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MKP5 allostery in MAPK regulation and signaling in the heart
Organization YALE UNIVERSITYLocation NEW HAVEN, UNITED STATESPosted 18 Jan 2022Deadline 31 Dec 2025 ⚠️
NIHUS FederalResearch GrantFY2025AdoptedAllosteric SiteBindingBinding SitesBiologyBody TissuesBone-Derived Transforming Growth FactorC-jun Amino-Terminal KinaseC-jun Kinase-1C-jun N-Terminal Kinase 1CRISPR approachCRISPR based approachCRISPR methodCRISPR methodologyCRISPR techniqueCRISPR technologyCRISPR toolsCRISPR-CAS-9CRISPR-based methodCRISPR-based techniqueCRISPR-based technologyCRISPR-based toolCRISPR/CAS approachCRISPR/Cas methodCRISPR/Cas technologyCRISPR/Cas9CRISPR/Cas9 technologyCSAID-Binding Protein 1CSAID-Binding Protein 2CSBP2Cas nuclease technologyCatalysisCatalytic CoreCatalytic DomainCatalytic RegionCatalytic SiteCatalytic SubunitCell BodyCell Communication and SignalingCell SignalingCellsCellular biologyChemicalsClinicalClustered Regularly Interspaced Short Palindromic Repeats approachClustered Regularly Interspaced Short Palindromic Repeats methodClustered Regularly Interspaced Short Palindromic Repeats methodologyClustered Regularly Interspaced Short Palindromic Repeats techniqueClustered Regularly Interspaced Short Palindromic Repeats technologyCombining SiteComplexCoupledCytokine-Suppressive Antiinflammatory Drug-Binding Protein 1Cytokine-Suppressive Antiinflammatory Drug-Binding protein 2DataDephosphorylationDevelopmentDiseaseDisorderDrug TherapyEffectivenessExperimental ModelsFibrosis in the heartFibrosis in the myocardiumFibrosis within the heartFibrosis within the myocardiumFibrotic myocardiumFingerprintGenerationsGeneticGoalsHeartHeart failureIntracellular Communication and SignalingJN KinaseJNKJNK Mitogen-Activated Protein KinasesJNK1JNK1 KinaseJNK1 proteinJNK1A2JNK21B1/2KI miceKineticsKnock-inKnock-in MouseMAP Kinase 8MAP Kinase 8 GeneMAP kinaseMAPK14MAPK14 Mitogen-Activated Protein KinaseMAPK14 geneMAPK8MAPK8 Mitogen-Activated Protein KinaseMAPK8 geneMediatingMiceMice MammalsMilk Growth FactorMitogen-Activated Protein Kinase 14Mitogen-Activated Protein Kinase 8Mitogen-Activated Protein KinasesModelingMolecularMolecular InteractionMorbidityMorbidity - disease rateMurineMusMxi2OutcomePRKM8Pathway interactionsPharmacological TreatmentPharmacotherapyPhosphatasesPhosphohydrolasesPhosphomonoesterasesPhosphoric Monoester HydrolasesPhysiologicPhysiologicalPlatelet Transforming Growth FactorPlayProtein DephosphorylationProtein Kinase InteractionProteomicsReactive SiteRegulationResolutionRoleSAP Kinase-1SAPK/JNKSAPK1 Mitogen-Activated Protein KinaseSAPK1/JNKSAPK2ASignal TransductionSignal Transduction SystemsSignalingSiteSpecificityStress-Activated Protein Kinase 2AStress-Activated Protein Kinase JNK1Stress-Activated Protein Kinase gammaStructureTGF BTGF-betaTGF-βTGFbetaTGFβTherapeuticTissuesTransforming Growth Factor betaTransforming Growth Factor-Beta Family GeneUnited StatesWorkbiological signal transductionbiophysical approachesbiophysical methodologybiophysical methodsbiophysical techniquesc-jun N-Terminal Kinasecardiac failurecardiac fibrosiscell biologycoronary fibrosisdevelopmentaldrug interventiondrug treatmentdruggable targetfibrogenesisfibrotic heartgenetic approachgenetic strategyheart fibrosisin vivoinhibitorinsightjun-NH2-Terminal Kinaseknockinknockin micemortalitymouse geneticsmutantmyocardial fibrosisnoveloperationoperationsp38p38 MAP Kinasep38 MAPK Genep38 Mitogen Activated Protein Kinasep38 Protein Kinasep38 SAPKp38-Alphap38Alphapathwaypharmaceutical interventionpharmacological interventionpharmacological therapypharmacology interventionpharmacology treatmentpharmacotherapeuticsphosphatase inhibitorphospho-proteomicsphosphoproteomicspressureresolutionssmall moleculesocial rolestress-activated protein kinase 1structural biologystructural determinantsstructural factorstherapeutic targettranscriptomics
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Description preview
ABSTRACT
The catalytic activity and specificity of the mitogen-activated protein kinase (MAPK) phosphatases (MKPs) is
governed through their ability to interact with the MAPKs. The MKPs set the fidelity and kinetics of MAPK
signaling by regulating, in a spatially distinct manner, both the magnitude and duration of MAPK activity.
However, these…
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