2012
Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrate
Ha BH, Davis MJ, Chen C, Lou HJ, Gao J, Zhang R, Krauthammer M, Halaban R, Schlessinger J, Turk BE, Boggon TJ. Type II p21-activated kinases (PAKs) are regulated by an autoinhibitory pseudosubstrate. Proceedings Of The National Academy Of Sciences Of The United States Of America 2012, 109: 16107-16112. PMID: 22988085, PMCID: PMC3479536, DOI: 10.1073/pnas.1214447109.Peer-Reviewed Original ResearchConceptsP21-activated kinasePhosphorylated activation loopActivation loop phosphorylationCritical proline residueRho family GTPasesBcl-2/BclCellular morphological changesPAK regulationStructure-guided approachLoop phosphorylationPseudosubstrate regionAutoinhibitory pseudosubstratePseudosubstrate motifActivation loopCatalytic domainSrc SH3Cell motilityMolecular basisProline residuesKey effectorsCell deathPAK4SH3KinasePseudosubstrate
2011
Phosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma
Tworkoski K, Singhal G, Szpakowski S, Zito CI, Bacchiocchi A, Muthusamy V, Bosenberg M, Krauthammer M, Halaban R, Stern DF. Phosphoproteomic Screen Identifies Potential Therapeutic Targets in Melanoma. Molecular Cancer Research 2011, 9: 801-812. PMID: 21521745, PMCID: PMC3117976, DOI: 10.1158/1541-7786.mcr-10-0512.Peer-Reviewed Original ResearchMeSH KeywordsApoptosisCell Line, TumorCell MovementCell ProliferationErbB ReceptorsGene Expression Regulation, NeoplasticGene Knockdown TechniquesHEK293 CellsHumansInfant, NewbornMelanocytesMelanomaPhosphoproteinsPhosphorylationProteomicsReceptor Protein-Tyrosine KinasesReceptor, IGF Type 2RNA, Small InterferingSignal TransductionSkin NeoplasmsSTAT3 Transcription FactorConceptsTherapeutic targetReceptor tyrosine kinasesMelanoma cellsPotential therapeutic targetIdentifies potential therapeutic targetsActive receptor tyrosine kinasesTyrosine kinaseMelanoma cell migrationReceptor expressionBreast cancerAxl knockdownAutocrine circuitTherapeutic interventionsCancer subtypesReceptor tyrosine kinase activationTyrosine kinase activationNovel targetActivated receptorsAxlRNA knockdownMelanomaCell migrationHER3KnockdownIGF1R
2003
The tyrphostin AG1024 accelerates the degradation of phosphorylated forms of retinoblastoma protein (pRb) and restores pRb tumor suppressive function in melanoma cells.
von Willebrand M, Zacksenhaus E, Cheng E, Glazer P, Halaban R. The tyrphostin AG1024 accelerates the degradation of phosphorylated forms of retinoblastoma protein (pRb) and restores pRb tumor suppressive function in melanoma cells. Cancer Research 2003, 63: 1420-9. PMID: 12649208.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Cycle ProteinsCell DivisionCyclin-Dependent KinasesDNA-Binding ProteinsE2F Transcription FactorsE2F1 Transcription FactorE2F3 Transcription FactorHumansMAP Kinase Signaling SystemMelanocytesMelanomaMiceMitogen-Activated Protein Kinase 1PhosphorylationRetinoblastoma ProteinTranscription FactorsTyrphostinsUbiquitinConceptsTumor suppressive functionPhosphorylated formCell surface receptor kinaseMitogen-activated protein kinase/extracellular signal-regulated kinase pathwayProtein kinase/extracellular signal-regulated kinase pathwayExtracellular signal-regulated kinase (ERK) pathwaySignal-regulated kinase pathwayMelanoma cellsPhosphorylation/inactivationCyclin-dependent kinase 2Insulin-like growth factor 1 receptorActivation of pRbReceptor kinase activitySpecific chemical inhibitorsGrowth factor 1 receptorFactor 1 receptorPocket proteinsRetinoblastoma familyMelanoma cell proliferationReceptor kinaseProtein degradationKinase pathwayRetinoblastoma proteinKinase activityMelanoma cell growth
2000
Deregulated E2f Transcriptional Activity in Autonomously Growing Melanoma Cells
