Search results for "MAP kinase"

showing 8 items of 178 documents

Cigarette smoke extract activates human bronchial epithelial cells affecting non-neuronal cholinergic system signalling in vitro.

2010

Abstract Aims Acetylcholine (ACh) is synthesized by Choline Acetyl-Transferase (ChAT) that exerts its physiological effects in airway epithelial cells via muscarinic receptor (MR) activation. We evaluate the effect of ACh stimulation on human bronchial epithelial cells (16-HBE) and test whether cigarette smoke extract (CSE) can modify the basal cellular response to ACh affecting the non-neuronal cholinergic system signalling. Main methods ACh stimulated 16-HBE were tested for ACh-binding, Leukotriene B 4 (LTB 4 ) release and ERK1/2 and NFkB pathway activation. Additionally, we investigated all the aforementioned parameters as well as ChAT and MR proteins and mRNA expression and endogenous A…

medicine.medical_specialtyLeukotriene B4Blotting WesternEndogenyStimulationBronchiPharmacologyBiologyComplex MixturesIn Vitro TechniquesLeukotriene B4General Biochemistry Genetics and Molecular BiologyCell LineCholine O-Acetyltransferasechemistry.chemical_compoundInternal medicineSmokeparasitic diseasesMuscarinic acetylcholine receptorTobaccomedicineHumansGeneral Pharmacology Toxicology and PharmaceuticsReceptorExtracellular Signal-Regulated MAP KinasesAnalysis of VarianceReverse Transcriptase Polymerase Chain ReactionNF-kappa BCholine Acetyl-TransferaseAcetylcholine muscarinic receptorhuman bronchial epithelial cellsGeneral MedicineFlow CytometryCholine acetyltransferaseReceptors MuscarinicAcetylcholineEndocrinologychemistryGene Expression RegulationTelenzepineAcetylcholinemedicine.drugSignal Transduction
researchProduct

Increased Connexin 43 Expression as a Potential Mediator of the Neuroprotective Activity of the Corticotropin-Releasing Hormone

2009

CRH is a major central stress mediator, but also a potent neuroprotective effector. The mechanisms by which CRH mediates its neuroprotective actions are largely unknown. Here, we describe that the gap junction molecule connexin43 (Cx43) mediates neuroprotective effects of CRH toward experimentally induced oxidative stress. An enhanced gap junction communication has been reported to contribute to neuroprotection after neurotoxic insults. We show that CRH treatment up-regulates Cx43 expression and gap junctional communication in a CRH receptor-dependent manner in IMR32 neuroblastoma cells, primary astrocytes, and organotypic hippocampal slice cultures. MAPKs and protein kinase A-cAMP response…

medicine.medical_specialtyendocrine systemCorticotropin-Releasing HormoneMAP Kinase Signaling SystemCarbenoxoloneConnexinBiologyNeuroprotectionModels BiologicalArticleRats Sprague-DawleyCorticotropin-releasing hormoneMiceEndocrinologyMediatorInternal medicineCell Line Tumormedicinepolycyclic compoundsAnimalsHumansProtein kinase AMolecular BiologyGap junctionBrainGap JunctionsGeneral MedicineCell biologyRatsEndocrinologyNeuroprotective Agentsnervous systemGene Expression RegulationConnexin 43cardiovascular systemSignal transductionhormones hormone substitutes and hormone antagonistsmedicine.drugSignal Transduction
researchProduct

Activation of the p38MAPK cascade is associated with upregulation of TNF alpha receptors in the spinal motor neurons of mouse models of familial ALS.

2005

Phosphorylated p38 mitogen-activated protein kinase (p38MAPK), but not activated c-jun-N-terminal kinase (JNK), increases in the motor neurons of transgenic mice overexpressing ALS-linked SOD1 mutants at different stages of the disease. This effect is associated with a selective increase of phosphorylated MKK3-6, MKK4 and ASK1 and a concomitant upregulation of the TNFalpha receptors (TNFR1 and TNFR2), but not IL1beta and Fas receptors. Activation of both p38 MAPK and JNK occurs in the activated microglial cells of SOD1 mutant mice at the advanced stage of the disease; however, this effect is not accompanied by the concomitant activation of the upstream kinases ASK1 and MKK3,4,6, while both …

