesis, establishing p38 as a cross-talk node between stress and insulin signaling. Glucose transport assay, glycogen synthesis assay, in vitro kinase assays, pharmacological inhibition (SB202190, SB203580, wortmannin, PD98059) The Journal of biological chemistry Medium 10593919
1999 SAPK2/p38 controls actin dynamics by phosphorylating HSP27 via MAPKAP kinase-2/3; this pathway mediates VEGF-induced actin reorganization and cell migration in vascular endothelial cells. Pharmacological inhibition, phosphorylation assays, cell migration assays Biochemical Society symposium Medium 10207622
1999 A short-lived protein upstream of SAPK2/p38 constitutes a heat-shock-specific sensing mechanism; cycloheximide progressively desensitizes cells to heat-shock-induced SAPK2/p38 activation, and MG132 (proteasome inhibitor) constitutively activates SAPK2/p38, suggesting proteasomal degradation controls this upstream activator. Pharmacological treatments (cycloheximide, MG132, SB203580), kinase activity assays, heat shock desensitization experiments The Journal of biological chemistry Medium 10608813
2000 VEGFR2-mediated SAPK2/p38 activation drives actin polymerization and cell migration in endothelial cells; VEGFR2 (not VEGFR1) is specifically responsible for SAPK2/p38 activation; the pathway is independent of FAK phosphorylation, which instead depends on HSP90. VEGFR1/VEGFR2-selective cell lines, neutralizing antibody, pharmacological inhibition (SB203580, geldanamycin), HSP90 overexpression rescue, migration assays The Journal of biological chemistry High 10744763
2000 p38alpha and p38beta are constitutively active in adult mouse brain; p38alpha localizes to dendrites and cytoplasmic/nuclear regions of neurons, whereas p38beta is preferentially localized to the nucleus of neurons. Biochemical fractionation, immunohistochemistry, in vivo kinase activity assays Journal of neuroscience research Medium 10820433
2000 Cyclic mechanical stretch of bladder smooth muscle cells activates p38 SAPK2 and JNK/SAPK pathways independently of ERK-MAPK; p38 SAPK2 pathway contributes to stretch-stimulated DNA synthesis and HB-EGF gene expression, independently of ErbB2 and AT1 receptor pathways. Pharmacological inhibition (SB203580, PD98059), kinase activity assays, DNA synthesis measurement, gene expression analysis American journal of physiology. Cell physiology Medium 11003596
2001 Tumor cell adhesion to E-selectin-expressing endothelium activates SAPK2/p38 in HT-29 tumor cells, leading to HSP27 phosphorylation and transendothelial migration; blocking SAPK2/p38 with SB203580 or dominant-negative SAPK2/p38 inhibits transendothelial migration but not cell adhesion. Dominant-negative MAPK11 expression, pharmacological inhibition (SB203580), phospho-HSP27 western blot, transendothelial migration assays The Journal of biological chemistry High 11448946
2001 p38beta (but not p38alpha) protects rat mesangial cells from TNF-alpha-induced apoptosis; p38beta does not affect TNF-alpha-induced NF-kappaB nuclear translocation. Adenovirus-mediated gene transfer of p38beta/dominant-negative p38beta, cell viability assay, NF-kappaB translocation assay, pharmacological inhibition (SB203580) Journal of cellular biochemistry Medium 11500933
2003 SAPK2/p38 mediates gap junction closure in astrocytes in response to IL-1beta and hyperosmotic stress; upon activation, p38/SAPK2 translocates from nucleus to cytoplasm; p38 inhibition with SB203580 reverses inhibition of gap junction communication; PKC acts as a distal effector of p38 in this pathway. Pharmacological inhibition (SB203580), immunocytochemistry for p38 localization, dye coupling assay, PKC inhibitor experiments Glia Medium 15048855
2004 VEGFR2 phosphorylation at Tyr1214 is required for VEGF-induced activation of Cdc42 and subsequently SAPK2/p38 and MAPKAP kinase-2, leading to actin remodeling into stress fibers; dominant-negative Cdc42 inhibits SAPK2/p38 activation; RhoA and Rac are not involved in SAPK2/p38-mediated actin reorganization. Site-directed mutagenesis of VEGFR2 Y1214F, dominant-negative/constitutively active Cdc42 constructs, GTPase activity assay, pharmacological inhibition (SB203580), actin staining Oncogene High 14724572
2004 SAPK2b/p38beta (MAPK11) specifically binds and phosphorylates glycogen synthase at Ser644, Ser652, Thr718 and Ser724 in vitro; p38beta serves as a priming kinase that enables GSK-3 to phosphorylate Ser640 and inhibit glycogen synthase activity; p38beta shows greater affinity for glycogen synthase than p38alpha, p38gamma, or p38delta. In vitro kinase assay, substrate binding assay, phosphopeptide mapping, isoform comparison, co-incubation with GSK-3 The Biochemical journal High 14680475
