2014
Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease
Xu J, Chatterjee M, Baguley TD, Brouillette J, Kurup P, Ghosh D, Kanyo J, Zhang Y, Seyb K, Ononenyi C, Foscue E, Anderson GM, Gresack J, Cuny GD, Glicksman MA, Greengard P, Lam TT, Tautz L, Nairn AC, Ellman JA, Lombroso PJ. Inhibitor of the Tyrosine Phosphatase STEP Reverses Cognitive Deficits in a Mouse Model of Alzheimer's Disease. PLOS Biology 2014, 12: e1001923. PMID: 25093460, PMCID: PMC4122355, DOI: 10.1371/journal.pbio.1001923.Peer-Reviewed Original ResearchMeSH KeywordsAlzheimer DiseaseAmino Acid SequenceAnimalsBenzothiepinsCatalytic DomainCell DeathCerebral CortexCognition DisordersCysteineDisease Models, AnimalEnzyme InhibitorsHigh-Throughput Screening AssaysHumansMaleMice, Inbred C57BLMice, KnockoutMolecular Sequence DataNeuronsPhosphorylationPhosphotyrosineProtein Tyrosine Phosphatases, Non-ReceptorSubstrate SpecificityConceptsInhibitors of stepsSpecificity of inhibitorsIsoxazolepropionic acid receptor (AMPAR) traffickingCatalytic cysteinePTP inhibitorsTyrosine phosphataseTyrosine phosphorylationSecondary assaysSTEP KO miceReceptor traffickingFirst large-scale effortN-methyl-D-aspartate receptorsPyk2 activitySTEP inhibitorLarge-scale effortsNovel therapeutic targetSynaptic functionAlzheimer's diseaseNeurodegenerative disordersCortical cellsTherapeutic targetERK1/2Specificity experimentsPhosphataseInhibitors
2012
Striatal-enriched Protein-tyrosine Phosphatase (STEP) Regulates Pyk2 Kinase Activity*
Xu J, Kurup P, Bartos JA, Patriarchi T, Hell JW, Lombroso PJ. Striatal-enriched Protein-tyrosine Phosphatase (STEP) Regulates Pyk2 Kinase Activity*. Journal Of Biological Chemistry 2012, 287: 20942-20956. PMID: 22544749, PMCID: PMC3375518, DOI: 10.1074/jbc.m112.368654.Peer-Reviewed Original ResearchConceptsStriatal-enriched protein tyrosine phosphataseProtein tyrosine phosphataseN-Methyl-d-aspartate (NMDA) Receptor TraffickingFocal adhesion kinase familyPyk2 activationProline-rich tyrosine kinase 2Pyk2 kinase activityTyrosine kinase 2Kinase familyKinase membersCytoskeletal reorganizationDiverse functionsKinase activitySTEP KO miceReceptor traffickingKinase 2Tyrosine sitesPyk2 activityEnhanced phosphorylationCell adhesionPyk2PhosphorylationFunctional studiesHematopoietic cellsPostsynaptic densityCalpain and STriatal-Enriched protein tyrosine Phosphatase (STEP) activation contribute to extrasynaptic NMDA receptor localization in a Huntington's disease mouse model
Gladding CM, Sepers MD, Xu J, Zhang LY, Milnerwood AJ, Lombroso PJ, Raymond LA. Calpain and STriatal-Enriched protein tyrosine Phosphatase (STEP) activation contribute to extrasynaptic NMDA receptor localization in a Huntington's disease mouse model. Human Molecular Genetics 2012, 21: 3739-3752. PMID: 22523092, PMCID: PMC3412376, DOI: 10.1093/hmg/dds154.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalpainCoculture TechniquesDisease Models, AnimalEnzyme ActivationEnzyme InhibitorsHuntington DiseaseIon Channel GatingMiceModels, BiologicalNeostriatumNeuronsPhosphorylationPhosphotyrosineProtein TransportProtein Tyrosine Phosphatases, Non-ReceptorReceptors, N-Methyl-D-AspartateSynapsesConceptsYAC128 striatumProtein tyrosine phosphatase activationNMDAR localizationCalpain cleavageProtein tyrosine phosphataseTyrosine phosphatase activationEarly synaptic defectsWhole-cell NMDAR currentsDisease mouse modelGluN2B expressionNMDA receptor traffickingMutant huntingtin proteinCalpain inhibitionTyrosine phosphataseHuntington's diseaseFull-length mhttPlasma membranePhosphatase activationC-terminusReceptor traffickingNMDAR traffickingPolyglutamine repeatsMouse modelHuntingtin proteinNMDA receptor localization