2015
Regulation 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 neuronsStriatal‐enriched protein tyrosine phosphatase regulates the PTPα/Fyn signaling pathway
Xu J, Kurup P, Foscue E, Lombroso PJ. Striatal‐enriched protein tyrosine phosphatase regulates the PTPα/Fyn signaling pathway. Journal Of Neurochemistry 2015, 134: 629-641. PMID: 25951993, PMCID: PMC4516628, DOI: 10.1111/jnc.13160.Peer-Reviewed Original ResearchConceptsProtein tyrosine phosphataseProtein kinase ARegulation of FynTyrosine phosphataseReceptor-type protein tyrosine phosphatase alphaProtein tyrosine phosphatase alphaStriatal-enriched protein tyrosine phosphataseRegulatory tyrosine residuesActivation of FynTyrosine kinase FynRegulatory tyrosineProtein tyrosinePTPαKinase FynSynaptic membranesKinase ATyrosine residuesFyn activityFynNovel substratePrimary neuronal culturesSTEP61Synergistic regulationMolecular techniquesNovel mechanismSTEP61 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
2013
Striatal-Enriched Protein Tyrosine Phosphatase—STEPs Toward Understanding Chronic Stress-Induced Activation of Corticotrophin Releasing Factor Neurons in the Rat Bed Nucleus of the Stria Terminalis
Dabrowska J, Hazra R, Guo JD, Li C, DeWitt S, Xu J, Lombroso PJ, Rainnie DG. Striatal-Enriched Protein Tyrosine Phosphatase—STEPs Toward Understanding Chronic Stress-Induced Activation of Corticotrophin Releasing Factor Neurons in the Rat Bed Nucleus of the Stria Terminalis. Biological Psychiatry 2013, 74: 817-826. PMID: 24012328, PMCID: PMC3818357, DOI: 10.1016/j.biopsych.2013.07.032.Peer-Reviewed Original ResearchConceptsStriatal-enriched protein tyrosine phosphataseLong-term potentiationProtein tyrosine phosphataseCRF neuronsReverse transcriptase-polymerase chain reactionTranscriptase-polymerase chain reactionRestraint stressTyrosine phosphatasePolymerase chain reactionBed nucleusFactor neuronsStria terminalisWhole-cell patch-clamp electrophysiologyInduction of LTPRole of STEPQuantitative reverse transcriptase-polymerase chain reactionChain reactionNovel treatment strategiesStress-induced anxiety disordersAnxiety-like behaviorSingle-cell reverse transcriptase-polymerase chain reactionPatch-clamp electrophysiologyStress-Induced ActivationRat bed nucleusTyrosine phosphatase STEP
2010
Aβ-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