PhospholipaseC(PLC)d1isamemberofthePLCfamilythatproducestwosecondmessengers,diacylglycerol(DAG)andinositol1,4,5-triphosphate(IP3)byhydrolyzingthemembranelipidphosphatidylinositol4,5-bisphosphate(PIP2).DAGincombinationwithCa++isnecessaryforfurtheractivationofProteinKinaseC,whileIP3diffusesintothecytoplasmandmediatesthereleaseofintracellularcalcium.PLCd1hasapleckstrinhomology(PH)domainthatbindstoPIP2inthemembranewithanaffinityof1.7mM.IthasselectivityforPIP2overotherphosphatidylinositollipidsandprovidesaspecificprobeforactivationofPIP2metabolismtoDGandIP3.ActivationofPLCd1resultsinitstranslocationfromthemembranetothecytoplasm.PLCd1activityisfeedback-inhibitedbyIP3,whichhasa8-foldhigheraffinityforPLCd1thandoesPIP2.ThemembersofthePLCfamilyplayakeyroleinthesignaltransductioncascadeformanyreceptors.AtbasalCa++levelsPLCd1hasbeenshowntobeactivatedbytheadrenoreceptora1B,adrenoreceptora1D,a-thromboxanereceptorandoxytocinreceptor.TheGproteininvolvedistheGTP-bindingproteinknownastissuetransglutaminase(GahorTGII).Gahisabifunctionalenzyme,havingGTPaseandtransglutaminase(TGase)activityandispresentintheplasmamembrane,cytosol,andnucleus.ExchangeofGDPtoGTPbyGahisfacilitatedbyactivationofthereceptors.However,abimodalregulationofPLCd1activityhasbeenobserveddependingonCa++levelsandoccupancyoftheguaninenucleotidebindignsiteofGah.Inaddition,theGTPaseactivatingproteinRhoGAPinteractswithandstimulatesPLCd1.ThecomplexregulationofPLCd1activityenablestheproteintomodulateintracellularsignaling.

Contributor:

REFERENCES:BaekKJ,KangS,DamronDandImM(2001)PhospholipaseCdelta1IsaGuanineNucleotideExchangingFactorforTransglutaminaseII(GalphaH)andPromotesAlpha1B-Adrenoreceptor-MediatedGTPBindingandIntracellularCalciumRelease.JBiolChem276:pp5591-5597.KavranJM,KleinDE,LeeA,FalascaM,IsakoffSJ,SkolnikEYandLemmonMA(1998)SpecificityandPromiscuityinPhosphoinositideBindingbyPleckstrinHomologyDomains.JBiolChem273:pp30497-30508.LemmonMAandFergusonKM(2000)Signal-DependentMembraneTargetingbyPleckstrinHomology(PH)Domains.BiochemJ350Pt1:pp1-18.MurthySNandLorandL(2000)NucleotideBindingbytheErythrocyteTransglutaminase/GhProtein,ProbedWithFluorescentAnalogsofGTPandGDP.ProcNatlAcadSciUSA97:pp7744-7747.MurthySN,LomasneyJW,MakECandLorandL(1999)InteractionsofG(h)/TransglutaminaseWithPhospholipaseCdelta1andWithGTP.ProcNatlAcadSciUSA96:pp11815-11819.MurthySN,WilsonJH,LukasTJ,VeklichY,WeiselJWandLorandL(2000)Transglutaminase-CatalyzedCrosslinkingoftheAalphaandGammaConstituentChainsinFibrinogen.ProcNatlAcadSciUSA97:pp44-48.RheeSGandBaeYS(1997)RegulationofPhosphoinositide-SpecificPhospholipaseCIsozymes.JBiolChem272:pp15045-15048.SekimataM,KabuyamaY,EmoriY,HommaY(1999)MorphologicalChangesandDetachmentofAdherentCellsInducedbyp122,aGTPase-activatingProteinforRho.JBiolChem274:pp17757-17762.VancurovaI,MiskolciV,DavidsonD(2001)NF-kappaBactivationintumornecrosisfactoralpha-stimulatedneutrophilsismediatedbyproteinkinaseCdelta.CorrelationtonuclearIkappaBalpha.JBiolChem276:pp19746-19752

================  蚂蚁淘在线  ================

免责声明：本文仅代表作者个人观点，与本网无关。其创作性以及文中陈述文字和内容未经本站证实，对本文以及其中全部或者部分内容、文字的真实性、完整性、及时性本站不做任何保证或承诺，请读者仅作参考，并请自行核实相关内容

版权声明：未经蚂蚁淘在线授权不得转载、摘编或利用其他方式使用上述作品。已经经本网授权使用作品的，应该授权范围内使用，并注明“来源：蚂蚁淘在线”。违反上述声明者，本网将追究其相关法律责任。