2015
Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice
Xu J, Kurup P, Baguley TD, Foscue E, Ellman JA, Nairn AC, Lombroso PJ. Inhibition of the tyrosine phosphatase STEP61 restores BDNF expression and reverses motor and cognitive deficits in phencyclidine-treated mice. Cellular And Molecular Life Sciences 2015, 73: 1503-1514. PMID: 26450419, PMCID: PMC4801664, DOI: 10.1007/s00018-015-2057-1.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzothiepinsBrain-Derived Neurotrophic FactorCells, CulturedCognition DisordersCREB-Binding ProteinDown-RegulationMaleMiceMice, Inbred C57BLMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3Motor ActivityNeuronsPhencyclidinePhosphorylationProtein Tyrosine PhosphatasesReceptors, N-Methyl-D-AspartateRNA InterferenceUbiquitinationConceptsBrain-derived neurotrophic factorBDNF expressionProtein tyrosine Phosphatase 61Cognitive deficitsPCP-induced reductionPCP-treated micePhencyclidine-treated micePCP-induced increasePCP-induced hyperlocomotionTyrosine phosphatase STEP61STEP61 levelsBDNF transcriptionNeurotrophic factorNMDAR antagonistsCortical culturesCortical neuronsCNS disordersSynaptic strengtheningPsychotic episodeRodent modelsBrain disordersPharmacologic inhibitionSTEP61SchizophreniaCognitive functioningRegulation of STEP61 and tyrosine-phosphorylation of NMDA and AMPA receptors during homeostatic synaptic plasticity
Jang SS, Royston SE, Xu J, Cavaretta JP, Vest MO, Lee KY, Lee S, Jeong HG, Lombroso PJ, Chung HJ. Regulation of STEP61 and tyrosine-phosphorylation of NMDA and AMPA receptors during homeostatic synaptic plasticity. Molecular Brain 2015, 8: 55. PMID: 26391783, PMCID: PMC4578242, DOI: 10.1186/s13041-015-0148-4.Peer-Reviewed Original ResearchConceptsN-methyl-D-aspartate receptorsHomeostatic synaptic plasticitySynaptic plasticityTyrosine phosphorylationActivity blockadeDephosphorylation of GluN2BSynaptic scalingProtein tyrosine phosphataseLevel of GluN2BProlonged activity blockadeExcitatory synaptic transmissionHippocampal cultured neuronsIsoxazolepropionic acid (AMPA) receptorsNMDAR subunit GluN2BActivity-dependent regulationTyrosine phosphataseSTEP61 levelsHomeostatic stabilizationSynaptic transmissionExcitatory synapsesAMPA receptorsGluA2 expressionPostsynaptic accumulationCultured neuronsAcid receptorsDown‐regulation of BDNF in cell and animal models increases striatal‐enriched protein tyrosine phosphatase 61 (STEP61) levels
Xu J, Kurup P, Azkona G, Baguley TD, Saavedra A, Nairn AC, Ellman JA, Pérez-Navarro E, Lombroso PJ. Down‐regulation of BDNF in cell and animal models increases striatal‐enriched protein tyrosine phosphatase 61 (STEP61) levels. Journal Of Neurochemistry 2015, 136: 285-294. PMID: 26316048, PMCID: PMC4769989, DOI: 10.1111/jnc.13295.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBenzothiepinsBrainBrain-Derived Neurotrophic FactorCells, CulturedCysteine Proteinase InhibitorsDown-RegulationEmbryo, MammalianFemaleFlavonesLeupeptinsMaleMiceMice, Inbred C57BLMice, TransgenicMotor ActivityNeuronsProtein Tyrosine PhosphatasesRatsRats, Sprague-DawleyRNA, Small InterferingTime FactorsConceptsBrain-derived neurotrophic factorNormal cognitive functionSynaptic strengtheningStriatal-enriched protein tyrosine phosphataseBDNF expressionBDNF knockdownCortical culturesRegulation of BDNFN-methyl-D-aspartate receptor functionNeuropsychiatric disordersCognitive functionBetter therapeutic strategiesMouse frontal cortexNMDA receptor subunit GluN2BSTEP61 levelsHyperlocomotor activityMotor abnormalitiesNeurotrophic factorNMDA receptorsFrontal cortexKinase B signalingTherapeutic strategiesAgonists resultsAnimal modelsCultured neuronsBDNF Induces Striatal-Enriched Protein Tyrosine Phosphatase 61 Degradation Through the Proteasome