2004 p38alpha (but not p38beta) promotes Fas-mediated apoptosis by inhibiting phosphorylation and presence of c-FLIPS in DISC to promote caspase-8 activation; both p38alpha and p38beta contribute to mitochondrial Bax localization and inhibition of Bad phosphorylation. Overexpression and translational silencing of p38alpha/p38beta, DISC immunoprecipitation, FACS analysis, caspase activity, western blot Journal of cell science Medium 15572410
2005 p38beta (MAPK11) knockout mice are viable and show normal p38alpha activation, ERK1/2, JNK, MAPKAP-K2, and MSK1 activation, normal p38-dependent immediate-early gene transcription, normal T-cell development, and normal LPS-induced cytokine production; p38beta is dispensable for inflammatory disease progression in TNFDeltaARE mice, indicating p38alpha is the predominant isoform in immune responses. Genetic knockout, kinase activity assays, cytokine ELISA, TNFDeltaARE cross, disease scoring Molecular and cellular biology High 16287858
2005 Spinal p38beta (MAPK11) in microglia (not p38alpha in neurons) mediates tissue injury-induced hyperalgesia; intrathecal antisense knockdown of p38beta but not p38alpha prevents formalin-evoked nocifensive behavior and substance P-induced hyperalgesia, and blocks spinal p38 phosphorylation. Isoform-specific antisense oligonucleotides, behavioral pain assays (formalin, substance P), immunohistochemistry for isoform localization, phospho-p38 western blot Journal of neurochemistry High 15748168
2005 p38beta MAPK (MAPK11) mediates CO-induced caveolin-1 expression in smooth muscle cells; p38beta-/- fibroblasts fail to upregulate caveolin-1 in response to CO; p38beta downregulates ERK1/2, which represses caveolin-1 transcription; caveolin-1 is required for the antiproliferative effect of CO. p38beta knockout cells, p38beta gene transfer rescue, CO treatment, ERK1/2 western blot, caveolin-1 expression, cell proliferation assay Proceedings of the National Academy of Sciences of the United States of America High 16051704
2005 MAPK11/14 (p38 MAPK) activation is required for EGF-stimulated cytotrophoblast differentiation and syncytium formation; pharmacological inhibition (SB203580/SB202190) blocks spontaneous and EGF-stimulated beta-hCG secretion and cytotrophoblast fusion. Pharmacological inhibition (SB203580, SB202190), beta-hCG ELISA, BrdU proliferation assay, villous explant culture Biology of reproduction Medium 16120828
2006 Phosphorylation of VEGFR-2 at Tyr1214 recruits adapter Nck and Src-family kinase Fyn (but not c-Src) to VEGFR-2; Fyn activates PAK-2 and is required for SAPK2/p38 but not FAK activation; this Fyn-Nck-PAK2 complex drives SAPK2/p38 activation, stress fiber formation, and endothelial cell migration. Immunoprecipitation with HA-tagged VEGFR-2 mutants, chemical and dominant-negative inhibitors of Fyn/c-Src, stress fiber staining, migration assays, PAK-2 phosphorylation assay The Journal of biological chemistry High 16966330
2006 p38beta MAPK is required for Ca2+-induced PKCdelta/eta-mediated E2F1 proteasomal degradation during keratinocyte differentiation; dominant-negative p38beta but not p38alpha blocks E2F1 downregulation in this context. Dominant-negative p38beta expression, pharmacological PKC inhibitors, western blot for E2F1, differentiation assays Oncogene Medium 16116476
2007 Chemical genetics demonstrates that specific inhibition of p38alpha (not p38beta) is necessary and sufficient for anti-inflammatory efficacy; p38beta knock-in (T106M) mice are resistant to pharmacological p38 inhibition of LPS-induced TNF production; p38beta knockout mice show normal inflammatory responses. Chemical genetics knock-in mice (T106M mutation), p38beta knockout mice, LPS challenge, collagen antibody-induced arthritis model, TNF ELISA The Journal of biological chemistry High 17855341
2008 p38alpha-PRAK complex localizes to the nucleus while p38beta-PRAK complex localizes exclusively to the cytosol; two residues (Asp145/Leu156 in p38alpha vs. Gly145/Val156 in p38beta) determine the distinct localization; nuclear import (not export) is the determining step; Leu156 of p38alpha interacts with the NLS of PRAK; nuclear localization of PRAK is required for its antiproliferative function. Chimeric and point mutants of p38alpha/p38beta, subcellular fractionation, random mutagenesis, nuclear import assays, co-localization, NIH3T3 proliferation assay The Journal of biological chemistry High 18268017
