2016
RASopathy Gene Mutations in Melanoma
Halaban R, Krauthammer M. RASopathy Gene Mutations in Melanoma. Journal Of Investigative Dermatology 2016, 136: 1755-1759. PMID: 27236105, PMCID: PMC4992636, DOI: 10.1016/j.jid.2016.05.095.Peer-Reviewed Original ResearchConceptsRASopathy mutationsRAS/mitogen-activated protein kinaseRAS/mitogen-activated protein kinase (MAPK) pathwayMitogen-activated protein kinase pathwayMitogen-activated protein kinaseProtein kinase pathwayAmino acid substitutionsNext-generation sequencingProtein kinasePathway genesKinase pathwaySequencing dataDriver genesAcid substitutionsGenomic abnormalitiesMutationsLegius syndromeGenesAbundant mutationsGermline mutationsGene mutationsPathwaySignificant overlapKinaseMelanomagenesisAMPK promotes tolerance to Ras pathway inhibition by activating autophagy
Sanduja S, Feng Y, Mathis RA, Sokol ES, Reinhardt F, Halaban R, Gupta PB. AMPK promotes tolerance to Ras pathway inhibition by activating autophagy. Oncogene 2016, 35: 5295-5303. PMID: 27041569, PMCID: PMC6086350, DOI: 10.1038/onc.2016.70.Peer-Reviewed Original ResearchConceptsCellular energy sensor AMPEnergy sensor AMPPathway inhibitorTargeted inhibitorsRas-Raf pathwayDrug-tolerant cellsPathway inhibitionOncogenic RasProtein kinaseRaf signalingRas pathway inhibitionReduced growthAMPKAutophagyPathway mutationsCancer cellsResistant cellsKey mechanismPathwayInhibitorsCellsToleranceKinaseSignalingInhibition
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
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
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
Proliferation 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