2018
Striatal-Enriched Protein-Tyrosine Phosphatase (STEP)
Kurup P, Xu J, Chatterjee M, Goebel-Goody S, Paul S, Lombroso P. Striatal-Enriched Protein-Tyrosine Phosphatase (STEP). 2018, 5188-5203. DOI: 10.1007/978-3-319-67199-4_630.Peer-Reviewed Original Research
2016
Striatal-Enriched Protein-Tyrosine Phosphatase (STEP)
Kurup P, Xu J, Chatterjee M, Goebel-Goody S, Paul S, Lombroso P. Striatal-Enriched Protein-Tyrosine Phosphatase (STEP). 2016, 1-16. DOI: 10.1007/978-1-4614-6438-9_630-1.Peer-Reviewed Original Research
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
The tyrosine phosphatase STEP: implications in schizophrenia and the molecular mechanism underlying antipsychotic medications
Carty NC, Xu J, Kurup P, Brouillette J, Goebel-Goody SM, Austin DR, Yuan P, Chen G, Correa PR, Haroutunian V, Pittenger C, Lombroso PJ. The tyrosine phosphatase STEP: implications in schizophrenia and the molecular mechanism underlying antipsychotic medications. Translational Psychiatry 2012, 2: e137-e137. PMID: 22781170, PMCID: PMC3410627, DOI: 10.1038/tp.2012.63.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate receptorsSTEP61 levelsSurface expressionPostmortem anterior cingulate cortexGluN2B-containing N-methyl-D-aspartate receptorsGluN1/GluN2B receptorsMK-801 treatmentPathophysiology of schizophreniaAnterior cingulate cortexSTEP knockout miceDorsolateral prefrontal cortexChronic administrationChronic treatmentNeuroleptic treatmentAntipsychotic medicationGlutamatergic functionMK-801Glutamate hypothesisMedications resultsTyrosine phosphatase STEPGlutamatergic signalingKnockout miceGluN2B receptorsCingulate cortexSynaptic plasticityCalpain 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 localizationInhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation
Tautz L, Sergienko E, Xu J, Liu W, Dahl R, Critton D, Su Y, Brown B, Chan X, Yang L, Bobkova E, Vasile S, Yuan H, Rascon J, Colayco S, Sidique S, Cosford N, Chung T, Mustelin T, Page R, Lombroso P. Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation. The FASEB Journal 2012, 26: 766.12-766.12. DOI: 10.1096/fasebj.26.1_supplement.766.12.Peer-Reviewed Original ResearchHematopoietic protein tyrosine phosphataseP38 activationProtein tyrosine phosphataseUnique amino acid residuesAmino acid residuesNew drug targetsCell cycle arrestMAP kinases ERK1/2Activation of ERK1/2Tyrosine phosphataseHePTPMutagenesis experimentsMAP kinaseKinases ERK1/2Acid residuesCatalytic pocketDrug targetsTransient activationCycle arrestT-cell acute lymphoblastic leukemiaERK1/2Prolonged activationHuman T cellsPharmacological inhibitionCancer cellsStriatal-Enriched Protein Tyrosine Phosphatase (STEP)
Kurup P, Xu J, Goebel-Goody S, Paul S, Lombroso P. Striatal-Enriched Protein Tyrosine Phosphatase (STEP). 2012, 1793-1804. DOI: 10.1007/978-1-4419-0461-4_630.Peer-Reviewed Original Research
2011
Striatal-Enriched Protein Tyrosine Phosphatase Expression and Activity in Huntington's Disease: A STEP in the Resistance to Excitotoxicity
Saavedra A, Giralt A, Rué L, Xifró X, Xu J, Ortega Z, Lucas JJ, Lombroso PJ, Alberch J, Pérez-Navarro E. Striatal-Enriched Protein Tyrosine Phosphatase Expression and Activity in Huntington's Disease: A STEP in the Resistance to Excitotoxicity. Journal Of Neuroscience 2011, 31: 8150-8162. PMID: 21632937, PMCID: PMC3472648, DOI: 10.1523/jneurosci.3446-10.2011.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainCalcineurinCell DeathDisease Models, AnimalGene Expression RegulationGene Products, tatHuntingtin ProteinHuntington DiseaseMiceMice, Neurologic MutantsMice, TransgenicMicroinjectionsNerve Tissue ProteinsNuclear ProteinsPhosphorylationProtein Tyrosine Phosphatases, Non-ReceptorQuinolinic AcidSignal TransductionConceptsStriatal-enriched protein tyrosine phosphataseCell deathSTEP expressionPhosphorylation levelsProtein Tyrosine Phosphatase ExpressionProtein tyrosine phosphataseSTEP phosphorylationTyrosine phosphataseProtein kinasePhosphorylated ERK2Phosphatase expressionHuntington's diseaseSTEP proteinMutant huntingtinCalcineurin activityPhosphorylationExon 1STEP protein levelsDisease mouse modelProtein levelsMouse modelMouse striatumTAT-STEPHuntington's disease mouse modelExpression