2008 TGFbeta-induced alpha-smooth muscle cell actin (alphaSMA) expression in renal proximal tubular cells requires p38beta (not p38alpha) MAPK and is mediated via MKK6 (not MKK3); dominant-negative p38beta and dominant-negative MKK6b block TGFbeta-induced alphaSMA; Smad7 and dominant-negative Smad3 also block this effect. Adenoviral expression of dominant-negative p38alpha/p38beta and dominant-negative MKK3/MKK6, western blot for alphaSMA, alphaSMA promoter-luciferase reporter, phospho-specific antibodies Nephrology, dialysis, transplantation Medium 18192325
2009 The crystal structure of human p38beta was determined at 2.05 Å resolution; structural comparison with p38alpha revealed that differences in relative orientation of N- and C-terminal domains reduce the size of the ATP-binding pocket in p38beta compared to p38alpha. X-ray crystallography (PDB: 3gc8, 3gc9 for p38beta C162S and C119S/C162S mutants; 3gc7 for p38alpha C162S) Acta crystallographica. Section D, Biological crystallography High 19622861
2010 During hypoxia/reoxygenation in cardiomyocytes, p38alpha phosphorylates p53 at Ser15 leading to mitochondrial p53 translocation and apoptosis; p53 in turn suppresses p38beta activity; estrogen inhibits this p38alpha-p53 axis and preserves p38beta pro-survival activity. Pharmacological inhibition of p38alpha/p38beta, p53 inhibition, ROS measurement, cardiomyocyte apoptosis assays, western blot for phospho-p53, mitochondrial fractionation Cardiovascular research Medium 20724307
2011 p38alpha and p38beta together are required for mouse embryonic development; combined deletion causes cardiovascular abnormalities at midgestation absent in single knockouts; p38beta cannot fully substitute for p38alpha functions during embryogenesis (assessed by knock-in of p38beta under p38alpha promoter). Double knockout mice, p38beta knock-in under p38alpha promoter, embryonic phenotype analysis, cardiac gene expression analysis Proceedings of the National Academy of Sciences of the United States of America High 21768366
2011 p38beta (MAPK11) promotes phosphorylation of Raptor at Ser863 and Ser771 upon arsenite treatment, thereby activating mTORC1; arsenite induces direct interaction between p38beta and Raptor; this pathway is specific to arsenite and not activated by insulin, nutrients, anisomycin, or H2O2. Co-immunoprecipitation, in vitro kinase assay, phospho-Raptor western blot, mTORC1 activity assays, stimulus specificity comparison The Journal of biological chemistry High 21757713
2011 p38beta activity and STAT pathway are concurrently activated by neuropoietic cytokines (CNTF/LIF) in sympathetic neurons; p38beta overexpression in absence of cytokines stimulates cholinergic marker expression; p38beta-/- neurons show impaired neurotransmitter switch in vitro; stellate ganglion of p38beta-/- mice shows loss of cholinergic properties in vivo. p38beta knockout neurons, p38alpha/p38beta overexpression, dominant-negative p38, cytokine treatment, cholinergic marker expression, in vivo stellate ganglion analysis The Journal of neuroscience High 21865449
2012 p38beta (MAPK11) specifically phosphorylates C/EBPβ at Thr-188 (a site not phosphorylated by p38alpha), enabling C/EBPβ binding to the atrogin1/MAFbx promoter and upregulating this ubiquitin ligase; C/EBPβ T188A mutant acts as dominant-negative inhibitor of atrogin1/MAFbx upregulation; p38beta-mediated muscle catabolism is abrogated in C/EBPβ-null mice. Tryptic phosphopeptide mapping, ChIP assay, site-directed mutagenesis of C/EBPβ T188A, siRNA knockdown, constitutively active p38alpha/beta expression, C/EBPβ knockout mice, in vivo muscle injection Skeletal muscle High 23046544
2012 TGF-beta1 activates p38alpha (proapoptotic) and shifts VEGF signaling from p38beta (prosurvival) to p38alpha in endothelial cells; gene silencing of p38alpha blocks TGF-beta1-induced apoptosis; downregulation of p38beta or p38gamma causes massive apoptosis. Gene silencing (siRNA) of p38 isoforms, apoptosis assays, isoform-specific phosphorylation analysis Molecular cancer research Medium 22454
2013 SOCE-induced AMPK (alpha1 isoform) activates p38beta MAPK, which directly phosphorylates STIM1 on serine residues, inhibiting SOCE (acting as an 'off switch'); knockdown of p38beta (but not other p38 isoforms) prevents PAR-1-mediated STIM1 phosphorylation and potentiates Ca2+ entry. siRNA knockdown of p38 isoforms and AMPKα1, STIM1 phosphorylation assay, Ca2+ entry measurements, permeability assays, AICAR treatment The Journal of biological chemistry High 23625915
2013 Integrin-linked kinase (ILK) selectively forms cytoplasmic complexes with p38beta (not other p38 isoforms); ILK knockdown reduces p38beta protein levels post-translationally via the 26S proteasome; ILK-p38beta signaling regulates Hsp27 phosphorylation, actin cytoskeletal organization, and Rac1-dependent bladder cancer cell migration. siRNA knockdown of ILK/p38beta, co-immunoprecipitation, bimolecular fluorescence complementation, proximity ligation assay, proteasome inhibitor rescue (MG132), Hsp27 phosphorylation, migration assay Oncogene High 23435415
