2018
PAR3–PAR6–atypical PKC polarity complex proteins in neuronal polarization
Hapak SM, Rothlin CV, Ghosh S. PAR3–PAR6–atypical PKC polarity complex proteins in neuronal polarization. Cellular And Molecular Life Sciences 2018, 75: 2735-2761. PMID: 29696344, PMCID: PMC11105418, DOI: 10.1007/s00018-018-2828-6.BooksConceptsPar3-Par6Neuronal polarityNeuronal polarizationPolarity complex proteinsAPKC kinase activityEukaryotic cell typesProtein complexesComplex proteinsKinase activityPar6APKCSignaling mechanismCell typesPar3Effector moleculesProteinImportant roleEffector functionsPolarityComplexesFundamental featuresPathwayRoleAssemblyCellsaPKCζ-dependent Repression of Yap is Necessary for Functional Restoration of Irradiated Salivary Glands with IGF-1
Chibly AM, Wong WY, Pier M, Cheng H, Mu Y, Chen J, Ghosh S, Limesand KH. aPKCζ-dependent Repression of Yap is Necessary for Functional Restoration of Irradiated Salivary Glands with IGF-1. Scientific Reports 2018, 8: 6347. PMID: 29679075, PMCID: PMC5910385, DOI: 10.1038/s41598-018-24678-4.Peer-Reviewed Original Research
2015
PKCι interacts with Rab14 and modulates epithelial barrier function through regulation of claudin-2 levels
Lu R, Dalgalan D, Mandell EK, Parker SS, Ghosh S, Wilson JM. PKCι interacts with Rab14 and modulates epithelial barrier function through regulation of claudin-2 levels. Molecular Biology Of The Cell 2015, 26: 1523-1531. PMID: 25694446, PMCID: PMC4395131, DOI: 10.1091/mbc.e14-12-1613.Peer-Reviewed Original ResearchConceptsClaudin-2 levelsSmall GTPase Rab14Claudin-2 protein levelsClaudin-2Junction proteinsTransepithelial resistanceEpithelial polarityIntracellular punctaTight junction componentsTight junction proteinsPlasma membraneNormal assemblyRab14 expressionRab14Junction componentsPKCιKnockdownEpithelial barrier functionProtein levelsTight junctionsZO-1ProteinParacellular permeabilityClaudin-1APKC
2014
Targeting aPKC disables oncogenic signaling by both the EGFR and the proinflammatory cytokine TNFα in glioblastoma
Kusne Y, Carrera-Silva EA, Perry AS, Rushing EJ, Mandell EK, Dietrich JD, Errasti AE, Gibbs D, Berens ME, Loftus JC, Hulme C, Yang W, Lu Z, Aldape K, Sanai N, Rothlin CV, Ghosh S. Targeting aPKC disables oncogenic signaling by both the EGFR and the proinflammatory cytokine TNFα in glioblastoma. Science Signaling 2014, 7: ra75. PMID: 25118327, PMCID: PMC4486020, DOI: 10.1126/scisignal.2005196.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarcinogenesisDrug Delivery SystemsEnzyme-Linked Immunosorbent AssayEpidermal Growth FactorErbB ReceptorsErlotinib HydrochlorideFlow CytometryFluorescent Antibody TechniqueGlioblastomaHumansImmunoblottingImmunohistochemistryImmunoprecipitationKaplan-Meier EstimateMiceNF-kappa BParacrine CommunicationProtein Kinase CQuinazolinesReverse Transcriptase Polymerase Chain ReactionSignal TransductionTumor Necrosis Factor-alphaConceptsAtypical protein kinase CEpidermal growth factor receptorEGFR kinase inhibitorsHuman glioblastoma tumor cellsReceptor tyrosine kinasesProtein kinase CTNFα-dependent activationKinase inhibitorsTranscription factor nuclear factor κBGlioblastoma tumor cellsGrowth factor receptorKinase activityMolecular approachesTyrosine kinaseKinase CNuclear factor κBFactor receptorGlioblastoma microenvironmentFactor κBProinflammatory cytokine TNFαAbundanceTumor necrosis factorGlioblastoma therapyTumor growthGrade IV glioblastoma
2013
Competing molecular interactions of aPKC isoforms regulate neuronal polarity
Parker SS, Mandell EK, Hapak SM, Maskaykina IY, Kusne Y, Kim JY, Moy JK, St. John PA, Wilson JM, Gothard KM, Price TJ, Ghosh S. Competing molecular interactions of aPKC isoforms regulate neuronal polarity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 14450-14455. PMID: 23940317, PMCID: PMC3761571, DOI: 10.1073/pnas.1301588110.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell PolarityCells, CulturedFemaleHippocampusIsoenzymesNeuronsPregnancyProtein Kinase CRatsRats, Sprague-DawleyConceptsAtypical protein kinase CNeuronal polarityAPKC isoformsProtein kinase CCell polarityPolarized neuronsAlternative transcriptsKinase CPar3Supernumerary axonsIsoformsEmbryonic hippocampal neuronsMolecular interactionsOverexpressionPresumptive axonsMolecular modelHippocampal neuronsPolarityPKMTranscriptsRegulatorIntermolecular competitionInteractsNeuronsDisruptsZIPping to Pain Relief: The Role (or Not) of PKMζ in Chronicc Pain
