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
2010
Asymmetric receptor contact is required for tyrosine autophosphorylation of fibroblast growth factor receptor in living cells
Bae JH, Boggon TJ, Tomé F, Mandiyan V, Lax I, Schlessinger J. Asymmetric receptor contact is required for tyrosine autophosphorylation of fibroblast growth factor receptor in living cells. Proceedings Of The National Academy Of Sciences Of The United States Of America 2010, 107: 2866-2871. PMID: 20133753, PMCID: PMC2840318, DOI: 10.1073/pnas.0914157107.Peer-Reviewed Original ResearchConceptsReceptor tyrosine kinasesTyrosine autophosphorylationKinase moleculesTyrosine kinaseFGFR1 kinase domainSpecific docking sitesAsymmetric dimer formationFibroblast growth factor receptorActivation of intracellularKinase domainOncogenic activating mutationsGrowth factor receptorMolecular basisDocking siteKinase activityBiochemical experimentsActive enzymeN-lobeC-lobeFGF receptorsFunction mutationsAutophosphorylationTransphosphorylationLiving cellsFactor receptor
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 mutationsAutoinhibition
1991
A Dominant Negative Mutation Suppresses the Function of Normal Epidermal Growth Factor Receptors by Heterodimerization
Kashles O, Yarden Y, Fischer R, Ullrich A, Schlessinger J. A Dominant Negative Mutation Suppresses the Function of Normal Epidermal Growth Factor Receptors by Heterodimerization. Molecular And Cellular Biology 1991, 11: 1454-1463. DOI: 10.1128/mcb.11.3.1454-1463.1991.Peer-Reviewed Original ResearchDominant negative mutationWild-type receptorEpidermal growth factorNegative mutationMutant receptorsWild-type EGF receptorEGF receptorResponse to EGFInactive deletion mutantsCovalent cross-linking experimentsLiving cellsWild-typeEpidermal growth factor receptorRate of receptor endocytosisCross-linking experimentsDeletion mutantsTyrosine autophosphorylationCytoplasmic domainCells expressing wild-type receptorsReceptor endocytosisMurine embryogenesisKinase activityHigh-affinity binding sitesReceptor dimerizationNormal receptorsEpidermal Growth Factor (EGF) Stimulates Association and Kinase Activity of Raf-1 with the EGF Receptor
App H, Hazan R, Zilberstein A, Ullrich A, Schlessinger J, Rapp U. Epidermal Growth Factor (EGF) Stimulates Association and Kinase Activity of Raf-1 with the EGF Receptor. Molecular And Cellular Biology 1991, 11: 913-919. DOI: 10.1128/mcb.11.2.913-919.1991.Peer-Reviewed Original ResearchRaf-1Raf-1 kinaseEpidermal growth factorPhosphorylation of c-Raf-1Kinase activityKinase activity of Raf-1Activation of Raf-1Phosphorylation of Raf-1Sodium dodecyl sulfate gelsRaf-1 activationImmunocomplex kinase assayEGF signal transductionC-Raf-1Dodecyl sulfate gelsTyrosine kinase activityTyrosine phosphorylationSerine residuesHistone H1Kinase assaySignal transductionDownstream effectorsStimulated associationEGF receptorKinaseGrowth factor