2014 p38beta (MAPK11) possesses an intrinsic autophosphorylation activity; a 13-residue region comprising part of the alpha-G helix and MAPK insert triggers this activity; when inserted into p38alpha, this fragment renders it spontaneously active in vitro and in mammalian cells; an interaction between the N-terminus and C-terminal extension suppresses this autophosphorylation in vivo. In vitro autophosphorylation assay, chimeric construct generation, mammalian cell expression, mutagenesis The Journal of biological chemistry High 25006254
2014 p38beta-mediated p38 activity in breast cancer cells upregulates MCP-1 secretion, which activates osteoclast differentiation and bone resorption; shRNA knockdown of p38beta reduces osteoclast differentiation in vitro and bone destruction in SCID mouse models. shRNA knockdown of p38beta, conditioned media osteoclast differentiation assay, MCP-1 ELISA, SCID mouse bone metastasis model Biochimie Medium 25066918
2016 p38beta MAPK mediates activin A/ActRIIB-induced skeletal muscle catabolism via C/EBPβ activation; siRNA knockdown of p38beta (not p38alpha) abolishes activin A catabolic effects; muscle-specific p38beta knockout mice are protected from activin A-induced muscle catabolism in vivo. siRNA knockdown, muscle-specific p38beta knockout mice, C2C12 myotube atrophy assays, ubiquitin ligase expression, LC3-II western blot, p38 inhibitor (SB202190) Journal of cachexia, sarcopenia and muscle High 27897407
2016 p38beta in mitochondria of cardiomyocytes phosphorylates MnSOD at Thr79 and Ser106; estrogen promotes mitochondrial localization of active p38beta and augments MnSOD activity; point mutation of T79/S106 to alanine abolishes MnSOD antioxidant function; physical interaction between p38beta and MnSOD demonstrated by co-IP. In vitro kinase assay, co-immunoprecipitation, mitochondrial fractionation, point mutagenesis of MnSOD T79A/S106A, MnSOD activity assay, ROS measurement, in vivo I/R model in OVX and ER-null mice PloS one High 27930699
2016 p38beta MAPK self-regulates basal activity through autophosphorylation at multiple sites in its MAPK insert (T241, S261) in addition to the activating T180 site; T241 phosphorylation reduces autophosphorylation in trans; S261 phosphorylation reduces activity of T180-phosphorylated p38beta; T241 is phosphorylated in vivo in bone and muscle tissues and correlates with myogenic differentiation. In vitro autophosphorylation assay, mass spectrometry, site-directed mutagenesis, mammalian cell expression, tissue phosphorylation analysis Molecular and cellular biology High 26976637
2017 MAPK11 (p38beta) is a positive modulator of mutant huntingtin (mHTT) protein levels via its kinase activity; MAPK11 knockout significantly rescues disease-relevant behavioral phenotypes in a knockin HD mouse model; the effect is mHTT-dependent, suggesting a feedback mechanism. MAPK11 knockout mice (HD knockin background), cell-based mHTT level assays, kinase-dead mutant, behavioral phenotyping Cell research High 29151587
2017 p38beta (MAPK11) mediates GLP-1R agonist exenatide-induced microglial POMC/beta-endorphin expression via a PKA-p38beta-CREB signaling cascade; siRNA knockdown of p38beta (not p38alpha) abolishes exenatide-induced p38 phosphorylation and POMC expression; intrathecal siRNA/p38beta blocks exenatide-induced spinal beta-endorphin expression and mechanical antiallodynia. siRNA isoform-specific knockdown (p38alpha vs. p38beta), intracellular cAMP assay, western blot for p-PKA/p-p38/p-CREB, POMC/beta-endorphin ELISA, intrathecal injection in neuropathic rats Molecular pharmacology High 28202578
2018 p38beta MAPK (MAPK11) mediates ULK1-dependent autophagy activation in cachectic skeletal muscle of tumor-bearing mice; p38beta activates transcription factor C/EBPβ to upregulate LC3b and Gabarapl1; p38beta phosphorylates ULK1 at S555; active ULK1 forms a complex with p38beta in myocytes; muscle-specific p38beta knockout abrogates tumor-induced autophagy, UPP activation, and muscle wasting. Muscle-specific p38beta knockout mice, LLC tumor model, ULK1 phosphorylation assays, co-immunoprecipitation (ULK1-p38beta complex), C/EBPβ activation assays, autophagy markers (LC3b, Gabarapl1), p38alpha pharmacological comparison Cell stress High 31225455
