Cataloguenumber
CYT-020
Synonyms
Introduction
Description
Source
PhysicalAppearance
Formulation
Solubility
StABIlity
Purity
Aminoacidsequence
BiologicalActivity
ThebiologicalactivityofFGF-23wasmeasuredinacellproliferationassayusingNIH/3T3mouseembryonicfibroblasts.TheED50forthiseffectistypically0.05-0.5µg/mlinthepresenceof5µg/mlofRecombinantMouseKlothoand10µg/mlofHPR.
References
Title:Leptinstimulatesfibroblastgrowthfactor23expressioninboneandsuppressesrenal1?,25-dihydroxyvitaminD3synthesisinleptin-deficientob/obMicePublication:Journalofboneandmineralresearch25.8(2010):1711-1723.Link:http://onlinelibrary.wiley.com/doi/10.1002/jbmr.65/full
SafetyDataSheet
SDS
Usage
Background
Beforeitwasdiscoveredin2000,therewasahypothesisthatasimilartypeofproteinexistedthatperformedmanyofthefunctionsweseeinFGF23.Thiswasoriginallyreferredtoasphosphatonin.Variouseffectsweredescribedandnotedbyresearchersincludinginhibitionofproductionandinhibitionofsecretionofparathyroidhormone.DerivedfromtheboneFibroblastGrowthFactor23isaphosphaturichormone.Itincreasesphosphateexcretionwhenactingonthekidneyandalsosuppressesthebiosynthesisof1,25(OH)2D3.
MechanismDespitevariousresearchstudiesintothetopic,manyofthemechanismsfortheregulationsofFGF23productionremainamysterytothescientificcommunity.WhileweknowthatmutationsinPHEX,ENPP1andDMP1resultintheincreasedexpressionofFGF23,itisunclearwhythisoccurs.Thisalsomeansthatcurrently,itisnotpossIBLetoregulatetheproductionofFGF23either.WealsodonotknowhowsignalsfromFGF23regulatevitaminDmetabolism.However,understandingthesetypesofmechanismscouldofferinformationneededtoprovidebettertreatmentforderangedboneandmineralmetabolism.
InteractionsMolecularinteractionsinvolvingFGF-23,vitaminDandklothodoprovidethesolutionneededtoregulatephosphatelevelswithinthebody.FurThermore,aninteractionbetweenVitaminDandFGF3canhaveanimpactonrenalphosphatebalance.Aswellasthis,wheninthepresenceofklotho,FGF3doesactuallyincreasebioactivityandbeginstochangesystemicphosphatehomeostasis.
FunctionBasedonresearchitseemsthatthemainfunctionforFGF23istheregulationofphosphateconcentrationinplasma.Itseemstobesecretedfromtheosteocytesduetoelevatedlevels.Whenactinguponthekidneys,thehormonereducestheexpressionofNPT2.Thisisasodium-phosphatecotransporterfoundintheproximaltube.Assuch,itappearsasthoughFGF23isabletoreducethereabsorption,allthewhilemaxingtheexcretionofphosphate.Ithasalsobeensuggestedthatthehormoneisabletosuppress1-alpha-hydroxylase.Ifthisisthecase,itcanlimititspotentialtoactivatevitaminDandthusimpairtheabilityforcalciumabsorption.
StructureFGF243islocatedonthechromosome12.Itiscomposedofthreeexons.ThecrystalstructureofFGF23iscompletelydifferentfromthecommonconformationtypicallyadoptedbyparacrine-actingFGFs.Instead,thereisaconformationoftheHPRregionbetweenbetastrands10and12.Aswellasthis,thereisacleftbetweentheotherHPR-bindingregion,thebeta1-beta12loopandthisone.ThiscomesbeforeadirectinteractionbetweenHPRsulfateandFGF23sbackboneatoms.Duetothis,endocrinefunctionisbenefittedandHPR-bindingaffinityisreducedforthelipangs.Certainmutationsthatcausetheproteintobecompletelyresistanttoproteolyticcleavagedoestriggerasurgeinactivityoftheproteinandtherenalphosphatelosstypicallyfoundincertainhumandiseasesincludinghypophosphatemicrickets.StudieshavealsorevealedthatFGF23isoverproducedincertaintumorsincludingphosphaturicmesenchymaltumors.Furthermoreareducedlevelofactivityforthisproteinisbelievedtoleadtohigherphosphatelevelsandfamilialtumorcalcinosisclinicalsyndrome.