2010
Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer’s disease mouse model
Zhang Y, Kurup P, Xu J, Carty N, Fernandez SM, Nygaard HB, Pittenger C, Greengard P, Strittmatter SM, Nairn AC, Lombroso PJ. Genetic reduction of striatal-enriched tyrosine phosphatase (STEP) reverses cognitive and cellular deficits in an Alzheimer’s disease mouse model. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 19014-19019. PMID: 20956308, PMCID: PMC2973892, DOI: 10.1073/pnas.1013543107.Peer-Reviewed Original ResearchConceptsStriatal-enriched tyrosine phosphataseTyrosine phosphataseDisease mouse modelStriatal-enriched phosphataseAlzheimer's diseaseCellular deficitsGenetic manipulationNMDA receptorsMouse modelTriple transgenic AD mouse modelIncurable neurodegenerative disorderTransgenic AD mouse modelAlzheimer's disease mouse modelPathophysiology of ADSTEP inhibitorGenetic reductionAD mouse modelHuman AD patientsSoluble Aβ oligomersSynaptic functionPhosphataseNeurodegenerative disordersAD patientsDevastating disorderAnimal modelsAβ-Mediated NMDA Receptor Endocytosis in Alzheimer's Disease Involves Ubiquitination of the Tyrosine Phosphatase STEP61
Kurup P, Zhang Y, Xu J, Venkitaramani DV, Haroutunian V, Greengard P, Nairn AC, Lombroso PJ. Aβ-Mediated NMDA Receptor Endocytosis in Alzheimer's Disease Involves Ubiquitination of the Tyrosine Phosphatase STEP61. Journal Of Neuroscience 2010, 30: 5948-5957. PMID: 20427654, PMCID: PMC2868326, DOI: 10.1523/jneurosci.0157-10.2010.Peer-Reviewed Original ResearchMeSH KeywordsAgedAged, 80 and overAlzheimer DiseaseAmyloid beta-PeptidesAnimalsCell LineCells, CulturedCerebral CortexEndocytosisHumansIn Vitro TechniquesMiceMice, KnockoutMice, TransgenicMiddle AgedNeuronsProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateUbiquitinated ProteinsUbiquitinationConceptsAlzheimer's diseaseAbeta treatmentNR2B subunitProtein tyrosine Phosphatase 61Cognitive deficitsNMDA receptor internalizationHuman AD brainsMouse cortical culturesNR1/NR2B receptorsNMDA receptor endocytosisIonotropic glutamate receptorsTyrosine phosphatase STEP61AD brainCortical slicesCortical culturesGlutamate receptorsNR2B receptorsPostsynaptic terminalsPrefrontal cortexNeuronal membranesElevated levelsCortexReceptor internalizationUbiquitin-proteasome systemStep activity
2009
Extrasynaptic NMDA Receptors Couple Preferentially to Excitotoxicity via Calpain-Mediated Cleavage of STEP
Xu J, Kurup P, Zhang Y, Goebel-Goody SM, Wu PH, Hawasli AH, Baum ML, Bibb JA, Lombroso PJ. Extrasynaptic NMDA Receptors Couple Preferentially to Excitotoxicity via Calpain-Mediated Cleavage of STEP. Journal Of Neuroscience 2009, 29: 9330-9343. PMID: 19625523, PMCID: PMC2737362, DOI: 10.1523/jneurosci.2212-09.2009.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAnimalsBrainCalpainCell DeathCells, CulturedCyclin-Dependent Kinase 5EndocytosisGlutamic AcidIn Vitro TechniquesMiceMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Neuronsp38 Mitogen-Activated Protein KinasesProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleyReceptors, N-Methyl-D-AspartateSynapsesConceptsStriatal-enriched protein tyrosine phosphataseCalpain cleavage sitesP38 activationCell deathCleavage siteExtracellular signal-regulated kinase 1/2Protein tyrosine phosphataseSignal-regulated kinase 1/2Promotes cell survivalActivation of p38Tyrosine phosphataseSubstrate bindingKinase 1/2ERK1/2 activationCalpain cleavageCell survivalNovel mechanismCalpain-mediated proteolysisReceptors coupleP38NMDAR stimulationPostsynaptic terminalsValid targetCleavage productsSTEP substrates
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