2020 Upon cancer-induced TLR4 activation in skeletal muscle, p38beta MAPK phosphorylates Ser-12 on p300, stimulating C/EBPβ acetylation and muscle wasting; nilotinib preferentially inhibits p38beta over p38alpha and abrogates this pathway; systemic nilotinib at 0.5 mg/kg/day alleviates muscle wasting and prolongs survival in tumor-bearing mice. Genetic knockdown, p300 phosphorylation assay, C/EBPβ acetylation assay, catabolic gene expression, tumor-bearing mouse model, nilotinib treatment, survival analysis Cancer research High 33355181
2021 MAPK11/14 (p38 MAPK) directly phosphorylates SNX27 at Ser51 in response to multiple stressors (starvation, LPS, IL-6, EGF), altering its cargo-binding pocket conformation and reducing interactions with cargo proteins, thereby inhibiting endocytic recycling and promoting receptor lysosomal degradation. Phosphoproteomics, in vitro kinase assay, mutagenesis of SNX27 S51, cargo binding assays, endocytic recycling assays, multiple stress stimuli The Journal of cell biology High 33605979
2023 p38beta (MAPK11) is a critical host factor for SARS-CoV-2 replication, functioning at a step after viral mRNA expression; genetic screening, proteomics, and phosphoproteomics identified putative host and viral p38beta substrates in SARS-CoV-2-infected cells; most identified host p38beta substrates have intrinsic antiviral activities. Quantitative genetic screening, genomics, proteomics, phosphoproteomics, multiple cell line validation mBio Medium 37345956
2023 Phosphorylated MAPK11 (p38beta) physically interacts with RUNX2 and sustains RUNX2 protein stability in clear cell renal cell carcinoma cells; P-MAPK11 and RUNX2 co-immunoprecipitate; high RUNX2 expression can neutralize functional degradation of MAPK11; both promote ccRCC cell proliferation and migration. Co-immunoprecipitation, cycloheximide chase assay (RUNX2 half-life), siRNA knockdown, colony formation, EdU assay, transwell migration Journal of cellular and molecular medicine Medium 37525479

Source papers

Stage 0 corpus · 100 papers · ranked by NIH iCite citations
Year Title Journal Citations PMID
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 845 9687510
1996 Characterization of the structure and function of a new mitogen-activated protein kinase (p38beta). The Journal of biological chemistry 642 8663524
1997 Activation of stress-activated protein kinase-3 (SAPK3) by cytokines and cellular stresses is mediated via SAPKK3 (MKK6); comparison of the specificities of SAPK3 and SAPK2 (RK/p38). The EMBO journal 327 9029150
1998 SAPK2/p38-dependent F-actin reorganization regulates early membrane blebbing during stress-induced apoptosis. The Journal of cell biology 262 9832563
2000 Vascular endothelial growth factor (VEGF)-driven actin-based motility is mediated by VEGFR2 and requires concerted activation of stress-activated protein kinase 2 (SAPK2/p38) and geldanamycin-sensitive phosphorylation of focal adhesion kinase. The Journal of biological chemistry 258 10744763
1998 Induction of apoptosis by SB202190 through inhibition of p38beta mitogen-activated protein kinase. The Journal of biological chemistry 244 9632706
2005 Generation and characterization of p38beta (MAPK11) gene-targeted mice. Molecular and cellular biology 197 16287858
2004 Phosphorylation of tyrosine 1214 on VEGFR2 is required for VEGF-induced activation of Cdc42 upstream of SAPK2/p38. Oncogene 174 14724572
1999 Regulation of glucose transport and glycogen synthesis in L6 muscle cells during oxidative stress. Evidence for cross-talk between the insulin and SAPK2/p38 mitogen-activated protein kinase signaling pathways. The Journal of biological chemistry 152 10593919
1997 p38-2, a novel mitogen-activated protein kinase with distinct properties. The Journal of biological chemistry 148 9235954
2006 Phosphorylation of Tyr1214 within VEGFR-2 triggers the recruitment of Nck and activation of Fyn leading to SAPK2/p38 activation and endothelial cell migration in response to VEGF. The Journal of biological chemistry 134 16966330
2005 Spinal p38beta isoform mediates tissue injury-induced hyperalgesia and spinal sensitization. Journal of neurochemistry 118 15748168
2019 Circ_0001955 facilitates hepatocellular carcinoma (HCC) tumorigenesis by sponging miR-516a-5p to release TRAF6 and MAPK11. Cell death & disease 107 31822654
2005 Caveolin-1 expression by means of p38beta mitogen-activated protein kinase mediates the antiproliferative effect of carbon monoxide. Proceedings of the National Academy of Sciences of the United States of America 100 16051704
2003 Integrin alphavbeta3, requirement for VEGFR2-mediated activation of SAPK2/p38 and for Hsp90-dependent phosphorylation of focal adhesion kinase in endothelial cells activated by VEGF. Cell stress & chaperones 98 12820653
2001 Transendothelial migration of colon carcinoma cells requires expression of E-selectin by endothelial cells and activation of stress-activated protein kinase-2 (SAPK2/p38) in the tumor cells. The Journal of biological chemistry 97 11448946
