2015
STEP61 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
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
2012
Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation
Tautz L, Sergienko E, Xu J, Liu W, Dahl R, Critton D, Su Y, Brown B, Chan X, Yang L, Bobkova E, Vasile S, Yuan H, Rascon J, Colayco S, Sidique S, Cosford N, Chung T, Mustelin T, Page R, Lombroso P. Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation. The FASEB Journal 2012, 26: 766.12-766.12. DOI: 10.1096/fasebj.26.1_supplement.766.12.Peer-Reviewed Original ResearchHematopoietic protein tyrosine phosphataseP38 activationProtein tyrosine phosphataseUnique amino acid residuesAmino acid residuesNew drug targetsCell cycle arrestMAP kinases ERK1/2Activation of ERK1/2Tyrosine phosphataseHePTPMutagenesis experimentsMAP kinaseKinases ERK1/2Acid residuesCatalytic pocketDrug targetsTransient activationCycle arrestT-cell acute lymphoblastic leukemiaERK1/2Prolonged activationHuman T cellsPharmacological inhibitionCancer cells
2011
Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation
Sergienko E, Xu J, Liu WH, Dahl R, Critton DA, Su Y, Brown BT, Chan X, Yang L, Bobkova EV, Vasile S, Yuan H, Rascon J, Colayco S, Sidique S, Cosford ND, Chung TD, Mustelin T, Page R, Lombroso PJ, Tautz L. Inhibition of Hematopoietic Protein Tyrosine Phosphatase Augments and Prolongs ERK1/2 and p38 Activation. ACS Chemical Biology 2011, 7: 367-377. PMID: 22070201, PMCID: PMC3288537, DOI: 10.1021/cb2004274.Peer-Reviewed Original ResearchConceptsHematopoietic protein tyrosine phosphataseP38 activationMitogen-activated protein kinases ERK1/2Protein tyrosine phosphataseUnique amino acid residuesSmall molecule modulatorsProtein kinases ERK1/2Amino acid residuesRegulation of MAPKNew drug targetsCell cycle arrestTyrosine phosphataseHePTPMutagenesis experimentsKinases ERK1/2Acid residuesCatalytic pocketCell senescenceDrug targetsTransient activationCycle arrestT-cell acute lymphoblastic leukemiaHematopoietic cellsERK1/2Prolonged activation