Price TJ, Ghosh S. ZIPping to Pain Relief: The Role (or Not) of PKMζ in Chronicc Pain. Molecular Pain 2013, 9: 1744-8069-9-6. PMID: 23433248, PMCID: PMC3621284, DOI: 10.1186/1744-8069-9-6.BooksConceptsChronic pain statesChronic painLong-term potentiationAnterior cingulate cortexPain statesPain plasticityCertain chronic pain statesRole of PKMζSpinal dorsal hornChronic pain developmentSignificant clinical problemPotential roleSuch off-target effectsPain reliefDorsal hornPain developmentCNS areasCNS regionsClinical problemNociceptor stimulationPainCingulate cortexNew targetsKey moleculesOff-target effectsBDNF Regulates Atypical PKC at Spinal Synapses to Initiate and Maintain a Centralized Chronic Pain State
Melemedjian OK, Tillu DV, Asiedu MN, Mandell EK, Moy JK, Blute VM, Taylor CJ, Ghosh S, Price TJ. BDNF Regulates Atypical PKC at Spinal Synapses to Initiate and Maintain a Centralized Chronic Pain State. Molecular Pain 2013, 9: 1744-8069-9-12. PMID: 23510079, PMCID: PMC3608966, DOI: 10.1186/1744-8069-9-12.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsBrain-Derived Neurotrophic FactorCalcium-Calmodulin-Dependent Protein Kinase Type 2Cerebral CortexChronic PainEukaryotic Initiation Factor-4FExtracellular Signal-Regulated MAP KinasesMaleMAP Kinase Signaling SystemMiceMice, Inbred ICRMitogen-Activated Protein Kinase KinasesModels, BiologicalPhosphorylationPosterior Horn CellsProtein BiosynthesisProtein Kinase CProtein TransportSynapsesTime FactorsTOR Serine-Threonine KinasesConceptsChronic pain statesPain statesPersistent nociceptive sensitizationSpinal synapsesChronic painNociceptive sensitizationPotential therapeutic targetImportant medical problemNeurotrophic factorBDNF regulationPersistent sensitizationBDNFTherapeutic targetMedical problemsPainNovel therapeuticsEssential mediatorSensitizationPermanent reversalSynapsesMolecular linkPKMζKey regulator
2012
Contribution of PKMζ-dependent and independent amplification to components of experimental neuropathic pain
King T, Qu C, Okun A, Melemedjian OK, Mandell EK, Maskaykina IY, Navratilova E, Dussor GO, Ghosh S, Price TJ, Porreca F. Contribution of PKMζ-dependent and independent amplification to components of experimental neuropathic pain. Pain 2012, 153: 1263-1273. PMID: 22482911, PMCID: PMC3358498, DOI: 10.1016/j.pain.2012.03.006.Peer-Reviewed Original ResearchConceptsRostral anterior cingulate cortexExperimental neuropathic painNeuropathic painMK-801Spontaneous painN-methyl-D-aspartate receptor blockadeSpinal nerve ligation injuryNerve ligation injurySpinal dorsal hornLong-term potentiationAnterior cingulate cortexPseudosubstrate inhibitory peptideDorsal hornReceptor blockadeTime-dependent mannerLigation injuryPain processingSingle administrationSpinal cordPainCingulate cortexFull recoveryInhibitory peptidesInhibition of PKMζIndependent mechanisms
2011
Spinal Protein Kinase M ζ Underlies the Maintenance Mechanism of Persistent Nociceptive Sensitization
Asiedu MN, Tillu DV, Melemedjian OK, Shy A, Sanoja R, Bodell B, Ghosh S, Porreca F, Price TJ. Spinal Protein Kinase M ζ Underlies the Maintenance Mechanism of Persistent Nociceptive Sensitization. Journal Of Neuroscience 2011, 31: 6646-6653. PMID: 21543593, PMCID: PMC3090264, DOI: 10.1523/jneurosci.6286-10.2011.Peer-Reviewed Original ResearchConceptsLate long-term potentiationInterleukin-6Intraplantar injectionPersistent nociceptive sensitizationIntrathecal injectionNociceptive sensitizationResolution of hypersensitivitySpinal dorsal hornClinical pain disordersProtein kinase M ζLong-term potentiationAllodynic statePlantar incisionDorsal hornPain pathwaysPain statesAgonist injectionPain disordersAgonist DHPGNocifensive behaviorNocifensive responsesPKMζ inhibitorSpinal cordAllodyniaTherapeutic benefit
2008
Instructive role of aPKCζ subcellular localization in the assembly of adherens junctions in neural progenitors
Ghosh S, Marquardt T, Thaler JP, Carter N, Andrews SE, Pfaff SL, Hunter T. Instructive role of aPKCζ subcellular localization in the assembly of adherens junctions in neural progenitors. Proceedings Of The National Academy Of Sciences Of The United States Of America 2008, 105: 335-340. PMID: 18162555, PMCID: PMC2224213, DOI: 10.1073/pnas.0705713105.Peer-Reviewed Original ResearchConceptsAdherens junctionsNeural progenitorsNeural tubeApical-basal polarityCell fate determinantsNeuronal precursorsApical adherens junctionsApical membranePKCzeta/lambdaCell-cell adhesionChicken neural tubeStem cell proliferationPostmitotic neuronal precursorsAsymmetric inheritanceApical assemblyFate determinantsAsymmetric localizationNeural stem cell proliferationSubcellular compartmentalizationSubcellular localizationNeural stem cellsKinase activityInstructive signalsNeurogenic divisionsInstructive role