AngIIbindingtoAT1-RtriggerstheactivationofCa2+signalingandPKC.ThesignalisthentransmittedtothePyk2andfurthertothesmallGproteinRac1butnotCdc42,althoughthedirectactivationofRac1byPyk2isnotprovedinthisstudy.Inturn,Rac1activatesasmallGprotein-activatedkinasewhoseidentityisstillcontroversial,butoneofwhichhasbeensuggestedtobePAK1.Finally,theJNKcascade,includingMEKK1,SEK1,andJNK,isactivated,causinginductionofc-JungeneviabindingofATF2andc-JunheterodimertothejunTRE2site.AngIIiscloselyinvolvedinthecardiacremodelingbystimulatingsynthesisofextracellularmatrixproteins.ItwasrecentlyfoundthatexpressionoffibronectinbyAngIIistranscriptionallyregulatedbyAP-1complexincardiacfibroblasts.CollagenasegenecontaingAP-1sitesisalsoregulatedbyAP-1componentsincludingc-Jun.AP-1activityisalsoenhancedinAngII-inducedcardiachypertrophy.ExpressionofANFisregulatedbyAP-1components.

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REFERENCES:SatoshiMurasawa,etal.AngiotensinIIInitiatesTyrosineKinasePyk2-dependentSignalingsLeADIngtoActivationofRac1-mediatedc-JunNH2-terminalKinase.JournalofBIOLOGicalChemistry,2000,275(35),26856-26863.

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