2023
Proteome-wide screening for mitogen-activated protein kinase docking motifs and interactors
Shi G, Song C, Torres Robles J, Salichos L, Lou H, Lam T, Gerstein M, Turk B. Proteome-wide screening for mitogen-activated protein kinase docking motifs and interactors. Science Signaling 2023, 16: eabm5518. PMID: 36626580, PMCID: PMC9995140, DOI: 10.1126/scisignal.abm5518.Peer-Reviewed Original ResearchConceptsMitogen-activated protein kinaseDocking motifSequence motifsDocking sequenceShort linear sequence motifsLinear sequence motifsSubstrate recruitmentHuman proteomeProtein kinaseCatalytic cleftExchange mutantsEssential functionsCultured cellsScreening pipelineWide screeningInteractorsMotifSequenceLimited repertoireSelective bindingInteractomeCombinatorial librariesMKK6ProteomeMKK7
2022
Sex- and estrous-cycle dependent dorsal hippocampal phosphoproteomic changes induced by low-dose ketamine
Saland SK, Wilczak K, Voss E, Lam TT, Kabbaj M. Sex- and estrous-cycle dependent dorsal hippocampal phosphoproteomic changes induced by low-dose ketamine. Scientific Reports 2022, 12: 1820. PMID: 35110693, PMCID: PMC8810966, DOI: 10.1038/s41598-022-05937-x.Peer-Reviewed Original ResearchConceptsLow-dose ketamineFemale ratsMale ratsTherapeutic effectIntact adult male ratsNMDA receptor antagonist ketamineAcute low doseKetamine's therapeutic effectsRapid antidepressant actionsAdult male ratsKetamine-induced changesRapid actionAntidepressant actionAntidepressant ketamineHormonal milieuHormone-dependent modulationHormonal statusLow doseKetamineBrain regionsRatsSynaptic signalingPathway activationBi-directional effectsCritical modulator
2019
Phosphorylation of human placental aromatase CYP19A1.
Ghosh D, Egbuta C, Kanyo J, Lam TT. Phosphorylation of human placental aromatase CYP19A1. Biochemical Journal 2019, 476: 3313-3331. PMID: 31652308, PMCID: PMC7069221, DOI: 10.1042/bcj20190633.Peer-Reviewed Original ResearchConceptsAromatase CYP19A1Protein-level regulationPhosphorylation/dephosphorylationMultiple phosphorylation sitesNon-genomic signaling pathwaysPost-translational modificationsNon-genomic signalingTranscriptional activatorPhosphorylation sitesProline residuesSignaling pathwaysHistidine residuesPhosphorylationLevel regulationAromatase inhibitor resistanceInhibitor resistanceMembrane interfaceRegulationReproductive systemStructural dataAromatase activityActive siteResiduesGenotoxic effectsSynaptic terminalsA single phosphoacceptor residue in BGLF3 is essential for transcription of Epstein-Barr virus late genes
Li J, Walsh A, Lam TT, Delecluse HJ, El-Guindy A. A single phosphoacceptor residue in BGLF3 is essential for transcription of Epstein-Barr virus late genes. PLOS Pathogens 2019, 15: e1007980. PMID: 31461506, PMCID: PMC6713331, DOI: 10.1371/journal.ppat.1007980.Peer-Reviewed Original ResearchConceptsPost-translational modificationsLate gene expressionLate genesGene expressionPhosphoacceptor residuesPre-initiation complexPotential phosphorylation sitesViral DNA replicationNew virus particlesEarly gene expressionPhosphorylation sitesVirus particlesDNA replicationTATA boxHerpesvirus proteinsEctopic expressionTrimeric complexLate proteinsLate transcriptsHost cellsEarly proteinsGenesTranscriptionLate kineticsProtein
2018
Phosphoproteomic analysis of cocaine memory extinction and reconsolidation in the nucleus accumbens
