Search results for "MAP kinase"

showing 10 items of 178 documents

Activation of mitogen-activated protein kinase by the bradykinin B2receptor is independent of receptor phosphorylation and phosphorylation-triggered …

1999

Recent evidence suggests that serine/threonine phosphorylation and internalization of beta2-adrenergic receptors play critical roles in signalling to the mitogen-activated protein kinase cascade. To investigate whether this represents a general mechanism employed by G protein-coupled receptors, we studied the requirement of these processes in the activation of mitogen-activated protein kinase by G alpha(q)-coupled bradykinin B2 receptors. Mutant B2 receptors impaired in receptor phosphorylation and internalization are fully capable to activate mitogen-activated protein kinase. Bradykinin-induced long-term effects on mitogenic signalling monitored by measuring the transcriptional activity of…

Receptor Bradykinin B2Bradykinin B2 receptorBiophysicsMitogen-activated protein kinase kinaseBradykininBiochemistryCell LineMAP2K7Structural BiologyMitogenic signallingGeneticsHumansPhosphorylationBradykinin receptorProtein kinase AMolecular BiologyProtein kinase CG protein-coupled receptorG protein-coupled receptor kinaseMAP kinase kinase kinaseChemistryReceptors BradykininCell BiologyMitogen-activated protein kinaseEnzyme ActivationBiochemistryCalcium-Calmodulin-Dependent Protein KinasesInternalizationSignal TransductionFEBS Letters
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Endothelial cells and normal breast epithelial cells enhance invasion of breast carcinoma cells by CXCR-4-dependent up-regulation of urokinase-type p…

2008

Here we show the increase of invasion of three breast cancer cell lines (8701-BC, MDA-MB-231 and SKBR3) upon long-term co-incubation with culture medium of normal microvascular endothelial cells (MVEC) and normal breast epithelial cells (HB2). The enhancement of invasion relied on the interaction of microvascular endothelial cell and normal breast epithelial cell CXCL12 (SDF1) chemokine, whose expression by breast cancer cells was very low, with the cognate CXCR4 receptor of malignant cells, which resulted in over-expression of the urokinase-type plasminogen activator receptor (uPAR) on their surfaces. uPAR over-expression, showed by RT-PCR and Western blotting, was paralleled by increased …

Receptors CXCR4MAP Kinase Kinase 4AngiogenesisCellBreast NeoplasmsReceptors Cell SurfaceCell CommunicationBiologyCell LineReceptors Urokinase Plasminogen ActivatorPathology and Forensic MedicineMetastasisangiogenesisbreast cancerTumor Cells CulturedmedicineHumansNeoplasm InvasivenessBreastSettore BIO/06 - Anatomia Comparata E CitologiaPhosphorylationskin and connective tissue diseasesCXCR4Settore MED/04 - Patologia GeneraleNeovascularization PathologicReverse Transcriptase Polymerase Chain ReactionFibrinolysisEpithelial CellsCXCL12invasionmedicine.diseasemicroenvironmentChemokine CXCL12Neoplasm ProteinsUp-RegulationEndothelial stem cellUrokinase receptormedicine.anatomical_structureCulture Media ConditionedCancer cellCancer researchFemaleJNKEndothelium VascularBreast diseaseSDF1uPARPlasminogen activatorThe Journal of Pathology
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Decreased SAPK/JNK signalling affects cytokine release and STAT3 activation in psoriatic fibroblasts.

2015

STAT3 Transcription FactorMAP Kinase Signaling Systemmedicine.medical_treatmentDermatologyBiochemistryp38 Mitogen-Activated Protein KinasesPsoriasismedicineSapk jnkHumansPsoriasisPhosphorylationSTAT3Molecular BiologyStat3 activationMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3biologyChemistryInterleukin-6Tumor Necrosis Factor-alphaInterleukin-8JNK Mitogen-Activated Protein KinasesTranscription Factor RelAFibroblastsmedicine.diseaseSignallingCytokineCase-Control StudiesCancer researchbiology.proteinPhosphorylationTumor necrosis factor alphaExperimental dermatology
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Tristetraprolin regulation of interleukin-22 production

2015

AbstractInterleukin (IL)-22 is a STAT3-activating cytokine displaying characteristic AU-rich elements (ARE) in the 3′-untranslated region (3′-UTR) of its mRNA. This architecture suggests gene regulation by modulation of mRNA stability. Since related cytokines undergo post-transcriptional regulation by ARE-binding tristetraprolin (TTP), the role of this destabilizing protein in IL-22 production was investigated. Herein, we demonstrate that TTP-deficient mice display augmented serum IL-22. Likewise, IL-22 mRNA was enhanced in TTP-deficient splenocytes and isolated primary T cells. A pivotal role for TTP is underscored by an extended IL-22 mRNA half-life detectable in TTP-deficient T cells. Lu…

