2019
Structures of ligand-occupied β-Klotho complexes reveal a molecular mechanism underlying endocrine FGF specificity and activity
Kuzina ES, Ung PM, Mohanty J, Tome F, Choi J, Pardon E, Steyaert J, Lax I, Schlessinger A, Schlessinger J, Lee S. Structures of ligand-occupied β-Klotho complexes reveal a molecular mechanism underlying endocrine FGF specificity and activity. Proceedings Of The National Academy Of Sciences Of The United States Of America 2019, 116: 7819-7824. PMID: 30944224, PMCID: PMC6475419, DOI: 10.1073/pnas.1822055116.Peer-Reviewed Original ResearchConceptsFGF receptorsPleiotropic cellular responsesFibroblast growth factor (FGF) familyPrimary high-affinity receptorsKlotho proteinChimeric mutantsGrowth factor familyCatalytic subunitFGFR functionRegulatory interactionsTerminal tailPleiotropic cellular effectsFactor familyP motifS motifExtracellular domainMolecular mechanismsIntracellular signalingCellular responsesSame binding siteCellular effectsGeneral mechanismEndocrine FGFsBinary complexBinding sites
2015
Augmentor α and β (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: Hierarchy and specificity of ligand–receptor interactions
Reshetnyak AV, Murray PB, Shi X, Mo ES, Mohanty J, Tome F, Bai H, Gunel M, Lax I, Schlessinger J. Augmentor α and β (FAM150) are ligands of the receptor tyrosine kinases ALK and LTK: Hierarchy and specificity of ligand–receptor interactions. Proceedings Of The National Academy Of Sciences Of The United States Of America 2015, 112: 15862-15867. PMID: 26630010, PMCID: PMC4702955, DOI: 10.1073/pnas.1520099112.Peer-Reviewed Original ResearchMeSH KeywordsAmino Acid SequenceAnaplastic Lymphoma KinaseAnimalsCell LineCell Line, TumorCell ProliferationCytokinesDoxycyclineEnzyme ActivationHEK293 CellsHeparinHumansImmunoblottingLigandsMiceMolecular Sequence DataNIH 3T3 CellsProtein BindingReceptor Protein-Tyrosine KinasesSequence Homology, Amino AcidConceptsLeukocyte tyrosine kinaseReceptor tyrosine kinasesTyrosine kinaseIL-3-independent growthCritical cellular functionsBa/F3 cellsCell surface receptorsAnaplastic lymphoma kinaseLigand-receptor interactionsCellular functionsLigand bindingF3 cellsReceptor tyrosineProtein ligandsNIH/3T3 cellsKinaseSurface receptorsIndependent growthSubnanomolar potencyCellsDisease statesHigh affinityLymphoma kinaseFAM150ANovel cytokine
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