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1、cAMP(CyclicAdenosine3',5'-monophosphate)isthefirstidentifiedsecondmessenger,whichhasafundamentalroleinthecellularresponsetomanyextracellularstimuli.ThecAMPsignalingpathwaycontrolsadiverserangeofcellularprocesses.Indeed,notonlydidcAMPprovidetheparadigmforthesecondmessengerconcept,butalsoprovidedthe
2、paradigmforsignalingcompartmentalization.Thedifferentreceptors,chieflytheGPCRs(G-ProteinCoupledReceptors),AlphaandBeta-ADRs(AdrenergicReceptors),GrowthFactorreceptors,CRHR(CorticotropinReleasingHormoneReceptor),GcgR(GlucagonReceptor),DCC(DeletedinColorectalCarcinoma),etcareresponsibleforcAMPaccumu
3、lationincellsthatcausedifferentphysiologicaloutcomes,andchangesincAMPlevelseffectstheselectiveactivationofPKA(cAMPdependentProteinKinase-A)isoforms.ThechiefsourceofcAMPisfromATP(AdenosineTriphosphate).Inmammals,theconversionofATPtocAMPismediatedbymembersoftheClass-IIIAC(AdenylylCyclase)/ADCY(Adeny
4、lateCyclase)family(E.C4.6.1.1),whichinhumanscomprisesninetrans-membraneACenzymesortmACsandonesolubleACorsAC(Ref.1&2).ThesACpredominantlyoccursinmaturespermatozoa.tmACsareregulatedbyheterotrimericG-proteinsinresponsetothestimulationofvarioustypesofGPCRsandthereforeplayakeyroleinthecellularresponset
5、oextracellularsignals.sAC,incontrast,isinsensitivetoG-proteins.Instead,sACisdirectlyactivatedbyCa2+(CalciumIons)andthemetaboliteHCO3-(BicarbonateIons),renderingtheenzymeanintracellularmetabolicsensor.Together,tmACsandsACregulateadiversesetofessentialbiologicalprocesses,suchasdifferentiationandgene
6、transcription,andthismakescAMPsignaling,animportantmediatorofintra-andextracellularsignalsinorganismsfromprokaryotestohighereukaryotes(Ref.2&3).Theextracellularstimulilikeneurotransmitters,hormones,inflammatorystimuli,stress,epinephrine,norepinephrine,etcactivatetheG-proteinsthroughreceptorslikeGP
7、CRsandADR-Alpha/Beta.ThemajorG-proteinsthatregulateactivationofACsaretheGN-AlphaS(GN-AlphaSComplexLocus),GN-AlphaQ(GuanineNucleotide-BindingProtein-Alpha-Q)andGN-AlphaI(GuanineNucleotideBindingProtein-AlphaInhibi
