Sphingosine-1-phosphate(S1P)isanexampleoflipidmessengerswithbothintracellularandextracellularfunctions.IntracellularlyS1Pregulatesproliferationandsurvival;extracellularlyS1PisaligandforEDG1(alsoknownasS1P1).Activationofsphingosinekinase(SPHK),theenzymethatcatalyzesthephosphorylationofsphingosine,increasescellularlevelsofS1P.InhibitorsofSPHKblockformationofS1Pandinhibitcellularproliferationinducedbyavarietyoffactors,includingasanexampleplatelet-derivedgrowthfactor(PDGF)andPMA.InastudyusingendothelialcellsitwasdemonstratedthatS1Pinducesactivationofalpha-vandB3integrinsviaRhoA.S1PalsoactivatesAktviaGiandPI3K.TheactivatedAktphosphorlyatestheEdg1receptoronthreonine236leADIngtotheactivationofRac1andsubsequentsignalsleadingtoactinassembly,chemotaxisandlamellipodiaformation.Edg1stimulationalsoleadstotheactivationoftheERKsignalingcascaderesultinginanti-apoptoticreversal,proliferationandcellsurvival.

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REFERENCES:BaudhuinLM,CristinaKL,LuJ,XuY.Aktactivationinducedbylysophosphatidicacidandsphingosine-1-phosphaterequiresbothmitogen-activatedproteinkinasekinaseandp38mitogen-activatedproteinkinaseandiscell-linespecific.MolPharmacol.2002Sep;62(3):660-71.HlaT,LeeMJ,AncellinN,PaikJH,KlukMJ.Lysophospholipids--receptorrevelations.Science.2001Nov30;294(5548):1875-8.Review.JohnsonKR,BeckerKP,FacchinettiMM,HannunYA,ObeidLM.PKC-dependentactivationofsphingosinekinase1andtranslocationtotheplasmamembrane.Extracellularreleaseofsphingosine-1-phosphateinducedbyphorbol12-myristate13-acetate(PMA).JBiolChem.2002Sep20;277(38):35257-62.KarlinerJS,HonboN,SummersK,GrayMO,GoetzlEJ.Thelysophospholipidssphingosine-1-phosphateandlysophosphatidicacidenhancesurvivalduringhypoxiainneonatalratcardiacmyocytes.JMolCellCardiol.2001Sep;33(9):1713-7.KarlinerJS.Lysophospholipidsandthecardiovascularsystem.BiochimBiophysActa.2002May23;1582(1-3):216-21.Review.LacanaE,MaceykaM,MilstienS,SpiegelS.CloningandcharacterizationofaproteinkinaseAanchoringprotein(AKAP)-relatedproteinthatinteractswithandregulatessphingosinekinase1activity.JBiolChem.2002Sep6;277(36):32947-53.PanettiTS.Differentialeffectsofsphingosine1-phosphateandlysophosphatidicacidonendothelialcells.BiochimBiophysActa.2002May23;1582(1-3):190-6.Review.ParrillAL,WangD,BautistaDL,VanBrocklynJR,LorinczZ,FischerDJ,BakerDL,LiliomK,SpiegelS,TigyiG.IdentificationofEdg1receptorresiduesthatrecognizesphingosine1-phosphate.JBiolChem.2000Dec15;275(50):39379-84.ReppH,BirringerJ,KoschinskiA,DreyerF.ActivationofaCa2+-dependentK+currentinmousefibroblastsbysphingosine-1-phosphateinvolvestheproteintyrosinekinasec-Src.NaunynSchmiedebergsArchPharmacol.2001Mar;363(3):295-301.RosenfeldtHM,HobsonJP,MaceykaM,OliveraA,NavaVE,MilstienS,SpiegelS.EDG-1linksthePDGFreceptortoSrcandfocaladhesionkinaseactivationleadingtolamellipodiaformationandcellmigration.FASEBJ.2001Dec;15(14):2649-59.RyuY,TakuwaN,SugimotoN,SakuradaS,UsuiS,OkamotoH,MatsuiO,TakuwaY.Sphingosine-1-phosphate,aplatelet-derivedlysophospholipidmediator,negativelyregulatescellularRacactivityandcellmigrationinvascularsmoothmusclecells.CircRes.2002Feb22;90(3):325-32.TakuwaY,TakuwaN,SugimotoN.TheEdgfamilyGprotein-coupledreceptorsforlysophospholipids:theirsignalingpropertiesandBIOLOGicalactivities.JBiochem(Tokyo).2002Jun;131(6):767-71.Review.

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