Halaban R, Cheng E, Smicun Y, Germino J. Deregulated E2f Transcriptional Activity in Autonomously Growing Melanoma Cells. Journal Of Experimental Medicine 2000, 191: 1005-1016. PMID: 10727462, PMCID: PMC2193116, DOI: 10.1084/jem.191.6.1005.Peer-Reviewed Original ResearchMeSH KeywordsCarrier ProteinsCell Cycle ProteinsCell DivisionCells, CulturedCellular SenescenceCulture Media, ConditionedCyclin-Dependent KinasesCyclinsDNA-Binding ProteinsDown-RegulationDrosophila ProteinsE2F Transcription FactorsE2F1 Transcription FactorE2F2 Transcription FactorE2F3 Transcription FactorE2F4 Transcription FactorE2F5 Transcription FactorE2F6 Transcription FactorEnzyme InhibitorsFlavonoidsHumansMelanocytesMelanomaPhosphorylationPiperidinesProtein BindingRetinoblastoma-Binding Protein 1Trans-ActivatorsTranscription Factor DP1Transcription FactorsTumor Cells, CulturedConceptsExternal growth factorsE2F DNAPocket proteinsCyclin-dependent kinase 4Normal melanocytesTranscriptional activityRetinoblastoma tumor suppressor proteinMelanoma cellsMalignant human melanocytesE2F transcription factorsE2F family membersE2F transcriptional activityTumor suppressor proteinGel shift analysisCell cycle progressionForm of pRBGrowth factorContinuous high expressionE2F activityOnly family memberTranscription factorsProtein DNASuppressor proteinFamily membersMolecular basis
1999
Melanoma Cell Autonomous Growth: The Rb/E2F Pathway
Halaban R. Melanoma Cell Autonomous Growth: The Rb/E2F Pathway. Cancer And Metastasis Reviews 1999, 18: 333-343. PMID: 10721488, DOI: 10.1023/a:1006396104073.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCarrier ProteinsCell CycleCell Cycle ProteinsCell DivisionCyclin-Dependent KinasesDNA-Binding ProteinsE2F Transcription FactorsHumansMelanocytesMelanomaPhosphorylationRetinoblastoma ProteinRetinoblastoma-Binding Protein 1Signal TransductionTranscription Factor DP1Transcription FactorsConceptsPocket proteinsExternal growth factorsNormal melanocytesE2F activityTarget genesRb/E2F pathwayE2F transcription factorsCell surface receptor stimulationMelanoma cellsCell-autonomous growthTumor suppressor proteinClass of enzymesCyclin-dependent kinasesInactivation of pRbConstitutive high expressionGrowth factorCell cycle progressionSurface receptor stimulationMetastatic melanoma cellsRetinoblastoma familySuppressive complexE2F pathwayPositive regulatorTranscription factorsMouse melanocytes
1997
Recognition of activated CSF-1 receptor in breast carcinomas by a tyrosine 723 phosphospecific antibody
Flick M, Sapi E, Perrotta P, Maher M, Halaban R, Carter D, Kacinski B. Recognition of activated CSF-1 receptor in breast carcinomas by a tyrosine 723 phosphospecific antibody. Oncogene 1997, 14: 2553-2561. PMID: 9191055, DOI: 10.1038/sj.onc.1201092.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnimalsAntibodiesAntibody SpecificityBreast NeoplasmsCarcinoma in SituCells, CulturedCross ReactionsEpitopesFibroblastsGenes, fmsHumansImmunohistochemistryMacrophagesMiceMice, Inbred BALB CPhosphopeptidesPhosphorylationPhosphotyrosineProto-Oncogene MasReceptor, Macrophage Colony-Stimulating FactorTumor Cells, CulturedConceptsCSF-1RMultiple signal transduction pathwaysC-fms proto-oncogenePhosphorylation state-specific antibodiesSignal transduction pathwaysCSF-1 receptorAnchorage-independent growthImmunoblots of lysatesActivation/phosphorylationEffector proteinsVivo phosphorylationCytoplasmic domainDifferentiation of macrophagesPhosphospecific antibodiesTransduction pathwaysCellular phenotypesInvasive human breast tumoursSpecific phosphopeptidesC-fms oncogeneCSF-1Proto-oncogeneHuman breast carcinomaFirst direct evidenceNormal proliferationFactor receptor
1996
UV-induced ubiquitination of RNA polymerase II: a novel modification deficient in Cockayne syndrome cells.
Bregman D, Halaban R, van Gool A, Henning K, Friedberg E, Warren S. UV-induced ubiquitination of RNA polymerase II: a novel modification deficient in Cockayne syndrome cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 1996, 93: 11586-11590. PMID: 8876179, PMCID: PMC38101, DOI: 10.1073/pnas.93.21.11586.Peer-Reviewed Original Research
1995
Identification of p90RSK as the probable CREB-Ser133 kinase in human melanocytes.
