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
2013
Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia
Deb I, Manhas N, Poddar R, Rajagopal S, Allan AM, Lombroso PJ, Rosenberg GA, Candelario-Jalil E, Paul S. Neuroprotective Role of a Brain-Enriched Tyrosine Phosphatase, STEP, in Focal Cerebral Ischemia. Journal Of Neuroscience 2013, 33: 17814-17826. PMID: 24198371, PMCID: PMC3818554, DOI: 10.1523/jneurosci.2346-12.2013.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain IschemiaCells, CulturedCorpus StriatumDown-RegulationMaleMiceNeuronsP38 Mitogen-Activated Protein KinasesProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleyRats, WistarSignal TransductionStrokeConceptsIschemic brain damageStriatal-enriched phosphataseBrain damageNeuroprotective roleBrain injuryP38 MAPK activationSustained p38 MAPK activationIschemic brain injuryFocal cerebral ischemiaOnset of reperfusionHypoxia-reoxygenation injuryP38 MAPKMAPK activationIschemic strokeNeurological deficitsCerebral ischemiaStroke therapyKO miceRat modelP38 MAPK pathwayCultured neuronsNeuronal culturesGenetic deletionSecondary activationInjurySubstrate-Based Fragment Identification for the Development of Selective, Nonpeptidic Inhibitors of Striatal-Enriched Protein Tyrosine Phosphatase
Baguley TD, Xu HC, Chatterjee M, Nairn AC, Lombroso PJ, Ellman JA. Substrate-Based Fragment Identification for the Development of Selective, Nonpeptidic Inhibitors of Striatal-Enriched Protein Tyrosine Phosphatase. Journal Of Medicinal Chemistry 2013, 56: 7636-7650. PMID: 24083656, PMCID: PMC3875168, DOI: 10.1021/jm401037h.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBiphenyl CompoundsBlood-Brain BarrierBoronic AcidsCells, CulturedCerebral CortexHumansNeuronsPermeabilityPhosphorous AcidsProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleySmall Molecule LibrariesStereoisomerismStructure-Activity RelationshipSubstrate SpecificityConceptsSubstrate Activity ScreeningProtein tyrosine phosphatase activityProtein tyrosine phosphataseTyrosine phosphatase activityGlutamate receptor internalizationOptimization of fragmentsTyrosine phosphataseDual specificityReceptor internalizationDevelopment of SelectiveSTEP inhibitorPhosphatase activityAlzheimer's diseaseIonotropic glutamate receptorsSubstrate-based approachNonpeptidic inhibitorsPotential targetAD mouse modelDrug discoveryRat cortical neuronsActivity screeningCortical neuronsGlutamate receptorsMouse modelNeuropsychiatric disordersCocaine-Induced Changes of Synaptic Transmission in the Striatum are Modulated by Adenosine A2A Receptors and Involve the Tyrosine Phosphatase STEP
Chiodi V, Mallozzi C, Ferrante A, Chen JF, Lombroso PJ, Di Stasi AM, Popoli P, Domenici MR. Cocaine-Induced Changes of Synaptic Transmission in the Striatum are Modulated by Adenosine A2A Receptors and Involve the Tyrosine Phosphatase STEP. Neuropsychopharmacology 2013, 39: 569-578. PMID: 23989619, PMCID: PMC3895235, DOI: 10.1038/npp.2013.229.