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Protein Kinase CProtein KinasesCyclic AMP-Dependent Protein KinasesCalcium-Calmodulin-Dependent Protein KinasesProtein-Serine-Threonine KinasesMitogen-Activated Protein KinasesPhosphorylationMAP Kinase Signaling SystemProtein Kinase Inhibitorsp38 Mitogen-Activated Protein KinasesPhosphatidylinositol 3-KinasesEnzyme ActivationMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase KinasesProtein Kinase C-alphaMitogen-Activated Protein Kinase 3Signal TransductionProtein Kinase C-deltaJNK Mitogen-Activated Protein KinasesAMP-Activated Protein KinasesMolecular Sequence DataIsoenzymesTetradecanoylphorbol AcetateCells, CulturedAmino Acid SequenceProtein Kinase C-epsilonProtein Kinase C betasrc-Family KinasesCell LineMitogensProtein-Tyrosine KinasesCyclic GMP-Dependent Protein KinasesEnzyme InhibitorsCDC2 Protein KinaseKineticsCasein Kinase IICyclic AMPProtein BindingMAP Kinase Kinase KinasesPhosphoproteinsCalcium-Calmodulin-Dependent Protein Kinase Type 2TransfectionBlotting, WesterneIF-2 KinaseBase SequenceProto-Oncogene ProteinsMAP Kinase Kinase 1Extracellular Signal-Regulated MAP KinasesMutationp21-Activated KinasesSerineCyclin-Dependent KinasesRibosomal Protein S6 KinasesCalciumProto-Oncogene Proteins c-aktTumor Suppressor Protein p53RNA, MessengerRecombinant ProteinsCell DivisionMAP Kinase Kinase 4Casein KinasesSubstrate SpecificityApoptosisDiglyceridesPhorbol 12,13-DibutyrateBinding SitesTumor Cells, CulturedIntracellular Signaling Peptides and ProteinsPokeweed MitogensRecombinant Fusion ProteinsIsoquinolinesPhorbol EstersStaurosporine1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineMaleimidesGlycogen Synthase Kinase 3Gene Expression RegulationFlavonoidsProtein Structure, TertiaryCreatine KinaseTyrosineIndolesDNA-Activated Protein KinaseDose-Response Relationship, DrugSequence Homology, Amino AcidDNA-Binding ProteinsCell Line, Tumor3T3 CellsPhosphotransferases (Alcohol Group Acceptor)Carrier ProteinsCyclic AMP-Dependent Protein Kinase Type IITranscription, Genetic3-Phosphoinositide-Dependent Protein KinasesImmunoblottingTime FactorsPyruvate KinaseGene Expression Regulation, EnzymologicPrecipitin TestsCell Cycle ProteinsReceptor Protein-Tyrosine Kinases
MAPKInhibitorPhosphorylationMAPKsNeuronsPathwayInhibition of p38ApoptosisMRNAsPhosphorylatesRegulatesCytokinesInhibitorsMiceReceptorUbiquitouslyDegradationBindsInhibitsMutationsNonethelessPathwaysSequenceExpressionFoundDiseasesChemicalsPEPTIDERoleActivitySpecificResultsAlphaLevelHumanFunctionalDevelopmentProvideResponseComplex
MAPK13
  • For example, the mitogen-activated protein kinase (MAPK) p38 pathway mediates stabilization of tumor necrosis factor alpha (TNF-alpha) mRNA in myeloid cells stimulated with bacterial lipopolysaccharide (LPS). (ed.ac.uk)
  • We present evidence that phosphorylation of TTP is mediated by the p38-regulated kinase MAPKAPK2 (MAPK-activated protein kinase 2). (ed.ac.uk)
  • We measured on Northern gels the migration of reporter mRNAs isolated from cells transfected only with reporter plasmid or co-transfected with an active mutant of MAPK kinase-6, and treated either with or without the p38 MAPK inhibitor SB 203580. (ox.ac.uk)
  • p38 MAPK activation inhibited the deadenylation of reporter mRNAs containing either the cyclooxygenase-2 or tumor necrosis factor AREs. (ox.ac.uk)
  • The regulation of deadenylation by p38 MAPK was found to be specific because deadenylation of the beta-globin reporter mRNA either lacking an ARE or containing the c-Myc 3'-untranslated region (which is not p38 MAPK-responsive) was unaffected by p38 MAPK. (ox.ac.uk)
  • It was concluded that the p38 MAPK pathway predominantly regulates deadenylation, rather than decay of the mRNA body, and this provides an explanation for why p38 MAPK regulates mRNA stability in some situations and translation in others. (ox.ac.uk)
  • A variety of extrinsic cues converge on the extracellular signal-regulated kinase/mitogen activated protein kinase (ERK/MAPK) pathway. (nature.com)
  • Here we found that the germinal ablation of the MAPK c-Jun N-Terminal Kinase isoform 1 (JNK1) results in a significant reduction of myelin in the cerebral cortex and corpus callosum at both postnatal and adult stages. (nature.com)