1999 Regulation of actin dynamics by stress-activated protein kinase 2 (SAPK2)-dependent phosphorylation of heat-shock protein of 27 kDa (Hsp27). Biochemical Society symposium 89 10207622
2014 Activation of the MAPK11/12/13/14 (p38 MAPK) pathway regulates the transcription of autophagy genes in response to oxidative stress induced by a novel copper complex in HeLa cells. Autophagy 88 24905917
2016 Activin A induces skeletal muscle catabolism via p38β mitogen-activated protein kinase. Journal of cachexia, sarcopenia and muscle 78 27897407
2001 The Epstein-Barr virus latent membrane protein 1 induces interleukin-10 in Burkitt's lymphoma cells but not in Hodgkin's cells involving the p38/SAPK2 pathway. Virology 77 11162833
2010 Oestrogen prevents cardiomyocyte apoptosis by suppressing p38α-mediated activation of p53 and by down-regulating p53 inhibition on p38β. Cardiovascular research 76 20724307
2000 Cyclic stretch activates p38 SAPK2-, ErbB2-, and AT1-dependent signaling in bladder smooth muscle cells. American journal of physiology. Cell physiology 70 11003596
2007 Chemical genetics define the roles of p38alpha and p38beta in acute and chronic inflammation. The Journal of biological chemistry 69 17855341
2017 Intrathecal administration of antisense oligonucleotide against p38α but not p38β MAP kinase isoform reduces neuropathic and postoperative pain and TLR4-induced pain in male mice. Brain, behavior, and immunity 63 29128611
2020 Optimal linker length for small molecule PROTACs that selectively target p38α and p38β for degradation. European journal of medicinal chemistry 62 32634680
2012 TGF-β1 induces endothelial cell apoptosis by shifting VEGF activation of p38(MAPK) from the prosurvival p38β to proapoptotic p38α. Molecular cancer research : MCR 62 22522454
2000 Constitutive activity and differential localization of p38alpha and p38beta MAPKs in adult mouse brain. Journal of neuroscience research 61 10820433
2006 Diazoxide prevents diabetes through inhibiting pancreatic beta-cells from apoptosis via Bcl-2/Bax rate and p38-beta mitogen-activated protein kinase. Endocrinology 60 17053028
2018 The sucrose non-fermenting-1-related protein kinases SAPK1 and SAPK2 function collaboratively as positive regulators of salt stress tolerance in rice. BMC plant biology 59 30236054
2008 Transforming growth factor-beta-induced alpha-smooth muscle cell actin expression in renal proximal tubular cells is regulated by p38beta mitogen-activated protein kinase, extracellular signal-regulated protein kinase1,2 and the Smad signalling during epithelial-myofibroblast transdifferentiation. Nephrology, dialysis, transplantation : official publication of the European Dialysis and Transplant Association - European Renal Association 57 18192325
2005 Epidermal growth factor stimulation of trophoblast differentiation requires MAPK11/14 (p38 MAP kinase) activation. Biology of reproduction 57 16120828
2012 p38β MAPK upregulates atrogin1/MAFbx by specific phosphorylation of C/EBPβ. Skeletal muscle 53 23046544
2011 Phosphorylation of Raptor by p38beta participates in arsenite-induced mammalian target of rapamycin complex 1 (mTORC1) activation. The Journal of biological chemistry 53 21757713
1999 Activation of the neutrophil NADPH oxidase is inhibited by SB 203580, a specific inhibitor of SAPK2/p38. Biochemical and biophysical research communications 53 10362531
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
2017 Both classic Gs-cAMP/PKA/CREB and alternative Gs-cAMP/PKA/p38β/CREB signal pathways mediate exenatide-stimulated expression of M2 microglial markers. Journal of neuroimmunology 48 29249556
2013 Thymoquinone induces apoptosis in oral cancer cells through p38β inhibition. The American journal of Chinese medicine 48 23711149
2013 Store-operated Ca2+ entry (SOCE) induced by protease-activated receptor-1 mediates STIM1 protein phosphorylation to inhibit SOCE in endothelial cells through AMP-activated protein kinase and p38β mitogen-activated protein kinase. The Journal of biological chemistry 43 23625915
2004 Identification of glycogen synthase as a new substrate for stress-activated protein kinase 2b/p38beta. The Biochemical journal 43 14680475
2017 Cynandione A attenuates neuropathic pain through p38β MAPK-mediated spinal microglial expression of β-endorphin. Brain, behavior, and immunity 42 28189715
2004 p38/SAPK2 controls gap junction closure in astrocytes. Glia 41 15048855
2008 Efficient adult skeletal muscle regeneration in mice deficient in p38beta, p38gamma and p38delta MAP kinases. Cell cycle (Georgetown, Tex.) 39 18641461