Saavedra A, Puigdellívol M, Tyebji S, Kurup P, Xu J, Ginés S, Alberch J, Lombroso PJ, Pérez-Navarro E. BDNF Induces Striatal-Enriched Protein Tyrosine Phosphatase 61 Degradation Through the Proteasome. Molecular Neurobiology 2015, 53: 4261-4273. PMID: 26223799, PMCID: PMC4738169, DOI: 10.1007/s12035-015-9335-7.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain-Derived Neurotrophic FactorCerebral CortexExtracellular Signal-Regulated MAP KinasesHippocampusMembrane PotentialsMiceNeostriatumNerve Growth FactorNeuronsNeurotrophin 3Phospholipase C gammaPhosphorylationProteasome Endopeptidase ComplexProtein Tyrosine Phosphatases, Non-ReceptorProteolysisReceptors, N-Methyl-D-AspartateUbiquitinationConceptsBrain-derived neurotrophic factorSTEP61 levelsCortical neuronsUbiquitin-proteasome systemStriatal-enriched protein tyrosine phosphatasePrimary cortical neuronsLevels/activitiesNerve growth factorNeurotrophic factorNeurotrophin-3Cultured striatalHippocampal neuronsCell depolarizationGrowth factorERK1/2 phosphorylationNeuronsStriatalTyrosine kinasePhospholipase C-gammaC gammaDifferent mechanismsLevelsBlockadeGluN2BProtein tyrosine phosphataseSTEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson’s disease
Kurup PK, Xu J, Videira RA, Ononenyi C, Baltazar G, Lombroso PJ, Nairn AC. STEP61 is a substrate of the E3 ligase parkin and is upregulated in Parkinson’s disease. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 1202-1207. PMID: 25583483, PMCID: PMC4313846, DOI: 10.1073/pnas.1417423112.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCorpus StriatumCyclic AMP Response Element-Binding ProteinDown-RegulationGene Expression Regulation, EnzymologicHEK293 CellsHumansMAP Kinase Signaling SystemMiceMice, KnockoutMitogen-Activated Protein Kinase 3MPTP PoisoningProtein Tyrosine Phosphatases, Non-ReceptorRatsRats, Sprague-DawleyUbiquitinationUbiquitin-Protein LigasesUp-RegulationConceptsE3 ubiquitin ligase ParkinSubstantia nigra pars compactaPathophysiology of PDProtein tyrosine phosphataseUbiquitin ligase ParkinSporadic Parkinson's diseaseE3 ligase ParkinRegulation of ParkinParkinson's diseaseTyrosine phosphataseParkin mutantsE3 ligaseProteasome systemDopaminergic neuronsDownstream targetsAutosomal recessive juvenile parkinsonismNovel substrateSTEP61ParkinCellular modelSTEP61 levelsSNc dopaminergic neuronsProtein levelsFunction contributesERK1/2
2014
Alterations in STriatal‐Enriched protein tyrosine Phosphatase expression, activation, and downstream signaling in early and late stages of the YAC128 Huntington's disease mouse model
Gladding CM, Fan J, Zhang LY, Wang L, Xu J, Li EH, Lombroso PJ, Raymond LA. Alterations in STriatal‐Enriched protein tyrosine Phosphatase expression, activation, and downstream signaling in early and late stages of the YAC128 Huntington's disease mouse model. Journal Of Neurochemistry 2014, 130: 145-159. PMID: 24588402, PMCID: PMC4065618, DOI: 10.1111/jnc.12700.Peer-Reviewed Original ResearchConceptsDisease mouse modelYAC128 Huntington's disease mouse modelHuntington's disease mouse modelYAC128 miceCalpain-mediated cleavageMitogen-activated protein kinaseMouse modelCalpain inhibitionProtein tyrosine Phosphatase 61Wild-type cortical neuronsP38 phosphorylationNMDA receptor traffickingSTEP61 levelsSynaptic dysfunctionNMDAR localizationP38 mitogen-activated protein kinaseStriatal apoptosisCortical neuronsExtracellular signal-regulated proteinApoptotic signalingMutant huntingtin proteinStriatal tissueStriatal neurodegenerationTransgenic miceCalcium homeostasis
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 plasticity