  • The secretion of inflammatory factors as well as the marker proteins in the mitogen-activated protein kinase (MAPK) pathway were detected by Western blot. (frontiersin.org)
  • 2013 ). In myocardial injury models, inhibition of p38 MAPK decreased the infarction size (Ma et al. (frontiersin.org)
  • 2010 ). In addition, the p38 MAPK inhibitor effectively shortened the duration of seizures in epileptic rats (Yang et al. (frontiersin.org)
  • Here we demonstrate that p38 MAPK gamma (p38γ) acts as a CDK-like kinase and thus cooperates with CDKs, regulating entry into the cell cycle. (nature.com)
  • These findings imply a novel and unexpected role for p38 MAPK inhibition in myogenesis and highlight the importance of the limb bud microenvironment in promoting the progression of limb myoblasts. (biologists.com)
Inhibitor4
  • The human trabecular meshwork cells were treated with t BHP for 1 or 2 h with or without pretreatment of SB203580, an inhibitor of MAP kinase homologs. (molvis.org)
  • ASK1DeltaN-induced neurite outgrowth was strongly inhibited by treatment with the p38 inhibitor SB203580 but not with the MEK inhibitors, suggesting that activation of p38, rather than of ERK, is required for the neurite-inducing activity of ASK1 in PC12 cells. (nih.gov)
  • Lack of p38γ or treatment with the p38γ inhibitor pirfenidone protects against the chemically induced formation of liver tumours. (nature.com)
  • The small-molecule inhibitor IU1, specific for USP14 has previously been shown to activate AMPK in HC cells. (helsinki.fi)
Phosphorylation4
  • We also observed that ASK1DeltaN induced expression of several neuron-specific proteins and phosphorylation of neurofilament proteins, confirming that PC12 cells differentiated into mature neuronal cells by ASK1. (nih.gov)
  • In mouse hepatocytes, p38γ induces proliferation after partial hepatectomy by promoting the phosphorylation of retinoblastoma tumour suppressor protein at known CDK target residues. (nature.com)
  • The N-terminal phosphorylation of RB by p38 bypasses its inactivation by CDKs and prevents proliferation in cancer cells. (nature.com)
  • Western blotting was applied to investigate the protein phosphorylation level (i.e. activation) of AMPK. (helsinki.fi)
MAPKs6
  • Mitogen-activated protein kinases (MAPKs) comprise a large family of proteins activated by a wide range of proinflammatory cytokines and environmental stress. (molvis.org)
  • Among MAPKs, the c-Jun N-terminal kinases (JNKs) include three isoforms-JNK1, JNK2 and JNK3. (nature.com)
  • Mitogen-activated protein kinases (MAPKs) consist of a family of protein-serine/protein-threonine kinases followed by proline, prevalent in mammals (Pearson et al. (frontiersin.org)
  • Activated by stress, p38 MAPKs regulate vital cellular responses such as migration, contraction, cytokine production, and death in macrophages and myocardial and endothelial cells (Marber et al. (frontiersin.org)
  • The p38 Mitogen-activated Protein Kinases (MAPKs) are a family of four related Ser/Thr kinases activated by proinflammatory cytokines and environmental stresses. (rndsystems.com)
  • Signaling through the p38 mitogen-activated protein kinases (MAPKs) is essential for cartilage formation in primary cultures of limb mesenchyme. (biologists.com)
Neurons1
  • Philips and Felix [ 4 ] proved the presence of Ang II-activated neurons in the brain and subfornical organs [ 4 ]. (hindawi.com)
Pathway2
  • The p38 pathway is required for the induction of TNF-alpha RNA-binding activity and for the expression of TTP protein and mRNA. (ed.ac.uk)
  • Our findings demonstrate a direct link between a specific signal transduction pathway and a specific RNA-binding protein, both of which are known to regulate TNF-alpha gene expression at a posttranscriptional level. (ed.ac.uk)
Inhibition of p381
  • Here we show that, concurrent with a decrease in chondrogenesis, inhibition of p38 in limb bud cultures dramatically promotes muscle development. (biologists.com)
Apoptosis2
  • This study is to investigate the role of p38 mitogen-activated protein kinase (p38MAPK) in tert -butyl hydroperoxide ( t BHP)-induced apoptosis of human trabecular meshwork (iHTM) cells. (molvis.org)
