2014
Structure, domain organization, and different conformational states of stem cell factor-induced intact KIT dimers
Opatowsky Y, Lax I, Tomé F, Bleichert F, Unger VM, Schlessinger J. Structure, domain organization, and different conformational states of stem cell factor-induced intact KIT dimers. Proceedings Of The National Academy Of Sciences Of The United States Of America 2014, 111: 1772-1777. PMID: 24449920, PMCID: PMC3918759, DOI: 10.1073/pnas.1323254111.Peer-Reviewed Original ResearchConceptsExtracellular regionConformational statesIg-like domainsReceptor tyrosine kinasesDifferent conformational statesTrans autophosphorylationTyrosine kinase domainMembrane-proximal Ig-like domainsTrans phosphorylationAutophosphorylation sitesDomain organizationKinase domainCytoplasmic regionHomotypic interactionsKinase activityReceptor dimersDimeric receptorTyrosine kinaseAsymmetric arrangementMolecular interactionsPrevalent conformationsCrystal structureAutophosphorylationDimersKinase
2013
RAC1P29S is a spontaneously activating cancer-associated GTPase
Davis MJ, Ha BH, Holman EC, Halaban R, Schlessinger J, Boggon TJ. RAC1P29S is a spontaneously activating cancer-associated GTPase. Proceedings Of The National Academy Of Sciences Of The United States Of America 2013, 110: 912-917. PMID: 23284172, PMCID: PMC3549122, DOI: 10.1073/pnas.1220895110.Peer-Reviewed Original ResearchAmino Acid SubstitutionAnimalsCell Surface ExtensionsChlorocebus aethiopsCOS CellsCrystallography, X-RayEnzyme ActivationGenetic Association StudiesGuanosine TriphosphateHumansHydrolysisKineticsMelanomaMiceMicroscopy, FluorescenceModels, MolecularMutation, MissenseNIH 3T3 CellsOncogenesRac1 GTP-Binding ProteinRecombinant Fusion ProteinsSignal TransductionStatic Electricity
2007
Structural basis for reduced FGFR2 activity in LADD syndrome: Implications for FGFR autoinhibition and activation
Lew ED, Bae JH, Rohmann E, Wollnik B, Schlessinger J. Structural basis for reduced FGFR2 activity in LADD syndrome: Implications for FGFR autoinhibition and activation. Proceedings Of The National Academy Of Sciences Of The United States Of America 2007, 104: 19802-19807. PMID: 18056630, PMCID: PMC2148379, DOI: 10.1073/pnas.0709905104.Peer-Reviewed Original ResearchMeSH KeywordsAbnormalities, MultipleAdenosine TriphosphateAlanineCrystallography, X-RayHumansModels, MolecularMutationPhosphorylationProtein BindingProtein Structure, TertiaryReceptor, Fibroblast Growth Factor, Type 1Receptor, Fibroblast Growth Factor, Type 2Structural Homology, ProteinSubstrate SpecificitySyndromeConceptsFibroblast growth factor receptor 2Tyrosine kinase activityKinase activityStatic crystallographic snapshotsKinase hinge regionSevere skeletal disorderTyrosine kinase domainAutophosphorylation kineticsFGFR2 kinaseFGFR1 kinaseKinase domainKey residuesStructural basisMutation altersFGFR2 activityConformational dynamicsCrystallographic snapshotsStringent modeCatalytic pocketFGF receptorsFunction mutationsKinaseMultiple gainsMissense mutationsAutoinhibitionStructural Basis for Activation of the Receptor Tyrosine Kinase KIT by Stem Cell Factor
Yuzawa S, Opatowsky Y, Zhang Z, Mandiyan V, Lax I, Schlessinger J. Structural Basis for Activation of the Receptor Tyrosine Kinase KIT by Stem Cell Factor. Cell 2007, 130: 323-334. PMID: 17662946, DOI: 10.1016/j.cell.2007.05.055.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceBinding SitesCrystallography, X-RayDimerizationDiseaseEnzyme ActivationHumansLigandsModels, MolecularMolecular Sequence DataMutationProtein BindingProtein Structure, SecondaryProtein Structure, TertiaryProto-Oncogene Proteins c-kitStem Cell FactorStructure-Activity RelationshipConceptsStem cell factorReceptor dimerizationLigand-induced receptor dimerizationCell factorMultiple cellular responsesTyrosine kinase activationReceptor tyrosine kinase KITKIT dimerizationTyrosine kinase KITDomain D4Structural basisCritical residuesKinase activationSCF stimulationCellular responsesConformational changesOncogenic mutationsCultured cellsAmino acidsPoint mutationsKIT activationEntire ectodomainKinase KITKey hallmarksSole role