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCerebral CortexCocaineCorpus StriatumDopamine Uptake InhibitorsEnzyme InhibitorsGene Expression RegulationHumansIn Vitro TechniquesInhibitory Postsynaptic PotentialsMaleMiceMice, Inbred C57BLMice, KnockoutNeural PathwaysNeuronsProtein Tyrosine Phosphatases, Non-ReceptorReceptor, Adenosine A2ASynaptic TransmissionSynaptosomesVanadatesConceptsEffects of cocaineSynaptic transmissionAdenosine A2A receptorsStriatal-enriched protein tyrosine phosphatasePharmacological actionsA2A receptorsWhole-cell voltage-clamp recordingsA2AR antagonist ZM241385Excitatory post-synaptic currentsCocaine-induced reductionMedium spiny neuronsCocaine-induced changesVoltage-clamp recordingsPost-synaptic currentsA2AR knockout miceCorticostriatal slicesStriatal slicesPsychomotor effectsSpiny neuronsSynaptic mechanismsAntagonist ZM241385Synaptic depressionClamp recordingsBrain areasStriatum
2012
The tyrosine phosphatase STEP constrains amygdala-dependent memory formation and neuroplasticity
Olausson P, Venkitaramani D, Moran T, Salter M, Taylor J, Lombroso P. The tyrosine phosphatase STEP constrains amygdala-dependent memory formation and neuroplasticity. Neuroscience 2012, 225: 1-8. PMID: 22885232, PMCID: PMC3725644, DOI: 10.1016/j.neuroscience.2012.07.069.Peer-Reviewed Original ResearchMeSH KeywordsAmygdalaAnalysis of VarianceAnimalsBiophysicsConditioning, OperantElectric StimulationExcitatory Postsynaptic PotentialsFearMaleMAP Kinase Signaling SystemMemoryMiceMice, Inbred C57BLMice, TransgenicNeuronal PlasticityPatch-Clamp TechniquesProtein Tyrosine Phosphatases, Non-ReceptorReinforcement ScheduleReinforcement, PsychologyConceptsSynaptic plasticityExperience-dependent synaptic plasticityAspartic acid (NMDA) receptorsMemory formationLong-term potentiationAdult neuroplasticityAmygdala-dependent memory formationPharmacological treatmentKO miceExperience-induced neuroplasticityTyrosine phosphatase STEPNR2B subunitLateral amygdalaBrain regionsTyrosine kinase FynAcid receptorsStriatal-enriched protein tyrosine phosphataseNeuroplasticityMiceERK phosphorylationReceptor internalizationERK signalingKinase 1/2Detectable expressionSTEP KO miceThe 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 ResearchMeSH KeywordsAnalysis of VarianceAnimalsAntipsychotic AgentsDizocilpine MaleateGyrus CinguliHumansMaleMiceMice, Inbred C57BLMice, KnockoutPhencyclidinePhosphorylationPrefrontal CortexProtein Tyrosine Phosphatases, Non-ReceptorReceptors, N-Methyl-D-AspartateSchizophreniaConceptsN-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 localizationGenetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model
Goebel‐Goody S, Wilson‐Wallis E, Royston S, Tagliatela S, Naegele J, Lombroso P. Genetic manipulation of STEP reverses behavioral abnormalities in a fragile X syndrome mouse model. Genes Brain & Behavior 2012, 11: 586-600. PMID: 22405502, PMCID: PMC3922131, DOI: 10.1111/j.1601-183x.2012.00781.x.Peer-Reviewed Original ResearchConceptsFragile X syndromeFragile X syndrome mouse modelProtein tyrosine phosphataseMental retardation proteinMRNAs downstreamControl translationTyrosine phosphataseGenetic manipulationGenetic basisFMR1 geneLoss of stepsX syndromeSyndrome mouse modelFMRPReceptor activationGlutamate receptor activationExcess levelsSynaptic strengthSynaptic strengtheningBasal levelsC-Fos activationActivationTranscriptionFynMouse model
2011
Therapeutic Implications for Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Neuropsychiatric Disorders