  • Apoptosis signal-regulating kinase 1 (ASK1) is a ubiquitously expressed mitogen-activated protein kinase kinase kinase that activates the c-Jun N-terminal kinase (JNK) and p38 mitogen-activated protein kinase signaling cascades. (nih.gov)
MRNAs2
  • p38 Mitogen-activated protein kinase stabilizes mRNAs that contain cyclooxygenase-2 and tumor necrosis factor AU-rich elements by inhibiting deadenylation. (ox.ac.uk)
  • Microarray analysis was performed to screen aberrantly expressed mRNAs and activated signaling pathways between epileptic rats and normal controls. (frontiersin.org)
Phosphorylates3
  • Fig. 1: p38γ phosphorylates Rb and promotes liver proliferation after PHx. (nature.com)
  • Once activated, p38 phosphorylates a number of targets, including the nuclear transcription factors ATF2 and Max. (rndsystems.com)
  • Once activated, p38 alpha phosphorylates a number of targets, including the cytoplasmic kinases MNK 4 and PRAK5 and the nuclear transcription factors ATF2 1 and STAT1. (rndsystems.com)
Regulates3
  • The zinc finger protein tristetraprolin (TTP) is expressed in response to LPS and regulates the stability of TNF-alpha mRNA. (ed.ac.uk)
  • p38γ regulates the localisation of SAP97 in the cytoskeleton by modulating its interaction with GKAP. (nature.com)
  • Degradation of cellular proteins in the ubiquitin-proteasome system regulates various biological processes. (helsinki.fi)
Cytokines1
  • Peripheral lung inflammation may cause a "spill-over" of cytokines, such as interlukin (IL)-6, IL-1β and tumour necrosis factor (TNF)-α, into the systemic circulation, which may increase acute-phase proteins such as C-reactive protein (CRP). (ersjournals.com)
Inhibitors2
  • Specifically,treatment of primary limb bud cultures with p38 inhibitors increases the expression of myogenic markers and causes a striking increase in formation of myotubes, which were detected using antibodies specific for myosin heavy chain. (biologists.com)
  • We provide evidence for the maintenance and rapid organization of existing,somitic-derived limb myoblasts in response to p38 inhibitors. (biologists.com)
Mice2
  • Concurrent deletion of cyclin E1 and cyclin-dependent kinase 2 in hepatocytes inhibits DNA replication and liver regeneration in mice. (nature.com)
  • 2010 ). Results from cav-1 (caveolin-1, the key structural protein of caveolae)-deficient mice indicated that cav-1 in endothelium is essential in the translocation of LDL-derived cholesterol into the vessel wall and in the development of atherosclerosis, and this result was further confirmed in apoE-/- mice (Fernandez-Hernando et al. (springer.com)
Receptor4
  • The protein encoded by this gene is a receptor for C-C type chemokines. (cancerindex.org)
  • Resveratrol also down-regulated the increased expressions of vascular endothelial growth factor (VEGF) and kinase insert domain receptor (KDR, or VEGF receptor-2) induced by high glucose. (springer.com)
  • Current therapies for comorbid diseases, such as statins and peroxisome proliferator-activated receptor-agonists, may provide unexpected benefits for COPD patients. (ersjournals.com)
  • Intrinsic brain RAS is an enzyme-neuropeptide system having functional components (angiotensinogen, peptidases, angiotensin, and specific receptor proteins) with important biological and neurobiological activities in the brain. (hindawi.com)
Ubiquitously1
  • Ubiquitously expressed, p38 alpha is dually phosphorylated by MKK3 and MKK6 at Thr180 and Tyr182. (rndsystems.com)
Degradation1
  • p38γ and δ promote heart hypertrophy by targeting the mTOR-inhibitory protein DEPTOR for degradation. (nature.com)
Binds1
  • An immobilized capture antibody specific for p38 alpha binds both phosphorylated and unphosphorylated p38 alpha. (rndsystems.com)
Inhibits2
  • Fig. 4: Pirfenidone inhibits p38γ activity and protects against DEN-induced HCC. (nature.com)
  • By assessing the mitochondria respiration we found evidence proposing IU1 inhibits complex I. Our results suggests that IU1 activates AMPK in certain cell lines with the possible underlying mechanism being the inhibition of complex I of the respiratory chain. (helsinki.fi)