p38 mitogen-activated protein kinasesMAP Kinase Kinase 3Mice TransgenicMAP Kinase Kinase 6BiologyMAP Kinase Kinase Kinase 5p38 Mitogen-Activated Protein KinasesReceptors Tumor Necrosis FactorCellular and Molecular NeuroscienceMiceSuperoxide Dismutase-1Downregulation and upregulationAnimalsHumansASK1RNA Messengerfas ReceptorPhosphorylationReceptorProtein kinase AMolecular BiologyP38MAPK cascadeMotor NeuronsKinaseSuperoxide DismutaseTumor Necrosis Factor-alphaAmyotrophic Lateral SclerosisJNK Mitogen-Activated Protein KinasesReceptors Interleukin-1Cell BiologyCell biologyEnzyme ActivationMice Inbred C57BLDisease Models AnimalTumor Necrosis Factor Decoy ReceptorsSpinal CordReceptors Tumor Necrosis Factor Type IDisease ProgressionTumor necrosis factor alphaSignal TransductionMolecular and cellular neurosciences
researchProduct

Endoderm development requires centrioles to restrain p53-mediated apoptosis in the absence of ERK activity

2021

Centrioles comprise the heart of centrosomes, microtubule-organizing centers. To study the function of centrioles in lung and gut development, we genetically disrupted centrioles throughout the mouse endoderm. Surprisingly, removing centrioles from the endoderm did not disrupt intestinal growth or development but blocked lung branching. In the lung, acentriolar SOX2-expressing airway epithelial cells apoptosed. Loss of centrioles activated p53, and removing p53 restored survival of SOX2-expressing cells, lung branching, and mouse viability. To investigate how endodermal p53 activation specifically killed acentriolar SOX2-expressing cells, we assessed ERK, a prosurvival cue. ERK was active t…

p53Cell SurvivalApoptosisInbred C57BLMedical and Health SciencesArticleGeneral Biochemistry Genetics and Molecular BiologyMiceMorphogenesis2.1 Biological and endogenous factorsAnimalscentrioleintestine developmentAetiologyExtracellular Signal-Regulated MAP KinasesendodermLungMolecular BiologyCentriolesSOXB1 Transcription FactorsStem CellsEndodermapoptosisEpithelial CellsCell BiologyBiological SciencesIntestinesMice Inbred C57BLlung branchingERKembryonic structuresTumor Suppressor Protein p53Microtubule-Associated ProteinsDevelopmental BiologyDevelopmental Cell
researchProduct

Activation of NF-kappaB and IL-8 by yersinia enterocolitica invasin protein is conferred by engagement of rac1 and MAP kinase cascades.

2003

International audience; Yersinia enterocolitica triggers activation of the nuclear factor (NF)-kappaB and production of the proinflammatory chemokine interleukin (IL)-8 in intestinal epithelial cells. This activation is due to adhesion of the bacteria via their outer membrane protein invasin to the host cells. Using Clostridium difficile toxins that specifically inactivate small GTPases, and transfection of inhibitory proteins of the Rho-GTPases, we demonstrate that Rac1, but not Cdc42 or Rho, is required for activation of NF-kappaB by invasin. Invasin activated the mitogen activated protein kinases (MAPK) p38 and c-Jun N-terminal protein kinase (JNK) but not extracellular signal regulated …

rac1 GTP-Binding ProteinMAP Kinase Kinase 4MAP Kinase Signaling SystemRNA Stability[SDV]Life Sciences [q-bio]ImmunologyMitogen-activated protein kinase kinasep38 Mitogen-Activated Protein KinasesMicrobiologyBacterial AdhesionMAP2K703 medical and health sciencesBacterial ProteinsVirologyHumansASK1RNA Messengerc-RafAdhesins Bacterialcdc42 GTP-Binding ProteinrhoB GTP-Binding ProteinYersinia enterocolitica030304 developmental biologyMitogen-Activated Protein Kinase Kinases0303 health sciencesbiologyMAP kinase kinase kinase030306 microbiologyInterleukin-8Cyclin-dependent kinase 2JNK Mitogen-Activated Protein KinasesNF-kappa BProtein kinase RMolecular biologyCell biologybiology.proteinCyclin-dependent kinase 9Mitogen-Activated Protein KinasesrhoA GTP-Binding ProteinHeLa CellsSignal Transduction
researchProduct

Late Activation of Stress-activated Protein Kinases/c-Jun N-terminal Kinases Triggered by Cisplatin-induced DNA Damage in Repair-defective Cells

