G-Protein Coupled Receptor Signaling Architecture of Mammalian Immune Cells 英文参考文献.docVIP

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G-Protein Coupled Receptor Signaling Architecture of Mammalian Immune Cells 英文参考文献.doc

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G-Protein Coupled Receptor Signaling Architecture of Mammalian Immune Cells 英文参考文献

G-ProteinCoupledReceptorSignalingArchitectureof MammalianImmuneCells NataliaPolouliakh1,2,RichardNock3,FrankNielsen1,HiroakiKitano1,2* 1SonyComputerScienceLaboratoriesInc.,Tokyo,Japan,2SystemsBiologyInstitute,Tokyo,Japan,3CEREGMIA-Univ.Antilles-Guyane,Schoelcher,France Abstract A series of recent studies on large-scale networks of signaling and metabolic systems revealed that a certain network structureoftencalled‘‘bow-tienetwork’’areobserved.Insignalingsystems,bow-tienetworktakesaformwithdiverseand redundantinputsandoutputsconnectedviaasmallnumbersofcoremolecules.Whileargumentshavebeenmadethat suchnetworkarchitectureenhancesrobustnessandevolvabilityofbiologicalsystems,itsfunctionalroleatacellularlevel remainsobscure.Ahypothesiswasproposedthatsuchanetworkfunctionasastimuli-reactionclassifierwheredynamicsof coremoleculesdictatedownstreamtranscriptionalactivities,hencephysiologicalresponsesagainststimuli.Inthisstudy,we examinedwhethersuchhypothesiscanbeverifiedusingexperimentaldatafromAllianceforCellularSignaling(AfCS)that comprehensivelymeasuredGPCRrelatedligandsresponseforB-cellandmacrophage.InaGPCRsignalingsystem,cAMP 2+ and Ca act as core molecules. Stimuli-response for 32 ligands to B-Cells and 23 ligands to macrophages has been measured. Wefound thatligands withcorrelated changes of cAMP andCa tendtocluster closely togetherwithin the 2+ hyperspacesofbothcelltypesandtheyinducedgenesinvolvedinthesamecellularprocesses.Itwasfoundthatligands inducingcAMPsynthesisactivategenesinvolvedincellgrowthandproliferation;cAMPandCa2+moleculesthatincreased togetherformafeedbackloopandinduceimmunecellstomigrateandadheretogether.Incontrast,ligandswithoutacore molecules response are scattered throughout the hyperspace and do not share clusters. G-protein coupling receptors togetherwithimmune responsespecific receptors werefoundincAMP andCa2+ activated clusters. Analyses havebeen done on the original software applicable for discovering ‘bow-tie’ network architectures within th