2004 p38alpha, but not p38beta, inhibits the phosphorylation and presence of c-FLIPS in DISC to potentiate Fas-mediated caspase-8 activation and type I apoptotic signaling. Journal of cell science 38 15572410
2018 p38β MAPK mediates ULK1-dependent induction of autophagy in skeletal muscle of tumor-bearing mice. Cell stress 37 31225455
1998 The mitogen-activated protein kinase p38-2 is necessary for the inhibition of N-type calcium current by bradykinin. The Journal of neuroscience : the official journal of the Society for Neuroscience 37 9412491
2021 Phosphorylation of SNX27 by MAPK11/14 links cellular stress-signaling pathways with endocytic recycling. The Journal of cell biology 36 33605979
2017 Suppression of MAPK11 or HIPK3 reduces mutant Huntingtin levels in Huntington's disease models. Cell research 36 29151587
2014 Inhibition of neuronal p38α, but not p38β MAPK, provides neuroprotection against three different neurotoxic insults. Journal of molecular neuroscience : MN 36 25012593
2014 The p38β mitogen-activated protein kinase possesses an intrinsic autophosphorylation activity, generated by a short region composed of the α-G helix and MAPK insert. The Journal of biological chemistry 35 25006254
2017 p38β Mitogen-Activated Protein Kinase Signaling Mediates Exenatide-Stimulated Microglial β-Endorphin Expression. Molecular pharmacology 34 28202578
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
2004 Nerve growth factor pretreatment attenuates oxygen and glucose deprivation-induced c-Jun amino-terminal kinase 1 and stress-activated kinases p38alpha and p38beta activation and confers neuroprotection in the pheochromocytoma PC12 Model. Journal of molecular neuroscience : MN 34 14997018
2009 The three-dimensional structure of MAP kinase p38beta: different features of the ATP-binding site in p38beta compared with p38alpha. Acta crystallographica. Section D, Biological crystallography 33 19622861
2016 Estrogen Protects the Female Heart from Ischemia/Reperfusion Injury through Manganese Superoxide Dismutase Phosphorylation by Mitochondrial p38β at Threonine 79 and Serine 106. PloS one 32 27930699
2005 JNK/SAPK and p38 SAPK-2 mediate mechanical stretch-induced apoptosis via caspase-3 and -9 in NRK-52E renal epithelial cells. Nephron. Experimental nephrology 32 16179830
2021 MAPK11 regulates seed germination and ABA signaling in tomato by phosphorylating SnRKs. Journal of experimental botany 30 33448300
2001 p38beta MAP kinase protects rat mesangial cells from TNF-alpha-induced apoptosis. Journal of cellular biochemistry 30 11500933
2020 Cancer-Induced Muscle Wasting Requires p38β MAPK Activation of p300. Cancer research 29 33355181
2008 Determinants that control the distinct subcellular localization of p38alpha-PRAK and p38beta-PRAK complexes. The Journal of biological chemistry 29 18268017
2006 E2F1 stability is regulated by a novel-PKC/p38beta MAP kinase signaling pathway during keratinocyte differentiation. Oncogene 29 16116476
2003 Synthetic anisomycin analogues activating the JNK/SAPK1 and p38/SAPK2 pathways. Organic & biomolecular chemistry 29 14737674
2013 Selective regulation of p38β protein and signaling by integrin-linked kinase mediates bladder cancer cell migration. Oncogene 28 23435415
2020 TRIM67 inhibits tumor proliferation and metastasis by mediating MAPK11 in Colorectal Cancer. Journal of Cancer 26 32922543
2015 The problem of pyridinyl imidazole class inhibitors of MAPK14/p38α and MAPK11/p38β in autophagy research. Autophagy 26 26061537
2014 MAPK11 in breast cancer cells enhances osteoclastogenesis and bone resorption. Biochimie 26 25066918
2014 Mitochondrial p38β and manganese superoxide dismutase interaction mediated by estrogen in cardiomyocytes. PloS one 25 24465521
2000 The mitogen-activated protein kinase p38 pathway is conserved in metazoans: cloning and activation of p38 of the SAPK2 subfamily from the sponge Suberites domuncula. Biology of the cell 25 10879630
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
2009 Isoflavone genistein protects human vascular endothelial cells against tumor necrosis factor-alpha-induced apoptosis through the p38beta mitogen-activated protein kinase. Apoptosis : an international journal on programmed cell death 23 19082897
2020 p38β and Cancer: The Beginning of the Road. International journal of molecular sciences 22 33053909
2023 SARS-CoV-2 hijacks p38β/MAPK11 to promote virus replication. mBio 21 37345956
2021 p38β - MAPK11 and its role in female cancers. Journal of ovarian research 21 34174910
2020 MYB57 transcriptionally regulates MAPK11 to interact with PAL2;3 and modulate rice allelopathy. Journal of experimental botany 21 31811717