STAT3 Transcription Factormedicine.medical_treatmentT-LymphocytesTristetraprolinPrimary Cell CultureMAP Kinase Kinase 1BiologyJurkat cellsArticleInterleukin 22Jurkat CellsMiceTristetraprolinNitrilesmedicineButadienesAnimalsHumansRNA Messengerddc:610Regulation of gene expressionAU-rich elementAU Rich ElementsInflammationMultidisciplinaryInterleukinsHEK 293 cellsInterleukinCell biologyCytokineHEK293 CellsGene Expression RegulationImmunologyErratumScientific Reports
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Convergence of the target of rapamycin and the Snf1 protein kinase pathways in the regulation of the subcellular localization of Msn2, a transcriptio…

2002

The subcellular localization of Msn2, a transcriptional activator of STRE (stress response element)-regulated genes, is modulated by carbon source availability. In cells growing in glucose, Msn2 is located mainly in the cytosol, whereas in carbon source-starved cells, Msn2 is located largely inside the nucleus. However, in cells lacking Reg1 (the regulatory subunit of the Reg1/Glc7 protein phosphatase complex), the regulation of subcellular distribution is absent, Msn2 being constitutively present in the cytosol. The localization defect in these mutants is specific for carbon starvation stress, and it is because of the presence of an abnormally active Snf1 protein kinase that inhibits the n…

Saccharomyces cerevisiae ProteinsRecombinant Fusion ProteinsSaccharomyces cerevisiaeMitogen-activated protein kinase kinaseBiologyProtein Serine-Threonine KinasesBiochemistryASK1Molecular BiologyDNA PrimersSirolimusMAP kinase kinase kinaseBase SequenceKinaseCell BiologySubcellular localizationCarbonCell biologyCulture MediaDNA-Binding ProteinsCytosolBiochemistryTrans-ActivatorsCyclin-dependent kinase 9Nuclear localization sequenceSubcellular FractionsTranscription FactorsThe Journal of biological chemistry
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The development of benzimidazoles as selective rho kinase inhibitors

2010

Rho Kinase (ROCK) is a serine/threonine kinase whose inhibition could prove beneficial in numerous therapeutic areas. We have developed a promising class of ATP-competitive inhibitors based upon a benzimidazole scaffold, which show excellent potency toward ROCK (IC(50)<10nM). This report details the optimization of selectivity for ROCK over other related kinases such as Protein kinase A (PKA).

Serine/threonine-specific protein kinaserho-Associated KinasesMAP kinase kinase kinaseChemistryKinaseOrganic ChemistryClinical BiochemistryPharmaceutical ScienceGlaucomaChromanMitogen-activated protein kinase kinaseBiochemistryBenzimidazoleBiochemistryDrug DiscoveryROCKMolecular MedicineBenzimidazolesCyclin-dependent kinase 9Protein kinase ARho KinaseProtein Kinase InhibitorsMolecular BiologyRho-associated protein kinaseProtein kinase CBioorganic & Medicinal Chemistry Letters : a tetrahedron publication for the rapid dissemination of preliminary communication and all aspects of bioorganic chemistry, medicinal chemistry and related disciplines
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The mitotic kinase Aurora-A promotes distant metastases by inducing epithelial-to-mesenchymal transition in ERα+ breast cancer cells

2013

In this study, we demonstrate that constitutive activation of Raf-1 oncogenic signaling induces stabilization and accumulation of Aurora-A mitotic kinase that ultimately drives the transition from an epithelial to a highly invasive mesenchymal phenotype in estrogen receptor α-positive (ERα(+)) breast cancer cells. The transition from an epithelial- to a mesenchymal-like phenotype was characterized by reduced expression of ERα, HER-2/Neu overexpression and loss of CD24 surface receptor (CD24(-/low)). Importantly, expression of key epithelial-to-mesenchymal transition (EMT) markers and upregulation of the stemness gene SOX2 was linked to acquisition of stem cell-like properties such as the ab…