Torregrossa MM, MacDonald M, Stone KL, Lam TT, Nairn AC, Taylor JR. Phosphoproteomic analysis of cocaine memory extinction and reconsolidation in the nucleus accumbens. Psychopharmacology 2018, 236: 531-543. PMID: 30411139, PMCID: PMC6374162, DOI: 10.1007/s00213-018-5071-9.Peer-Reviewed Original ResearchMeSH KeywordsAmygdalaAnimalsAssociation LearningBasolateral Nuclear ComplexCocaine-Related DisordersCuesExtinction, PsychologicalMaleMental RecallMotivationNucleus AccumbensPhosphoproteinsPhosphorylationProteomicsRatsRats, Sprague-DawleyReceptors, GABA-BRecurrenceSelf AdministrationSignal TransductionConceptsCocaine-cue memoriesCue memoryCue extinctionDifferent memory processesBasolateral amygdalaCocaine-associated cuesSelf-administer cocaineNucleus accumbensBrief cueLikelihood of relapseDrug cuesAudiovisual cuesCue presentationMemory extinctionMemory processesMotivational propertiesReconsolidationCuesMemoryBehavioral conditionsMethodsMale Sprague–Dawley ratsProtein phosphorylationObjectivesThe purposeImportant research goalCross-region analysis
2017
MELK Promotes Melanoma Growth by Stimulating the NF-κB Pathway
Janostiak R, Rauniyar N, Lam TT, Ou J, Zhu LJ, Green MR, Wajapeyee N. MELK Promotes Melanoma Growth by Stimulating the NF-κB Pathway. Cell Reports 2017, 21: 2829-2841. PMID: 29212029, PMCID: PMC5726781, DOI: 10.1016/j.celrep.2017.11.033.Peer-Reviewed Original ResearchConceptsMaternal embryonic leucine zipper kinaseMelanoma growthSkin cancer-related deathsMelanoma cellsNF-κB pathway activityMAPK pathwayCancer-related deathNF-κB pathwayEmbryonic leucine zipper kinaseLeucine zipper kinaseMELK knockdownCurrent therapiesMELK inhibitionImportant downstream mediatorShort-term benefitsPharmacological inhibitionTranscription factor E2F1Downstream mediatorBRAFV600E inhibitorsSequestosome 1Pathway activityMELK functionMediatorsCell culturesInhibitionMycobacterium tuberculosis universal stress protein Rv2623 interacts with the putative ATP binding cassette (ABC) transporter Rv1747 to regulate mycobacterial growth
Glass LN, Swapna G, Chavadi SS, Tufariello JM, Mi K, Drumm JE, Lam TT, Zhu G, Zhan C, Vilchéze C, Arcos J, Chen Y, Bi L, Mehta S, Porcelli SA, Almo SC, Yeh SR, Jacobs WR, Torrelles JB, Chan J. Mycobacterium tuberculosis universal stress protein Rv2623 interacts with the putative ATP binding cassette (ABC) transporter Rv1747 to regulate mycobacterial growth. PLOS Pathogens 2017, 13: e1006515. PMID: 28753640, PMCID: PMC5549992, DOI: 10.1371/journal.ppat.1006515.Peer-Reviewed Original ResearchConceptsPutative ATP-binding cassette transporterCassette transportersATP-binding cassette (ABC) transportersProtein-protein interactionsNon-phosphorylatable alanineVivo growth phenotypesHost-pathogen interactionsCell envelope componentsAffinity chromatography experimentsFHA domainPhosphorylated threonineMutant displaysTwo-hybridGrowth phenotypePutative ATPProtein modulesMutant proteinsPhosphorylated residuesMycobacterial growthBiological processesInositol mannosidesPIM expressionTransportersInteractsEnvelope componentsBrain Region and Isoform-Specific Phosphorylation Alters Kalirin SH2 Domain Interaction Sites and Calpain Sensitivity
Miller MB, Yan Y, Machida K, Kiraly DD, Levy AD, Wu YI, Lam TT, Abbott T, Koleske AJ, Eipper BA, Mains RE. Brain Region and Isoform-Specific Phosphorylation Alters Kalirin SH2 Domain Interaction Sites and Calpain Sensitivity. ACS Chemical Neuroscience 2017, 8: 1554-1569. PMID: 28418645, PMCID: PMC5517348, DOI: 10.1021/acschemneuro.7b00076.Peer-Reviewed Original ResearchConceptsLong-term potentiationCalpain sensitivityEffects of cocaineRat nucleus accumbensAdult rat nucleus accumbensRho GDP/GTP exchange factorRegion-specific effectsChronic cocaineNucleus accumbensSynaptic functionBrain regionsKALRN geneSpine morphologyPrefrontal cortexKal7CocainePotentiationFunctional significanceCalpainPhosphorylationRice calcium‐dependent protein kinase OsCPK17 targets plasma membrane intrinsic protein and sucrose‐phosphate synthase and is required for a proper cold stress response
