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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