2020
FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho
Suzuki Y, Kuzina E, An SJ, Tome F, Mohanty J, Li W, Lee S, Liu Y, Lax I, Schlessinger J. FGF23 contains two distinct high-affinity binding sites enabling bivalent interactions with α-Klotho. Proceedings Of The National Academy Of Sciences Of The United States Of America 2020, 117: 31800-31807. PMID: 33257569, PMCID: PMC7749347, DOI: 10.1073/pnas.2018554117.Peer-Reviewed Original ResearchMeSH KeywordsBinding SitesCalcinosisCell MembraneFibroblast Growth Factor-23Fibroblast Growth FactorsGlucuronidaseHEK293 CellsHumansHyperostosis, Cortical, CongenitalHyperphosphatemiaImmunoglobulin Fc FragmentsKlotho ProteinsMutationOsteomalaciaProtein BindingProtein DomainsProtein MultimerizationRecombinant Fusion ProteinsRickets, HypophosphatemicConceptsFGF receptorsTotal internal reflection fluorescence microscopyChimeric receptor moleculesReflection fluorescence microscopyBinding sitesDisulfide bridge formationCritical metabolic processesMAPK responseCytoplasmic domainGrowth factor familyTerminal tailFactor familyKinase activationSimilar binding affinitiesExtracellular domainFGFR1 activationTandem repeatsMetabolic processesDisulfide bridgesCell surfaceDistinct ligandsCell membraneFluorescence microscopyDistinct high-affinity binding sitesPhosphate homeostasis
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
2009
The Selectivity of Receptor Tyrosine Kinase Signaling Is Controlled by a Secondary SH2 Domain Binding Site
Bae J, Lew E, Yuzawa S, Tomé F, Lax I, Schlessinger J. The Selectivity of Receptor Tyrosine Kinase Signaling Is Controlled by a Secondary SH2 Domain Binding Site. Journal Of End-to-End-testing 2009, 138: 514-524. DOI: 10.1016/s9999-9994(09)20438-7.Peer-Reviewed Original ResearchSH2 domainSH2 domain-mediated interactionsReceptor tyrosine kinase signalingPhosphorylation-independent mannerReceptor phosphorylation sitesDomain-mediated interactionsDomain Binding SiteSpecific cellular processesTyrosine kinase signalingParticular sequence motifsReceptor tyrosine kinasesBinding sitesTyrosine kinase domainPhosphorylation sitesCellular processesSequence motifsKinase signalingKinase domainPhospholipase CγTyrosine kinaseSecondary binding siteCultured cellsDomain selectivityRegulation of selectivityIndependent mannerThe Selectivity of Receptor Tyrosine Kinase Signaling Is Controlled by a Secondary SH2 Domain Binding Site
Bae JH, Lew ED, Yuzawa S, Tomé F, Lax I, Schlessinger J. The Selectivity of Receptor Tyrosine Kinase Signaling Is Controlled by a Secondary SH2 Domain Binding Site. Cell 2009, 138: 514-524. PMID: 19665973, PMCID: PMC4764080, DOI: 10.1016/j.cell.2009.05.028.Peer-Reviewed Original ResearchConceptsSH2 domainSH2 domain-mediated interactionsReceptor tyrosine kinase signalingPhosphorylation-independent mannerReceptor phosphorylation sitesDomain-mediated interactionsDomain Binding SiteSpecific cellular processesTyrosine kinase signalingParticular sequence motifsReceptor tyrosine kinasesBinding sitesTyrosine kinase domainPhosphorylation sitesCellular processesSequence motifsPhospholipase CgammaKinase signalingKinase domainTyrosine kinaseSecondary binding siteCultured cellsDomain selectivityRegulation of selectivityIndependent manner