2015
Downregulation of the Ubiquitin Ligase RNF125 Underlies Resistance of Melanoma Cells to BRAF Inhibitors via JAK1 Deregulation
Kim H, Frederick DT, Levesque MP, Cooper ZA, Feng Y, Krepler C, Brill L, Samuels Y, Hayward NK, Perlina A, Piris A, Zhang T, Halaban R, Herlyn MM, Brown KM, Wargo JA, Dummer R, Flaherty KT, Ronai Z. Downregulation of the Ubiquitin Ligase RNF125 Underlies Resistance of Melanoma Cells to BRAF Inhibitors via JAK1 Deregulation. Cell Reports 2015, 11: 1458-1473. PMID: 26027934, PMCID: PMC4681438, DOI: 10.1016/j.celrep.2015.04.049.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCell Line, TumorChromatography, LiquidDown-RegulationDrug Resistance, NeoplasmEnzyme InhibitorsFemaleHeterograftsHumansImmunoblottingImmunohistochemistryImmunoprecipitationJanus Kinase 1Mass SpectrometryMelanomaMiceMice, NudeProto-Oncogene Proteins B-rafRNA, Small InterferingTransfectionUbiquitin-Protein LigasesConceptsBRAF inhibitorsRTK expressionReceptor tyrosine kinasesRemarkable clinical responsesBRAFi-resistant melanomasInhibition of JAK1BRAFi-resistant tumorsClinical responseCombination therapyMost tumorsBRAF mutationsTumor specimensVivo xenograftsBRAFi resistanceMelanoma cellsElevated expressionMelanomaEGFRAdaptive resistanceTumorsRNF125MITF expressionTyrosine kinaseJAK1Downregulation
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
1997
Diminished TCR signaling in cutaneous T cell lymphoma is associated with decreased activities of Zap70, Syk and membrane-associated Csk
Fargnoli M, Edelson R, Berger C, Chimenti S, Couture C, Mustelin T, Halaban R. Diminished TCR signaling in cutaneous T cell lymphoma is associated with decreased activities of Zap70, Syk and membrane-associated Csk. Leukemia 1997, 11: 1338-1346. PMID: 9264390, DOI: 10.1038/sj.leu.2400745.Peer-Reviewed Original ResearchMeSH KeywordsAdultCSK Tyrosine-Protein KinaseEnzyme ActivationEnzyme PrecursorsHumansImmunophenotypingIntracellular Signaling Peptides and ProteinsLymphoma, T-Cell, CutaneousPhosphotyrosineProtein-Tyrosine KinasesReceptors, Antigen, T-CellSignal TransductionSkin NeoplasmsSrc-Family KinasesSyk KinaseT-LymphocytesZAP-70 Protein-Tyrosine KinaseConceptsCutaneous T-cell lymphomaProtein tyrosine kinasesFunction of membersSignal transduction moleculesWeak mitogenic responseActivity of SykTCR ζ-chainCell surface receptorsTCR/CD3Membrane-bound fractionCellular proteinsTyrosyl phosphorylationT-cell lymphomaTyrosine phosphorylationTransduction moleculesLck kinaseTyrosine kinaseDistinct familiesΖ chainEffector moleculesKinaseSurface receptorsEnzymatic activityCell lymphomaNeoplastic cells
1993
White Mutants in Mice Shedding Light on Humans
Halaban R, Moellmann G. White Mutants in Mice Shedding Light on Humans. Journal Of Investigative Dermatology 1993, 100: s176-s185. DOI: 10.1038/jid.1993.73.Peer-Reviewed Original ResearchMembrane receptor tyrosine kinasesMouse mutant modelsPink-eyed dilutionDefective signal transductionReceptor kinase activityEnzyme activityC-kitDistinct enzyme activitiesIdentification of mutationsRespective enzyme activitiesPiebald phenotypeShares homologyLocus proteinSignal transductionKinase activityCatalase BMolecular geneticsTyrosine kinaseWhite mutantsMutant modelsHair melanocytesPoint mutationsTyrosinase-negative albinismNormal pigmentationProliferation of melanocytesWhite mutants in mice shedding light on humans.
Halaban R, Moellmann G. White mutants in mice shedding light on humans. Journal Of Investigative Dermatology 1993, 100: 176s-185s. PMID: 8433006, DOI: 10.1038/jid.1993.10.Peer-Reviewed Original ResearchConceptsMembrane receptor tyrosine kinasesMouse mutant modelsPink-eyed dilutionDefective signal transductionReceptor kinase activityEnzyme activityC-kitDistinct enzyme activitiesIdentification of mutationsRespective enzyme activitiesPiebald phenotypeShares homologyLocus proteinSignal transductionKinase activityCatalase BMolecular geneticsTyrosine kinaseWhite mutantsMutant modelsHair melanocytesDopachrome tautomerasePoint mutationsTyrosinase-negative albinismNormal pigmentation
1992
Growth Factors, Receptor Kinases, and Protein Tyro sine Phosphatases in Normal and Malignant Melanocytes
Halaban R, Fan B, Ahn J, Funasaka Y, Gitay-Goren H, Neufeld G. Growth Factors, Receptor Kinases, and Protein Tyro sine Phosphatases in Normal and Malignant Melanocytes. Journal Of Immunotherapy 1992, 12: 154-161. PMID: 1445804, DOI: 10.1097/00002371-199210000-00002.Peer-Reviewed Original ResearchConceptsMast cell growth factorReceptor tyrosine kinasesFibroblast growth factorTyrosine kinaseTyrosyl-phosphorylated proteinsExpression of pigmentationTransmembrane receptor tyrosine kinaseHepatocyte growth factorGrowth factorGrowth factor/receptor systemsHuman melanocyte proliferationBasic FGFMelanoma cellsProtein tyrosineReceptor kinasePigment cellsBasic fibroblast growth factorFGF receptorsKinaseHuman melanoma cellsNormal melanocytesKIT kinaseMalignant phenotypeMelanocyte proliferationCell growth factor
1991
Growth factors and tyrosine protein kinases in normal and malignant melanocytes
Halaban R. Growth factors and tyrosine protein kinases in normal and malignant melanocytes. Cancer And Metastasis Reviews 1991, 10: 129-140. PMID: 1873853, DOI: 10.1007/bf00049410.Peer-Reviewed Original ResearchConceptsMast cell growth factorTyrosine kinase activityKinase activityBasic fibroblast growth factorNormal melanocyte proliferationTyrosine kinaseExogenous peptide growth factorsHepatocyte growth factorGrowth factorTyrosine protein kinaseAberrant gene expressionMelanocyte proliferationTransmembrane tyrosine kinaseReceptor tyrosine kinasesEnvironmental growth factorsNormal human melanocytesPeptide growth factorsMouse melanocytesProtein kinaseGrowth factor receptorUncontrolled growthC-kitGene expressionConstitutive expressionFibroblast growth factorProliferation and malignant transformation of melanocytes.
Halaban R, Moellmann G. Proliferation and malignant transformation of melanocytes. Critical Reviews™ In Oncogenesis 1991, 2: 247-58. PMID: 1958709.Peer-Reviewed Original ResearchConceptsActive receptor tyrosine kinasesTissue-specific genesReceptor tyrosine kinasesSignal transmission pathwaysGrowth factor receptorLow molecular weight inhibitorsUnregulated expressionCertain chromosomesTyrosine kinaseGenesNormal melanocytesMalignant transformationMouse fibroblastsFactor receptorDrug designWeight inhibitorsKaryotypic changesKinaseMelanoma-prone familiesGrowth factorOncogeneHuman melanomaMelanocytesMelanoma growthTransmission pathways