Mutations2
  • Scope includes mutations and abnormal protein expression. (cancerindex.org)
  • Our studies are focused on understanding how cartilage ECM proteins function, defining the mechanisms by which mutations in cartilage proteins cause chondrodysplasia, and understanding the mechanisms by which osteoarthritis develops. (manchester.ac.uk)
Nonetheless1
  • Nonetheless, the time course effects of prolonged post-exercise protein co-ingestion in enhancing the adaptive response to running-based endurance exercise training in adults remains to be established. (biomedcentral.com)
Pathways1
Sequence2
  • p38γ shares high sequence homology, inhibition sensitivity and substrate specificity with CDK family members. (nature.com)
  • All four p38 family members, alpha, beta, gamma, and delta, are phosphorylated by MKK3 and/or MKK6 at dual Thr and Tyr positions within the phosphoacceptor sequence Thr-Gly-Tyr. (rndsystems.com)
Expression3
  • We found that p38 and to a lesser extent JNK, but not ERK, were activated by the expression of ASK1DeltaN in PC12 cells. (nih.gov)
  • Furthermore, biopsies of human hepatocellular carcinoma show high expression of p38γ, suggesting that p38γ could be a therapeutic target in the treatment of this disease. (nature.com)
  • Furthermore, by generating novel transgenic lines in which elevated ER stress (caused by the expression of a non-secreted, ER stress-inducing protein) is targeted to relevant chondrocytes in vivo by use of the collagen X or II promoter, we have demonstrated the capability of ER stress to induce chondrodysplasia. (manchester.ac.uk)
Found1
  • We found that IU1 activates AMPK in Huh7 cells, but has no apparent effect in HEK293 cells. (helsinki.fi)
Diseases1
  • Several promising compounds that inhibit p38 alpha are being investigated as potential therapies for arthritic and inflammatory diseases. (rndsystems.com)
Chemicals1
  • In affected indivi- chemicals possessing the ability to react with duals, it has a serious impact on their quality of proteins, and hence these methods do not esti- life. (cdc.gov)
PEPTIDE1
  • Thus, the principle of protein or peptide haptenation could be used in in vitro assays to predict the sensitization potential of a new chemical entity. (cdc.gov)
Role1
  • The role of post-exercise protein ingestion in enhancing the effects of running-based endurance exercise training relative to energy-matched carbohydrate intervention remains to be established. (biomedcentral.com)
Activity1
Specific1
  • Ubiquitin-specific proteases (USP) are involved in the deubiquitination of protein. (helsinki.fi)
Results1
  • These results are surprising in that they contrast with several previous reports describing a requirement for p38 during myogenesis. (biologists.com)
Alpha2
  • This DuoSet IC ELISA contains the basic components required for the development of sandwich ELISAs to measure phosphorylated human, mouse, and rat p38 alpha (T180 / Y182) in cell lysates. (rndsystems.com)
  • The most frequently analyzed family member, p38 alpha, also known as SAPK2a and MAPK14, was initially purified as a kinase critical to the signaling cascade linking IL-1 to MAPKAPK-2 and the small heat shock protein HSP27. (rndsystems.com)
Level1
  • The protein level of phospho-p38 was measured using western blot analysis. (molvis.org)
Human1
  • The protein interaction landscape of the human CMGC kinase group. (nature.com)
Functional1
  • Lundberg, A. S. & Weinberg, R. A. Functional inactivation of the retinoblastoma protein requires sequential modification by at least two distinct cyclin-cdk complexes. (nature.com)
Development1
  • Fig. 3: p38γ drives the development of HCC. (nature.com)
Provide1
  • Taken together, post-endurance exercise protein intake may provide means to facilitate aerobic training adaptations. (biomedcentral.com)
Response1
  • There is increasing evidence that nutrient intake can affect the adaptive response to a single exercise bout, and that protein feeding is important to facilitate this process. (biomedcentral.com)
Complex1
  • The cell cycle is a tightly regulated process that is controlled by the conserved cyclin-dependent kinase (CDK)-cyclin protein complex 1 . (nature.com)