2022 miR-143-Mediated Responses to Betaine Supplement Repress Lipogenesis and Hepatic Gluconeogenesis by Targeting MAT1a and MAPK11. Journal of agricultural and food chemistry 20 35734958
2018 Diagnostic Significance of p38 Isoforms (p38α, p38β, p38γ, p38δ) in Head and Neck Squamous Cell Carcinoma: Comparative Serum Level Evaluation and Design of Novel Peptide Inhibitor Targeting the Same. Cancer research and treatment 20 29747487
2011 p38β MAPK affords cytoprotection against oxidative stress-induced astrocyte apoptosis via induction of αB-crystallin and its anti-apoptotic function. Neuroscience letters 20 21777656
2011 Inhibition of SAPK2/p38 enhances sensitivity to mTORC1 inhibition by blocking IRES-mediated translation initiation in glioblastoma. Molecular cancer therapeutics 20 21911485
2020 SAPK2 contributes to rice yield by modulating nitrogen metabolic processes under reproductive stage drought stress. Rice (New York, N.Y.) 18 32514747
2019 Knocking down of LINC01220 inhibits proliferation and induces apoptosis of endometrial carcinoma through silencing MAPK11. Bioscience reports 18 31123170
2013 Deficiency in p38β MAPK fails to inhibit cytokine production or protect neurons against inflammatory insult in in vitro and in vivo mouse models. PloS one 17 23457629
2011 p38β-regulated induction of the heat shock response by carbon monoxide releasing molecule CORM-2 mediates cytoprotection in lung cells in vitro. European journal of pharmacology 17 21925493
2018 lncRNA ENSMUST00000134285 Increases MAPK11 Activity, Regulating Aging-Related Myocardial Apoptosis. The journals of gerontology. Series A, Biological sciences and medical sciences 15 29415197
2016 p38β Mitogen-Activated Protein Kinase Modulates Its Own Basal Activity by Autophosphorylation of the Activating Residue Thr180 and the Inhibitory Residues Thr241 and Ser261. Molecular and cellular biology 15 26976637
1999 A short lived protein involved in the heat shock sensing mechanism responsible for stress-activated protein kinase 2 (SAPK2/p38) activation. The Journal of biological chemistry 15 10608813
2015 Clinicopathological significance of p38β, p38γ, and p38δ and its biological roles in esophageal squamous cell carcinoma. Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine 13 26666822
2015 Coronin 1A depletion protects endothelial cells from TNFα-induced apoptosis by modulating p38β expression and activation. Cellular signalling 12 25936522
2012 p38β MAP kinase as a therapeutic target for pancreatic cancer. Chemical biology & drug design 12 22515544
2008 COX-2 promoter activation by AT1R-Gq-PAK-p38beta signaling in intestinal epithelial cells. Biochimica et biophysica acta 12 18515110
2019 Roles of p38α and p38β mitogen‑activated protein kinase isoforms in human malignant melanoma A375 cells. International journal of molecular medicine 11 31661126
2010 Interferon-alpha induces the growth inhibition of human T-cell leukaemia line Jurkat through p38alpha and p38beta. Journal of biochemistry 11 20053787
2003 Dynamic expression of p38beta MAPK in neurons and astrocytes after transient focal ischemia. Brain research 11 12763629
2014 Identification of p38β as a therapeutic target for the treatment of Sézary syndrome. The Journal of investigative dermatology 10 25148579
2013 p27 suppresses cyclooxygenase-2 expression by inhibiting p38β and p38δ-mediated CREB phosphorylation upon arsenite exposure. Biochimica et biophysica acta 10 23639288
2010 Activin A induction of erythroid differentiation through MKK6-p38alpha/p38beta pathway is inhibited by follistatin. Journal of cellular physiology 10 20162623
2023 Phosphorylated MAPK11 promotes the progression of clear cell renal cell carcinoma by maintaining RUNX2 protein abundance. Journal of cellular and molecular medicine 9 37525479
2013 p38β, A novel regulatory target of Pokemon in hepatic cells. International journal of molecular sciences 9 23807508
2020 p38β (MAPK11) mediates gemcitabine-associated radiosensitivity in sarcoma experimental models. Radiotherapy and oncology : journal of the European Society for Therapeutic Radiology and Oncology 8 33310004
2023 Anthracycline cardiotoxicity is exacerbated by global p38β genetic ablation in a sexually dimorphic manner but unaltered by cardiomyocyte-specific p38α loss. American journal of physiology. Heart and circulatory physiology 6 37624097
2021 Weight Loss in Cancer Patients Correlates With p38β MAPK Activation in Skeletal Muscle. Frontiers in cell and developmental biology 6 34950660
2021 The role of MAPK11/12/13/14 (p38 MAPK) protein in dopamine agonist-resistant prolactinomas. BMC endocrine disorders 5 34814904

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