Smad5 ProteinCancer ResearchEpithelial-Mesenchymal TransitionMAP Kinase Signaling SystemReceptor ErbB-2Active Transport Cell NucleusEstrogen receptorMice NudeBreast NeoplasmsBiologyArticleMicebreast cancerSOX2Cell MovementCell Line TumorGeneticsAnimalsHumansEpithelial–mesenchymal transitionKinase activityNeoplasm MetastasisPhosphorylationRNA Small InterferingMolecular BiologyAurora Kinase Ametastases mitosisSOXB1 Transcription FactorsEstrogen Receptor alphaCD24 AntigenXenograft Model Antitumor AssaysstemneGene Expression Regulation NeoplasticProto-Oncogene Proteins c-rafSettore BIO/18 - GeneticaTumor progressionembryonic structuresCancer researchMCF-7 CellsNeoplastic Stem CellsProto-Oncogene Proteins c-rafFemaleRNA InterferenceSignal transductionEstrogen receptor alphaNeoplasm Transplantation
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A systems biology perspective on cholangiocellular carcinoma development: focus on MAPK-signaling and the extracellular environment.

2008

Background/Aims Multiple genes have been implicated in cholangiocellular carcinoma (CCC) development. However, the overall neoplastic risk is likely associated with a much lower number of critical physiological pathways. Methods To investigate this hypothesis, we extracted all published genetic associations for the development of CCC from PubMed (genetic association studies, but also studies associating genes and CCC in general, i.e. functional studies in cell lines, genetic studies in humans, knockout mice etc.) and integrated CCC microarray data. Results We demonstrated the MAPK pathway was consistently enriched in CCC. Comparing our data to genetic associations in HCC often successfully …

SorafenibMAPK/ERK pathwayNiacinamideMAP Kinase Signaling SystemPyridinesSystems biologyAntineoplastic AgentsOncogenomicsBiologyCholangiocarcinomaMiceDatabases GeneticmedicineAnimalsHumansGeneOligonucleotide Array Sequence AnalysisHepatologyMicroarray analysis techniquesKinasePhenylurea CompoundsSystems BiologyBenzenesulfonatesComputational BiologySorafenibBiological EvolutionBile Ducts IntrahepaticBile Duct NeoplasmsMultigene FamilyImmunologyKnockout mouseCancer researchExtracellular Spacemedicine.drugJournal of hepatology
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Hematopoietic stem cell quiescence and function are controlled by the CYLD–TRAF2–p38MAPK pathway

2015

Tesio at al. identify a novel pathway controlled by the tumor suppressor and deubiquitinase cylindromatosis (CYLD), which is involved in the regulation of hematopoietic stem cell quiescence and repopulation potential.

TRAF2Tumor suppressor geneMAP Kinase Signaling SystemImmunologyRegulatorBiologyp38 Mitogen-Activated Protein KinasesArticleMicemedicineAnimalsImmunology and AllergyMice KnockoutRegulation of gene expressionNF-kappa BHematopoietic stem cellCell BiologyHematopoietic Stem CellsTNF Receptor-Associated Factor 2PhenotypeDeubiquitinating Enzyme CYLDCell biologyCysteine EndopeptidasesHaematopoiesismedicine.anatomical_structureGene Expression RegulationMutationStem cellJournal of Experimental Medicine
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JNK phosphorylation relieves HDAC3-dependent suppression of the transcriptional activity of c-Jun

2003

The AP-1 transcription factor c-Jun is a prototypical nuclear effector of the JNK signal transduction pathway. The integrity of JNK phosphorylation sites at serines 63/73 and at threonines 91/93 in c-Jun is essential for signal-dependent target gene activation. We show that c-Jun phosphorylation mediates dissociation of an inhibitory complex, which is associated with histone deacetylase 3 (HDAC3). The subsequent events that ultimately cause increased mRNA synthesis are independent of c-Jun phosphorylation and its interaction with JNK. These findings provide an 'activation by de-repression' model as an explanation for the stimulatory function of JNK on c-Jun.

ThreonineTranscriptional ActivationTranscription GeneticMAP Kinase Kinase 4Proto-Oncogene Proteins c-junRecombinant Fusion ProteinsMitogen-activated protein kinase kinaseHistone DeacetylasesGeneral Biochemistry Genetics and Molecular BiologyCell LinePhosphorylation cascadeMiceSuppression GeneticGenes ReporterSerineAnimalsHumansRNA MessengerPhosphorylationMolecular BiologyTranscription factorSequence DeletionMitogen-Activated Protein Kinase KinasesGeneral Immunology and MicrobiologybiologyGeneral Neurosciencec-junJNK Mitogen-Activated Protein KinasesArticles3T3 CellsHDAC3Molecular biologyProtein Structure TertiaryMitogen-activated protein kinaseMutationMutagenesis Site-Directedbiology.proteinPhosphorylationSignal transductionProtein BindingThe EMBO Journal
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