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1、cAMP(CyclicAdenosine3',5'-monophosphate)isthefirstidentifiedsecondmessenger,whichhasafundamentalroleinthecellularresponsetomanyextracellularstimuli.ThecAMPsignalingpathwaycontrolsadiverserangeofcellularprocesses.Indeed,notonlydidcAMPprovidetheparadigmforthesecondmesseng
2、erconcept,butalsoprovidedtheparadigmforsignalingcompartmentalization.Thedifferentreceptors,chieflytheGPCRs(G-ProteinCoupledReceptors),AlphaandBeta-ADRs(AdrenergicReceptors),GrowthFactorreceptors,CRHR(CorticotropinReleasingHormoneReceptor),GcgR(GlucagonReceptor),DCC(Dele
3、tedinColorectalCarcinoma),etcareresponsibleforcAMPaccumulationincellsthatcausedifferentphysiologicaloutcomes,andchangesincAMPlevelseffectstheselectiveactivationofPKA(cAMPdependentProteinKinase-A)isoforms.ThechiefsourceofcAMPisfromATP(AdenosineTriphosphate).Inmammals,the
4、conversionofATPtocAMPismediatedbymembersoftheClass-IIIAC(AdenylylCyclase)/ADCY(AdenylateCyclase)family(E.C4.6.1.1),whichinhumanscomprisesninetrans-membraneACenzymesortmACsandonesolubleACorsAC(Ref.1&2).ThesACpredominantlyoccursinmaturespermatozoa.tmACsareregulatedbyheter
5、otrimericG-proteinsinresponsetothestimulationofvarioustypesofGPCRsandthereforeplayakeyroleinthecellularresponsetoextracellularsignals.sAC,incontrast,isinsensitivetoG-proteins.Instead,sACisdirectlyactivatedbyCa2+(CalciumIons)andthemetaboliteHCO3-(BicarbonateIons),renderi
6、ngtheenzymeanintracellularmetabolicsensor.Together,tmACsandsACregulateadiversesetofessentialbiologicalprocesses,suchasdifferentiationandgenetranscription,andthismakescAMPsignaling,animportantmediatorofintra-andextracellularsignalsinorganismsfromprokaryotestohighereukary
7、otes(Ref.2&3).Theextracellularstimulilikeneurotransmitters,hormones,inflammatorystimuli,stress,epinephrine,norepinephrine,etcactivatetheG-proteinsthroughreceptorslikeGPCRsandADR-Alpha/Beta.ThemajorG-proteinsthatregulateactivationofACsaretheGN-AlphaS(GN-AlphaSComplexLocu
8、s),GN-AlphaQ(GuanineNucleotide-BindingProtein-Alpha-Q)andGN-AlphaI(GuanineNucleotideBindingProtein-AlphaInhibi
