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
1997
STEP: a family of brain-enriched PTPs. Alternative splicing produces transmembrane, cytosolic and truncated isoforms.
Bult A, Zhao F, Dirkx R, Raghunathan A, Solimena M, Lombroso P. STEP: a family of brain-enriched PTPs. Alternative splicing produces transmembrane, cytosolic and truncated isoforms. European Journal Of Cell Biology 1997, 72: 337-44. PMID: 9127733.Peer-Reviewed Original ResearchMeSH KeywordsAlternative SplicingAmino Acid SequenceAnimalsBase SequenceBlotting, NorthernBlotting, WesternBrainCalcium-Binding ProteinsCalnexinCHO CellsCricetinaeFemaleFluorescent Antibody Technique, IndirectMembrane ProteinsMolecular Sequence DataProtein Tyrosine PhosphatasesProtein Tyrosine Phosphatases, Non-ReceptorRatsSynaptophysinTransfectionConceptsProtein tyrosine phosphataseCatalytic phosphatase domainProtein tyrosine kinase familyHydrophobic amino acid sequenceAlternative splicing mechanismAmino acid sequencePrevious biochemical studiesTyrosine kinase familyStop codon upstreamPhosphatase domainCytosolic variantAlternative splicingMembrane compartmentsTyrosine phosphataseKinase familySplicing mechanismSubcellular localizationCytosolic proteinsAcid sequenceN-terminusInactive variantContinuous sucrose gradientSTEP isoformsPolyproline domainEndoplasmic reticulum
1996
STEP61: A Member of a Family of Brain-Enriched PTPs Is Localized to the Endoplasmic Reticulum
Bult A, Zhao F, Dirkx R, Sharma E, Lukacsi E, Solimena M, Naegele J, Lombroso P. STEP61: A Member of a Family of Brain-Enriched PTPs Is Localized to the Endoplasmic Reticulum. Journal Of Neuroscience 1996, 16: 7821-7831. PMID: 8987810, PMCID: PMC6579237, DOI: 10.1523/jneurosci.16-24-07821.1996.Peer-Reviewed Original ResearchConceptsNovel N-terminal regionEnzymatic activityEndoplasmic reticulumPutative transmembrane domainsIntrinsic membrane proteinsExtended N-terminusAmino acid sequenceN-terminal regionDistinctive intracellular distributionsProtein tyrosineCytosolic variantTransmembrane domainMembrane compartmentsMembrane proteinsAcid sequenceSubcellular fractionationN-terminusRecombinant proteinsTransfection experimentsSTEP61Intracellular distributionProteinReticulumImmunocytochemical labelingFamily
1995
Identification of two alternatively spliced transcripts of STEP: a subfamily of brain-enriched protein tyrosine phosphatases
Sharma E, Zhao F, Bult A, Lombroso P. Identification of two alternatively spliced transcripts of STEP: a subfamily of brain-enriched protein tyrosine phosphatases. Brain Research 1995, 32: 87-93. PMID: 7494467, DOI: 10.1016/0169-328x(95)00066-2.Peer-Reviewed Original ResearchConceptsTyrosine phosphatase domainPhosphatase domainProtein tyrosineSpliced transcriptsExon-intron organizationProtein tyrosine phosphataseOpen reading frameTyrosine phosphataseReading frameDistinct functionsGenomic DNANorthern analysisSTEP geneSTEP isoformsMolecular massTranscriptsSTEP61ProteinMouse brainTyrosineCentral nervous systemSubfamiliesGenesNervous systemMonoclonal antibodiesA Neuronal Protein Tyrosine Phosphatase Induced by Nerve Growth Factor (∗)
Sharma E, Lombroso P. A Neuronal Protein Tyrosine Phosphatase Induced by Nerve Growth Factor (∗). Journal Of Biological Chemistry 1995, 270: 49-53. PMID: 7814416, DOI: 10.1074/jbc.270.1.49.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsBase SequenceDNAEnzyme InductionIntracellular Signaling Peptides and ProteinsMolecular Sequence DataNerve Growth FactorsNerve Tissue ProteinsNeuronsPC12 CellsProtein Tyrosine PhosphatasesRatsReceptor-Like Protein Tyrosine Phosphatases, Class 7Recombinant Fusion ProteinsSequence Homology, Amino AcidConceptsNerve growth factorNGF treatmentGrowth factorNon-receptor protein tyrosine phosphataseRat brainNeuronal growthProtein tyrosine phosphataseMRNA levelsBrainNorthern blot analysisPC12 cellsBlot analysisTyrosine phosphataseTreatmentPhosphataseExpressionFusion proteinTyrosine phosphatase activity
1991
Molecular characterization of a protein-tyrosine-phosphatase enriched in striatum.
Lombroso P, Murdoch G, Lerner M. Molecular characterization of a protein-tyrosine-phosphatase enriched in striatum. Proceedings Of The National Academy Of Sciences Of The United States Of America 1991, 88: 7242-7246. PMID: 1714595, PMCID: PMC52270, DOI: 10.1073/pnas.88.16.7242.Peer-Reviewed Original ResearchConceptsDeduced amino acid sequenceAmino acid consensus sequenceAmino acid sequenceApparent molecular massRat striatal cDNA librarySingle geneVitro translationCDNA clonesStrong homologyCDNA libraryCytoplasmic membraneAcid sequenceRNA transcriptsN-terminusMolecular characterizationRNA analysisMolecular massAmino acidsProteinPhosphataseMRNASequenceHomologyGenesTerminus