Goebel-Goody SM, Baum M, Paspalas CD, Fernandez SM, Carty NC, Kurup P, Lombroso PJ. Therapeutic Implications for Striatal-Enriched Protein Tyrosine Phosphatase (STEP) in Neuropsychiatric Disorders. Pharmacological Reviews 2011, 64: 65-87. PMID: 22090472, PMCID: PMC3250079, DOI: 10.1124/pr.110.003053.Peer-Reviewed Original ResearchMeSH KeywordsBrainDimerizationHumansMental DisordersNervous System DiseasesPhosphorylationProtein ConformationProtein Tyrosine Phosphatases, Non-ReceptorSubstrate SpecificityConceptsStriatal-enriched protein tyrosine phosphataseProtein tyrosine phosphataseTyrosine phosphataseStress-activated protein kinase p38Extracellular regulated kinases 1Brain-specific phosphataseSrc family tyrosine kinase FynProtein kinase p38Tyrosine kinase FynN-methyl-D-aspartate receptorsFragile X syndromeDephosphorylation of ERK1/2Stroke/ischemiaSurface NMDARsKinase FynAlcohol-induced memory lossDiverse neuropsychiatric disordersLocal translationKinase 1Kinase p38STEP expressionX syndromeNeuronal functionDephosphorylationFunction contributesStriatal-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 modelExpressionStriatal‐enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced hippocampal memory
Venkitaramani DV, Moura PJ, Picciotto MR, Lombroso PJ. Striatal‐enriched protein tyrosine phosphatase (STEP) knockout mice have enhanced hippocampal memory. European Journal Of Neuroscience 2011, 33: 2288-2298. PMID: 21501258, PMCID: PMC3118976, DOI: 10.1111/j.1460-9568.2011.07687.x.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBehavior, AnimalFocal Adhesion Kinase 2HippocampusMemoryMiceMice, Inbred C57BLMice, KnockoutMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3PhosphorylationProtein Tyrosine Phosphatases, Non-ReceptorReceptors, AMPAReceptors, N-Methyl-D-AspartateSynaptic TransmissionConceptsStriatal-enriched protein tyrosine phosphataseSTEP KO miceProtein tyrosine phosphataseBrain-specific phosphataseProline-rich tyrosine kinaseEffect of deletionN-methyl-D-aspartate receptorsERK1/2 substratesNR1/NR2B N‐Methyl‐d‐Aspartate ReceptorsPotential molecular mechanismsTyrosine phosphataseSignaling proteinsTyrosine phosphorylationDownstream effectorsKinase 1/2Molecular mechanismsTyrosine kinaseFunctional importanceKnockout micePhosphorylationSTEP knockout miceSynaptic strengtheningIsoxazole propionic acid (AMPA) receptorsSynaptosomal expressionRegulation
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 ResearchMeSH KeywordsAlzheimer DiseaseAmyloid beta-Protein PrecursorAnimalsCerebral CortexDisease Models, AnimalEnzyme InhibitorsHumansMiceMice, TransgenicProtein Tyrosine Phosphatases, Non-ReceptorReceptors, N-Methyl-D-AspartateConceptsStriatal-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
2008
The Tyrosine Phosphatase STEP Mediates AMPA Receptor Endocytosis after Metabotropic Glutamate Receptor Stimulation
Zhang Y, Venkitaramani DV, Gladding CM, Zhang Y, Kurup P, Molnar E, Collingridge GL, Lombroso PJ. The Tyrosine Phosphatase STEP Mediates AMPA Receptor Endocytosis after Metabotropic Glutamate Receptor Stimulation. Journal Of Neuroscience 2008, 28: 10561-10566. PMID: 18923032, PMCID: PMC2586105, DOI: 10.1523/jneurosci.2666-08.2008.