Almadanim MC, Alexandre BM, Rosa MTG, Sapeta H, Leitão AE, Ramalho JC, Lam TT, Negrão S, Abreu IA, Oliveira MM. Rice calcium‐dependent protein kinase OsCPK17 targets plasma membrane intrinsic protein and sucrose‐phosphate synthase and is required for a proper cold stress response. Plant Cell & Environment 2017, 40: 1197-1213. PMID: 28102545, DOI: 10.1111/pce.12916.Peer-Reviewed Original ResearchConceptsCalcium-dependent protein kinaseCold stress responseStress responsePlasma membrane intrinsic proteinsMembrane intrinsic proteinsPlant tolerance mechanismsStress-inducible genesSucrose-phosphate synthaseIntrinsic proteinsPhosphoproteomic approachCalcium-dependent mannerOsCPK17Kinase assaysSignal transductionProtein kinaseRice linesNitrogen metabolismSugar metabolismOsmotic regulationGene expressionTolerance mechanismsKey messengerMembrane channelsMost membersDirect interaction
2016
Phosphoproteomic Analysis Reveals a Novel Mechanism of CaMKIIα Regulation Inversely Induced by Cocaine Memory Extinction versus Reconsolidation
Rich MT, Abbott TB, Chung L, Gulcicek EE, Stone KL, Colangelo CM, Lam TT, Nairn AC, Taylor JR, Torregrossa MM. Phosphoproteomic Analysis Reveals a Novel Mechanism of CaMKIIα Regulation Inversely Induced by Cocaine Memory Extinction versus Reconsolidation. Journal Of Neuroscience 2016, 36: 7613-7627. PMID: 27445140, PMCID: PMC4951572, DOI: 10.1523/jneurosci.1108-16.2016.Peer-Reviewed Original ResearchMeSH Keywords1-(5-Isoquinolinesulfonyl)-2-MethylpiperazineAmygdalaAnimalsBenzylaminesCalcium-Calmodulin-Dependent Protein Kinase Type 2CocaineConditioning, OperantCuesEnzyme InhibitorsExtinction, PsychologicalHEK293 CellsHumansMaleMemoryPhosphorylationProteomicsRatsRats, Sprague-DawleySelf AdministrationSerineSignal TransductionSulfonamidesConceptsRelapse-like behaviorMemory extinctionSubsequent cue-induced reinstatementAddiction treatmentDrug-associated memoriesCocaine-associated memoryCue-induced reinstatementRelapse prevention therapySelf-administer cocaineLong-term abstinenceReconsolidation disruptionAbstinence effortsAudiovisual cuesEssential therapeutic goalCocaine memoryMemory strengtheningAmygdala inhibitionDrug useReconsolidationExtinction enhancementAddictive disordersRelapse preventionMemoryCuesEnvironmental cues
2014
Angiotensin II signaling via protein kinase C phosphorylates Kelch-like 3, preventing WNK4 degradation
Shibata S, Arroyo JP, Castañeda-Bueno M, Puthumana J, Zhang J, Uchida S, Stone KL, Lam TT, Lifton RP. Angiotensin II signaling via protein kinase C phosphorylates Kelch-like 3, preventing WNK4 degradation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 15556-15561. PMID: 25313067, PMCID: PMC4217463, DOI: 10.1073/pnas.1418342111.Peer-Reviewed Original ResearchMeSH KeywordsAdaptor Proteins, Signal TransducingAmino Acid SequenceAngiotensin IIAnimalsCarrier ProteinsCell LineHumansKidneyMice, Inbred C57BLMicrofilament ProteinsMolecular Sequence DataPhosphorylationPhosphoserineProtein BindingProtein Kinase CProtein Serine-Threonine KinasesProteolysisSignal TransductionConceptsRenal salt reabsorptionAngiotensin IIVolume depletionSalt reabsorptionNormal