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1、REVIEWSSPHINGOSINE-1-PHOSPHATE:ANENIGMATICSIGNALLINGLIPIDSarahSpiegel*andSheldonMilstien‡Theevolutionarilyconservedactionsofthesphingolipidmetabolite,sphingosine-1-phosphate(S1P),inyeast,plantsandmammalshaveshownthatithasimportantfunctions.Inhighereukaryotes,S1PistheligandforafamilyoffiveG-pro
2、tein-coupledreceptors.TheseS1Preceptorsaredifferentiallyexpressed,coupledtovariousGproteins,andregulateangiogenesis,vascularmaturation,cardiacdevelopmentandimmunity,andareimportantfordirectedcellmovement.Sphingosine-1-phosphate(S1P)isderivedfrom(SphK;BOX1),whichcatalysestheATP-dependentsphingo
3、sine—thebackboneofmostsphingolipidsphosphorylationofsphingosine,isstimulatedbymany—anditisnowemergingasavitallipidmediator.agonists,whichindicatesthatthisisacentralregulatingSphingosinewasnamedin1884aftertheGreekenzymeofS1P.ThedegradationofS1Pismediatedbymythologicalcreature,theSphinx,becauseo
4、fitsenig-twodifferentpathways:oneisthereversibledephos-maticnature1.MorethanacenturylaterwearejustphorylationbacktosphingosinebyspecificS1PbeginningtounraveltheriddleofS1P.S1Pwasorigi-phosphatases(BOX1);thesecondistheirreversiblenallyconsideredtobeformedmerelyasaninterme-degradationbyapyridoxa
5、lphosphate-dependentS1Pdiateinthedetoxificationofsphingosine,byitslyase(Spl)(BOX1)tohexadecenalandphospho-phosphorylationandsubsequentdegradation2(FIG.1),ethanolamine,whicharesubsequentlyreusedforthebutsincethediscoverythatS1Pregulatescellbiosynthesisofphosphatidylethanolamine(FIG.1).growth3,4
6、andsuppressesprogrammedcelldeath5,therehasbeenanexplosionofimportantphysiologi-Sphingosinekinases.SphKsareadistinctandnewlycalandpathophysiologicalprocessesthatarereporteddiscoveredclassoflipidkinasethathavefiveconservedtoberegulatedbyS1Pinhigherorganisms.S1Panddomainsandareevolutionarilyconse
7、rved.Theyareitshomologousphosphorylatedlong-chainsphingoidexpressedinhumans,mice,yeastandplants,withbaseshavebeendetectedinplants,worms,flies,slimehomologuesinwormsandflies.Twomammalianmouldandyeast,andtheyalsoregulateimportantisozymes,