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCells, CulturedEndocytosisHippocampusMaleMethoxyhydroxyphenylglycolMiceMice, KnockoutNeuronsProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleyReceptors, AMPAReceptors, Metabotropic GlutamateConceptsStriatal-enriched protein tyrosine phosphataseProtein tyrosine phosphataseTyrosine phosphataseAMPAR internalizationMitogen-activated protein kinasePhosphoinositide-3-kinase (PI3K) pathwayAMPA receptor endocytosisTyrosine dephosphorylationAMPA receptor traffickingReceptor endocytosisProtein kinaseKinase pathwayStimulation of mGluR5Receptor traffickingNMDAR endocytosisAMPAR traffickingEndocytosisMetabotropic glutamate receptor stimulationTraffickingSurface expressionInternalizationGlutamate receptor stimulationSynaptic plasticityCentral eventPhosphatase
2007
Status Epilepticus-Induced Somatostatinergic Hilar Interneuron Degeneration Is Regulated by Striatal Enriched Protein Tyrosine Phosphatase
Choi YS, Lin SL, Lee B, Kurup P, Cho HY, Naegele JR, Lombroso PJ, Obrietan K. Status Epilepticus-Induced Somatostatinergic Hilar Interneuron Degeneration Is Regulated by Striatal Enriched Protein Tyrosine Phosphatase. Journal Of Neuroscience 2007, 27: 2999-3009. PMID: 17360923, PMCID: PMC2701360, DOI: 10.1523/jneurosci.4913-06.2007.Peer-Reviewed Original ResearchConceptsStriatal-enriched protein tyrosine phosphataseERK/MAPK activationProtein tyrosine phosphataseCell deathTyrosine phosphataseExtracellular signal-regulated kinase/mitogen-activated protein kinase pathwayKinase/mitogen-activated protein kinase pathwayMAPK activationMAPK pathwayERK/MAPK signalingMitogen-activated protein kinase pathwayStriatal enriched protein tyrosine phosphataseProtein kinase pathwayNeuroprotective responseKinase pathwayImmediate early gene expressionKey regulatorMAPK signalingGene expressionMolecular mechanismsVivo disruptionSignificant rescuePathwayPhosphataseActivation
2005
Regulation of NMDA receptor trafficking by amyloid-β
Snyder EM, Nong Y, Almeida CG, Paul S, Moran T, Choi EY, Nairn AC, Salter MW, Lombroso PJ, Gouras GK, Greengard P. Regulation of NMDA receptor trafficking by amyloid-β. Nature Neuroscience 2005, 8: 1051-1058. PMID: 16025111, DOI: 10.1038/nn1503.Peer-Reviewed Original ResearchMeSH KeywordsAlpha7 Nicotinic Acetylcholine ReceptorAlzheimer DiseaseAmyloid beta-PeptidesAmyloid beta-Protein PrecursorAnimalsCalcineurinCell MembraneCerebral CortexCREB-Binding ProteinDisease Models, AnimalElectric ConductivityEndocytosisEnzyme ActivationMiceNeuronsN-MethylaspartateNuclear ProteinsPeptide FragmentsProtein TransportProtein Tyrosine PhosphatasesProtein Tyrosine Phosphatases, Non-ReceptorReceptors, NicotinicReceptors, N-Methyl-D-AspartateSignal TransductionSynapsesTrans-ActivatorsConceptsNMDA receptorsCortical neuronsAlzheimer's diseaseBrains of patientsAlzheimer's disease pathologyNMDA receptor traffickingGenetic mouse modelsΓ-secretase inhibitorApplication of amyloidSurface NMDA receptorsGlutamatergic transmissionSynaptic dysfunctionPersistent depressionTyrosine phosphatase STEPNicotinic receptorsMouse modelDisease processSynaptic plasticityDisease pathologyNeuronsReceptorsAmyloidSurface expressionUnderlying mechanismReceptor trafficking
2003
Receptor and nonreceptor protein tyrosine phosphatases in the nervous system
