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1、HeinekeJ,MolkentinJDRegulationofcardiachypertrophybyintracellularsignallingpathways.NatRevMolCellBiol20067:589-600Themammalianheartisadynamicorganthatcangrowandchangetoaccommodatealterationsinitsworkload.Duringdevelopmentandinresponsetophysiologicalstimul
2、iorpathologicalinsults,theheartundergoeshypertrophicenlargement,whichischaracterizedbyanincreaseinthesizeofindividualcardiacmyocytes.Recentfindingsingeneticallymodifiedanimalmodelsimplicateimportantintermediatesignal-transductionpathwaysinthecoordinationo
3、fheartgrowthfollowingphysiologicalandpathologicalstimulation.哺乳动物的心脏是一个动力器官，它能够随着工作负荷的增减而进行适应性的改变。在发育过程中，及对生理性刺激或病理性损伤的反应过程中，心脏会经历一个肥大性扩大过程，主要表现为单个心肌细胞体积的增加。在最近的研究工作中发现给予经遗传修饰的模型动物以生理性或病理性刺激后，几条重要的信号传递途径交联对话，共同参与了心脏肥大过程。XinHB,RogersK,QiY,KanematsuT,Fleisc
4、herSThreeaminoacidresiduesdetermineselectivebindingofFK506-bindingprotein12.6tothecardiacryanodinereceptor.JBiolChem1999274:15315-15319FK506-bindingprotein(FKBP12)hasbeenfoundtobeassociatedwiththeskeletalmuscleryanodinereceptor(RyR1)(calciumreleasechannel
5、),whereasFKBP12.6,anovelisoformofFKBP,isselectivelyassociatedwiththecardiacryanodinereceptor(RyR2).ForbothRyRs,thestoichiometryis4FKBP/RyR.AlthoughFKBP12.6differsfromFKBP12byonly18of108aminoacids,FKBP12.6selectivelybindstoRyR2andexchangeswithboundFKBP12.6
6、ofRyR2,whereasbothFKBPisoformsbindtoRyR1andexchangewithboundFKBP12ofRyR1.ToassesstheaminoacidresiduesofFKBP12.6thatarecriticalforselectivebindingtoRyR2,theresiduesofFKBP12.6thatdifferwithFKBP12weremutatedtotherespectiveresiduesofFKBP12.RyR2ofcardiacsarcop
7、lasmicreticulum,prelabeledbyexchangewith[35S]FKBP12.6,wasusedasassaysystemforbinding/exchangewiththemutants.Thetriplemutant(Q31E/N32D/F59W)ofFKBP12.6wasfoundtolackselectivebindingtothecardiacRyR2,comparablewiththatofFKBP12.0.Incomplementarystudies,mutatio
8、nsofFKBP12tothethreecriticalaminoacidsofFKBP12.6,conferredselectivebindingtoRyR2.EachoftheFKBP12.6andFKBP12mutantsretainedbindingtotheskeletalmuscleRyR1.Weconcludethatthreeaminoacidresidues(Gln31,Asn32,andPhe59)ofhu