Böhm M, Moellmann G, Cheng E, Alvarez-Franco M, Wagner S, Sassone-Corsi P, Halaban R. Identification of p90RSK as the probable CREB-Ser133 kinase in human melanocytes. Molecular Cancer Research 1995, 6: 291-302. PMID: 7540859.Peer-Reviewed Original ResearchMeSH KeywordsCell CountCell DivisionCells, CulturedCyclic AMPCyclic AMP Response Element-Binding ProteinDrug SynergismEndothelinsFibroblast Growth Factor 2Growth SubstancesHematopoietic Cell Growth FactorsHepatocyte Growth FactorHumansInfant, NewbornMelanocytesPhosphorylationProtein Serine-Threonine KinasesRecombinant Fusion ProteinsRibosomal Protein S6 KinasesSerineStem Cell FactorTime FactorsTranscription FactorsConceptsSynergistic growth factorsMast/stem cell growth factorHuman melanocytesGrowth factorHepatocyte growth factor/scatter factorActivation of p90RSKGrowth factor/scatter factorStem cell growth factorCAMP-responsive element binding proteinKID domainElement-binding proteinNormal human melanocytesTranscription factor 1Peptide growth factorsSer133 phosphorylationTranscriptional activationCell divisionPhosphorylated stateTranscription factorsInduces phosphorylationRegulatory proteinsSignal transducerFibroblast growth factorBasic fibroblast growth factorBinding protein
1993
KIT ligand (mast cell growth factor) inhibits the growth of KIT-expressing melanoma cells.
Zakut R, Perlis R, Eliyahu S, Yarden Y, Givol D, Lyman S, Halaban R. KIT ligand (mast cell growth factor) inhibits the growth of KIT-expressing melanoma cells. Oncogene 1993, 8: 2221-9. PMID: 7687762.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceCell DivisionHematopoietic Cell Growth FactorsHumansMelanomaMolecular Sequence DataNeoplasm ProteinsPhosphorylationProtein-Tyrosine KinasesProto-Oncogene MasProto-Oncogene ProteinsProto-Oncogene Proteins c-kitRNA, MessengerRNA, NeoplasmStem Cell FactorTumor Cells, CulturedConceptsMast cell growth factorMelanoma cell linesNormal melanocyte developmentMelanoma cellsAberrant signal transductionMetastatic melanoma cell linesCell linesActivation of KITMelanocyte developmentSignal transductionKIT proto-oncogeneKinase activationKIT mRNAKit ligandNormal melanocytesProto-oncogeneKIT kinaseCell growth factorBiological responsesGrowth factorHuman melanomaMelanocytesCellsKIT expressionNeoplastic melanocytesmet and HGF-SF in normal melanocytes and melanoma cells.
Halaban R, Rubin J, White W. met and HGF-SF in normal melanocytes and melanoma cells. 1993, 65: 329-39. PMID: 8380740.Peer-Reviewed Original ResearchConceptsHGF-SFFactor-dependent cellsMelanoma cellsNormal human melanocytesSignal transductionMouse melanocytesTumorigenic phenotypeHuman melanocytesHuman melanoma cellsNormal melanocytesAutocrine loopMelanocytesHuman melanomaMalignant conversionMelanin contentTyrosinase activityEctopic sitesCellsSynergistic factorExpressionBFGFERK2TransductionPhosphorylationProtein
1992
Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells.
Halaban R, Rubin J, Funasaka Y, Cobb M, Boulton T, Faletto D, Rosen E, Chan A, Yoko K, White W. Met and hepatocyte growth factor/scatter factor signal transduction in normal melanocytes and melanoma cells. Oncogene 1992, 7: 2195-206. PMID: 1331934.Peer-Reviewed Original ResearchConceptsHGF/SFMast cell growth factorSignal transductionBasic fibroblast growth factorProtein kinase/extracellular signal-regulated kinaseHuman melanocytesMalignant human melanocytesExtracellular signal-regulated kinaseHepatocyte growth factor/scatter factorGrowth factor/scatter factorSignal-regulated kinaseActivation of microtubuleProto-oncogene c-metTransmembrane tyrosine kinase receptorActivation of METC-MetTyrosine kinase receptorsNormal human melanocytesGrowth factorMouse melanocytesTyrosine phosphorylationBiological roleFibroblast growth factorKinase receptorsConstitutive activityScatter factor and hepatocyte growth factor: activities, properties, and mechanism.
Bhargava M, Joseph A, Knesel J, Halaban R, Li Y, Pang S, Goldberg I, Setter E, Donovan M, Zarnegar R. Scatter factor and hepatocyte growth factor: activities, properties, and mechanism. Molecular Cancer Research 1992, 3: 11-20. PMID: 1534687.Peer-Reviewed Original ResearchConceptsHepatocyte growth factorScatter factorPartial amino acid sequence dataAmino acid sequence dataAmino acid sequenceFibroblast-derived proteinHuman smooth muscle cellsVascular endothelial cell typesEndothelial cell typesGrowth factorSignificant homologyPosttranslational modificationsSequence dataRapid phosphorylationAcid sequenceBiological activityTyrosine residuesProtein productsCohesive coloniesCommon antigenic determinantsCell typesSpecies-related differencesProteinSerum-derived proteinsHuman hepatocyte growth factor