physiologic responseProtein kinase CAII administrationBlood pressureCardiovascular diseaseGlobal burdenPhysiologic responsesCullin 3Kinase CNaCl cotransporterReabsorptionHuman genetic studiesSecretionHypertensionNormal mechanismsWNK4 degradationMissense mutationsSerine 433WNK4Inverse relationshipCultured cellsInhibitor 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 experimentsPhosphataseInhibitorsNonenzymatic domains of Kalirin7 contribute to spine morphogenesis through interactions with phosphoinositides and Abl
Ma XM, Miller MB, Vishwanatha KS, Gross MJ, Wang Y, Abbott T, Lam TT, Mains RE, Eipper BA. Nonenzymatic domains of Kalirin7 contribute to spine morphogenesis through interactions with phosphoinositides and Abl. Molecular Biology Of The Cell 2014, 25: 1458-1471. PMID: 24600045, PMCID: PMC4004595, DOI: 10.1091/mbc.e13-04-0215.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCalpainCells, CulturedDendritic SpinesGuanine Nucleotide Exchange FactorsHippocampusMice, KnockoutNeuronsOncogene Proteins v-ablPeptide FragmentsPhosphatidylinositolsPhosphorylationProtein Processing, Post-TranslationalProtein Structure, TertiaryProteolysisRats, Sprague-DawleySynapsesTransferrinConceptsGDP/GTP exchange factorSec14 domainSpectrin repeatsSpine morphogenesisNon-receptor tyrosine kinaseGTP exchange factorSpine formationNatural splice variantSpectrin repeat domainReceptor-mediated endocytosisRho GDP/GTP exchange factorDrosophila orthologueMembrane traffickingPhosphomimetic mutationExchange factorCalpain-mediated degradationRepeat domainTruncation mutantsTyrosine kinaseGenetic studiesCellular membranesSplice variantsRepeatsNonneuronal cellsMorphogenesis
2013
Assembly of the SLIP1–SLBP Complex on Histone mRNA Requires Heterodimerization and Sequential Binding of SLBP Followed by SLIP1
Bansal N, Zhang M, Bhaskar A, Itotia P, Lee E, Shlyakhtenko LS, Lam TT, Fritz A, Berezney R, Lyubchenko YL, Stafford WF, Thapar R. Assembly of the SLIP1–SLBP Complex on Histone mRNA Requires Heterodimerization and Sequential Binding of SLBP Followed by SLIP1. Biochemistry 2013, 52: 520-536. PMID: 23286197, PMCID: PMC3580866, DOI: 10.1021/bi301074r.Peer-Reviewed Original ResearchCarrier ProteinsHistonesHumansKineticsMRNA Cleavage and Polyadenylation FactorsMutagenesis, Site-DirectedMutant ProteinsNuclear ProteinsPeptide FragmentsPhosphorylationPoint MutationProtein BindingProtein Interaction Domains and MotifsProtein MultimerizationProtein Processing, Post-TranslationalRecombinant ProteinsRNA FoldingRNA-Binding ProteinsRNA, MessengerSerineThreonineTyrosine
2012
Interaction of the Histone mRNA Hairpin with Stem–Loop Binding Protein (SLBP) and Regulation of the SLBP–RNA Complex by Phosphorylation and Proline Isomerization
Zhang M, Lam TT, Tonelli M, Marzluff WF, Thapar R. Interaction of the Histone mRNA Hairpin with Stem–Loop Binding Protein (SLBP) and Regulation of the SLBP–RNA Complex by Phosphorylation and Proline Isomerization. Biochemistry 2012, 51: 3215-3231. PMID: 22439849, PMCID: PMC3328597, DOI: 10.1021/bi2018255.Peer-Reviewed Original ResearchConceptsStem-loop binding proteinStem-loop structureHistone mRNAProline isomerizationThreonine phosphorylationEnd formationC base pairsReplication-dependent histone mRNAsBase pairsBinding proteinPossible structural roleAdjacent prolineHistone proteinsRibonucleoprotein complexesHelix motifMRNA hairpinsMRNA complexesUntranslated regionStructural roleFirst binding sitePhosphorylationProteinComplex dissociationCritical hingeMRNA