2023
Heparin is essential for optimal cell signaling by FGF21 and for regulation of βKlotho cellular stability
An S, Mohanty J, Tome F, Suzuki Y, Lax I, Schlessinger J. Heparin is essential for optimal cell signaling by FGF21 and for regulation of βKlotho cellular stability. Proceedings Of The National Academy Of Sciences Of The United States Of America 2023, 120: e2219128120. PMID: 36745784, PMCID: PMC9962926, DOI: 10.1073/pnas.2219128120.Peer-Reviewed Original ResearchMeSH KeywordsAnimalsCHO CellsCricetinaeCricetulusFibroblast Growth Factor 1Fibroblast Growth FactorsHeparan Sulfate ProteoglycansHeparinKlotho ProteinsSignal TransductionConceptsHeparan sulfate proteoglycanCellular stabilityCell membraneSingle-molecule fluorescenceProtein kinase responsesChinese hamster ovary cellsFGF moleculesHamster ovary cellsFactor bindsReceptor assemblyReceptor dimerizationGrowth factor bindsHigh-affinity bindingFGF1 stimulationKinase responseCHO cellsOvary cellsSulfate proteoglycanIntracellular CaKlotho proteinFGFR1cPotential roleRegulationΒKlothoCells
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