Type:Protein
SpeciesReactivity:H
B=Bovine;Ca=Cat;Ch=Chicken;D=Dog;EQ=Equine;GP=GuineaPig;H=Human;M=Mouse;P=Porcine;Pr=Primate;R=Rat;Rb=Rabbit;Y=Yeast;Xe=Xenopus;Ze=Zebrafish;;;;NA-NotApplicable;STP=Step-TactinProteins;All
TheFGFsareafamilyofmorethan20small(~17–26kDa)secretedpeptides.TheinitialcharacterizationoftheseproteinsfocusedontheirABIlitytostimulatefibroblastproliferation.ThismitogenicactivitywasmediatedthroughFGFreceptors(FGFRs)1,2,or3.Afourthcloselyrelatedtyrosinekinasereceptor(FGFR4)wasabletobindtheFGFsbutdidnotleadtoamitogenicresponse.FGFsmodulatecellularactivityviaatleast5distinctsubfamiliesofhigh-affinityFGFreceptors(FGFRs):FGFR-1,-2,-3,and-4,allwithintrinsictyrosinekinaseactivityand,exceptforFGFR-4,multiplespliceisoforms,andFGFR-5,whichlacksanintracellularkinasedomain.ThereisgrowingevidencethatFGFRscanbeimportantforregulationofglucoseandlipidhomeostasis.TheoverexpressionofadominantnegativeformofFGFR-1inβcellsleadstodiabetesinmice,whichthusimpliesthatproperFGFsignalingisrequiredfornormalβcellfunctionandglycemiamaintenance.FGFR-2appearstobeakeymoleculeduringpancreaticdevelopment.Moreover,FGFR-4hasbeenimplicatedincholesterolmetabolismandbileacidsynthesis.FGF-19,hasbeenshowntocauseresistancetodiet-inducedobesityandinsulindesensitizationandtoimproveinsulin,glucose,andlipidprofilesindiabeticrodents.Sincetheseeffects,atleastinpart,aremediatedthroughtheobservedchangesinmetabolicrates,FGF-19canbeconsideredasaregulatorofenergyexpenditure.FGF-21ispreferentiallyexpressedinliver,butanexactknowledgeofFGF-21bioactivityanditsmodeofactionhavebeenlackingtodate.FGF-21isapotentactivatorofglucoseuptakeonADIpocytes,protectsanimalsfromdiet-inducedobesitywhenoverexpressedintransgenicmice,andlowersbloodglucoseandtriglyceridelevelswhentherapeuticallyadmiNISTeredtodiabeticrodents.
Image:FGF-19proteinstructureandsequence
References:
1.Molecularinsightsintotheklotho-dependent,endocrinemodeofactionoffibroblastgrowthfactor19subfamilymembers. MolCellBiol2007May;27(9):3417-28
2.Biliarysecretionandexcretioninhealthanddisease:currentconcepts. AnnHepatol2007Jan-Mar;6(1):15-27
3.Circulatingintestinalfibroblastgrowthfactor19hasapronounceddiurnalvariationandmodulateshepaticbileacidsynthesisinman. JInternMed2006Dec;260(6):530-6
4.Effectsoffibroblastgrowthfactors19and20oncellmultiplicationandlocomotioninahumanembryonalcarcinomacellline(Tera-2)invitro. AnticancerRes2006Sep-Oct;26(5A):3307-10
5.AroleforFXRandhumanFGF-19intherepressionofparaoxonase-1geneexpressionbybileacids. JLipidRes2006Feb;47(2):384-92
6.ExpressionofFibroblastgrowthfactor19(Fgf19)duringchickenembryogenesisandeyedevelopment,comparedwithFgf15expressioninthemouse.GeneExprPatterns2004Oct;4(6):687-93