2011

Although stress-activated protein kinases/c-Jun N-terminal kinases (SAPK/JNK) are rapidly activated by genotoxins, the role of DNA damage in this response is not well defined. Here we show that the SEK1/MKK4-mediated dual phosphorylation of SAPK/JNK (Thr-183/Tyr-185) correlates with the level of cisplatin-DNA adducts at late times (16–24 h) after drug treatment in both human and mouse cells. Transfection of platinated plasmid DNA also caused SAPK/JNK activation. A defect in transcription-coupled nucleotide excision repair resting on a mutation in Cockayne syndrome group B protein promoted the late SAPK/JNK activation following cisplatin exposure. Signaling to SAPK/JNK was accompanied by act…

rho GTP-Binding ProteinsDNA RepairMAP Kinase Kinase 4DNA repairDNA damageDNA damage response; DNA repair; cisplatin-DNA adducts; SAPK/JNKp38 mitogen-activated protein kinasesAntineoplastic AgentsCell Cycle ProteinsAtaxia Telangiectasia Mutated ProteinsProtein Serine-Threonine KinasesDNA and ChromosomesBiologyBiochemistryAtaxia Telangiectasia Mutated ProteinsDNA AdductsMiceRadiation IonizingAnimalsHumansDNA Breaks Double-StrandedMolecular BiologyReplication protein ACells CulturedMice KnockoutKinaseTumor Suppressor ProteinsJNK Mitogen-Activated Protein KinasesCell BiologyMolecular biologyDNA-Binding ProteinsEnzyme Activationc-Jun N-terminal kinasesbiology.proteinCisplatinSignal TransductionNucleotide excision repairJournal of Biological Chemistry
researchProduct

MTOR inhibitor-based combination therapies for pancreatic cancer

2018

Background: Although the mechanistic target of rapamycin (MTOR) kinase, included in the mTORC1 and mTORC2 signalling hubs, has been demonstrated to be active in a significant fraction of patients with pancreatic ductal adenocarcinoma (PDAC), the value of the kinase as a therapeutic target needs further clarification. Methods: We used Mtor floxed mice to analyse the function of the kinase in context of the pancreas at the genetic level. Using a dual-recombinase system, which is based on the flippase-FRT (Flp-FRT) and Cre-loxP recombination technologies, we generated a novel cellular model, allowing the genetic analysis of MTOR functions in tumour maintenance. Cross-species validation and pha…

therapeutic resistance0301 basic medicineCancer ResearchCell SurvivalMAP Kinase Signaling Systempancreatic cancerAntineoplastic AgentsContext (language use)Mechanistic Target of Rapamycin Complex 2mTORC1Mechanistic Target of Rapamycin Complex 1BiologymTORC2BortezomibMice03 medical and health sciencesCell Line TumorPancreatic cancermedicineAnimalsHumansExtracellular Signal-Regulated MAP KinasesMechanistic target of rapamycinPI3K/AKT/mTOR pathwayBenzoxazolesKinaseMTORTOR Serine-Threonine Kinasesmedicine.diseaseddc:3. Good healthPancreatic NeoplasmsPyrimidines030104 developmental biologyOncologybiology.proteinCancer researchCamptothecinTOR Serine-Threonine KinasesPhosphatidylinositol 3-KinaseTranslational TherapeuticsProto-Oncogene Proteins c-aktBiologieCarcinoma Pancreatic Ductal
researchProduct

The mitogen-activated protein kinase p38 pathway is conserved in metazoans: Cloning and activation of p38 of the SAPK2 subfamily from the sponge Sube…

2000

Our recent data suggest that during auto- and allograft recognition in sponges (Porifera), cytokines are differentially expressed. Since the mitogen-activated protein kinase (MAPK) signal transduction modulates the synthesis and release of cytokines, we intended to identify one key molecule of this pathway. Therefore, a cDNA from the marine sponge Suberites domuncula encoding the MAPK was isolated and analyzed. Its encoded protein is 366 amino acids long (calculated Mr 42 209), has a TGY dual phosphorylation motif in protein kinase subdomain VIII and displays highest overall similarity to the mammalian p38 stress activated protein kinase (SAPK2), one subfamily of MAPKs. The sponge protein w…

xHot TemperatureUltraviolet RaysMolecular Sequence DataMarine BiologyBiologyMitogen-activated protein kinase kinasep38 Mitogen-Activated Protein KinasesMAP2K7Osmotic PressureAnimalsASK1Amino Acid Sequencec-RafGenes Immediate-EarlyConserved SequencePhylogenyGene LibraryModels GeneticSequence Homology Amino AcidMAP kinase kinase kinaseCyclin-dependent kinase 2Hydrogen PeroxideCell BiologyGeneral Medicinebiology.organism_classificationPoriferaEnzyme ActivationSuberites domunculaBiochemistrybiology.proteinCyclin-dependent kinase 9Mitogen-Activated Protein KinasesSequence AnalysisSignal TransductionBiology of the Cell
researchProduct