Paul S, Lombroso P. Receptor and nonreceptor protein tyrosine phosphatases in the nervous system. Cellular And Molecular Life Sciences 2003, 60: 2465-2482. PMID: 14625689, PMCID: PMC11138652, DOI: 10.1007/s00018-003-3123-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrainHumansIntracellular Signaling Peptides and ProteinsMitogen-Activated Protein KinasesNerve Tissue ProteinsProtein Tyrosine Phosphatase, Non-Receptor Type 11Protein Tyrosine Phosphatase, Non-Receptor Type 6Protein Tyrosine PhosphatasesProtein Tyrosine Phosphatases, Non-ReceptorReceptor-Like Protein Tyrosine Phosphatases, Class 2Receptor-Like Protein Tyrosine Phosphatases, Class 5Receptors, Cell SurfaceSignal TransductionConceptsProtein tyrosineNonreceptor protein tyrosineDual-specific phosphataseCellular signaling pathwaysNervous systemSignaling pathwaysCellular localizationPhysiological functionsFunctional rolePTPCentral nervous systemIntracellular mechanismsTyrosineImportant rolePhosphatasePathwayRoleLocalizationFunctionReceptors
2000
The Dopamine/D1 Receptor Mediates the Phosphorylation and Inactivation of the Protein Tyrosine Phosphatase STEP via a PKA-Dependent Pathway
Paul S, Snyder G, Yokakura H, Picciotto M, Nairn A, Lombroso P. The Dopamine/D1 Receptor Mediates the Phosphorylation and Inactivation of the Protein Tyrosine Phosphatase STEP via a PKA-Dependent Pathway. Journal Of Neuroscience 2000, 20: 5630-5638. PMID: 10908600, PMCID: PMC6772528, DOI: 10.1523/jneurosci.20-15-05630.2000.Peer-Reviewed Original ResearchMeSH KeywordsAdenosine TriphosphateAnimalsCatalytic DomainCorpus StriatumCyclic AMP-Dependent Protein KinasesEnzyme ActivationIn Vitro TechniquesMaleMolecular Sequence DataNeuronsPhosphoproteinsPhosphorus RadioisotopesPhosphorylationProtein Tyrosine PhosphatasesProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleyReceptors, Dopamine D1Signal TransductionConceptsProtein tyrosine phosphatase familyCAMP-dependent protein kinaseTryptic phosphopeptide mappingPotential phosphorylation sitesUnique N-terminalProtein-protein interactionsMembrane-associated proteinsRole of phosphorylationTyrosine phosphatase familyAmino acid sequenceSite-directed mutagenesisAmino acid sequencingPKA-dependent pathwayTyrosine phosphatase STEPPhosphatase familyPhosphopeptide mappingPhosphorylation sitesAlternative splicingSubcellular compartmentsProtein kinaseTerminal domainEquivalent residuesCytosolic proteinsSpecific residuesAcid sequence
1999
Hypoxia‐Ischemia in Perinatal Rat Brain Induces the Formation of a Low Molecular Weight Isoform of Striatal Enriched Tyrosine Phosphatase (STEP)
Gurd J, Bissoon N, Nguyen T, Lombroso P, Rider C, Beesley P, Vannucci S. Hypoxia‐Ischemia in Perinatal Rat Brain Induces the Formation of a Low Molecular Weight Isoform of Striatal Enriched Tyrosine Phosphatase (STEP). Journal Of Neurochemistry 1999, 73: 1990-1994. PMID: 10537057, DOI: 10.1046/j.1471-4159.1999.01990.x.Peer-Reviewed Original ResearchMeSH KeywordsAgingAnimalsFemaleHypoxia-Ischemia, BrainIsoenzymesMolecular WeightProtein Tyrosine PhosphatasesProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, WistarConceptsHypoxia-ischemiaP21 ratsRat brainIschemia-induced elevationP21 rat brainUnilateral hypoxia-ischemiaCerebral hypoxia-ischemiaPerinatal rat brainResult of ischemiaCalcium-dependent proteolysisLow molecular weight isoformsInterval of recoveryP7 ratsContralateral sideMolecular weight isoformsNT2/D1 cellsCalcium ionophoreLow Mr isoformPostsynaptic densityRatsBrainCalpain IWeight isoformsIschemiaPhosphorylation levels