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 ResearchConceptsIschemic 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 disorders
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
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 ResearchConceptsStriatal-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
2006
The Striatal-Enriched Protein Tyrosine Phosphatase Gates Long-Term Potentiation and Fear Memory in the Lateral Amygdala
Paul S, Olausson P, Venkitaramani DV, Ruchkina I, Moran TD, Tronson N, Mills E, Hakim S, Salter MW, Taylor JR, Lombroso PJ. The Striatal-Enriched Protein Tyrosine Phosphatase Gates Long-Term Potentiation and Fear Memory in the Lateral Amygdala. Biological Psychiatry 2006, 61: 1049-1061. PMID: 17081505, PMCID: PMC1853327, DOI: 10.1016/j.biopsych.2006.08.005.Peer-Reviewed Original ResearchMeSH KeywordsAcoustic StimulationAminoacetonitrileAmygdalaAnimalsBehavior, AnimalCells, CulturedConditioning, ClassicalCycloheximideElectric StimulationEnzyme InhibitorsFearFemaleImmunohistochemistryIn Vitro TechniquesLong-Term PotentiationMemoryMitogen-Activated Protein Kinase 1Mitogen-Activated Protein Kinase 3NeostriatumPatch-Clamp TechniquesPoint MutationPregnancyProtein Synthesis InhibitorsProtein Tyrosine PhosphatasesRatsRats, Sprague-DawleyTranslocation, GeneticConceptsStriatal-enriched protein tyrosine phosphataseERK1/2 activationMitogen-activated protein kinaseProtein tyrosine phosphataseDe novo translationActivation of ERK1/2Tyrosine phosphataseProtein bindsKinase signalingProtein kinaseSequential recruitmentAmygdala-dependent memory formationERK pathwayMemory formationPrimary cell culturesNuclear translocationBiphasic activationLong-term potentiationTranslation blockTAT-STEPERKCell culturesERK1/2ActivationPathway