细胞信号转导英文版ppt课件

Chapter15CellularSignalTransduction ThebiochemistryandmolecularbiologydepartmentofCMU Whenenvironmentchanges Monad respondsdirectly Multicellularorganisms signalthroughelaboratesystemofintercellularorintracellularcommunication andconsequentlyregulatefunctionsoforganisms Signalingmolecule Receptoroftargetcell Intracellularmolecule biologicaleffect Signaltransduction 1SignalingMolecules Signalingmolecules Signalingmolecules whicharereleasedbysignal producingcells reachandtransferbiologicalsignalstotheirtargetcellstoinitiatespecificcellularresponses ExtracellularmoleculesIntracellularmolecules 1 Extracellularmolecules protein peptides Hormone cytokineAA itsderivatives Gly Glu adrenaline thyroxineSteroid SexHormone glucocorticosteroidFattyacidderivatives prostaglandin 1 Paracrinesignaling localchemicalmediators Secretedbycommoncells Reachneighboringtargetcellsbypassivediffusion Timeofactionisshort SuchasGF PG 2 Endocrinesignal Secretedbyendocrinecells Reachtargetcellsbybloodcirculation Timeofactionislong Suchasinsulin thyroxine adrenalin 3 Synapticsignal neurotransmitters Secretedbyneuronalcells Reachanotherneuronbysynapticgap Timeofactionisshort SuchasAcetylcholine Ach noradrenaline 4 Gaseoussignal Simplestructure halflifeisshortandactiveinchemistry SuchasNO CO GASMOLECULE 5 Autocrinesignal Actbacktotheirowncells SuchasGF cytokine interferon interleukin 2 Intracellularmolecule Ca2 ionsDG ceramidelipidderivativesIP3carbohydratederivativescAMPcGMPnucleotidesRas JAK Rafproteins Secondmessenger Smallmoleculessynthesizedincellsinresponsetoanexternalsignalarethesecondmessengers whichareresponsibleforintracellularsignaltransduction SuchasCa2 DG Cer IP3 cAMP cGMP Thirdmessengers Thirdmessengersarethemoleculeswhichtransmitmessagefromoutsidetoinsideofnucleousorfrominsidetooutsideofnucleous alsocalledDNAbindingprotein Effectbymembranereceptors Effectbyintracellularreceptors Intracellularmolecules Extracellularmolecules Signalmolecules cAMP cGMP IP3 DG Ca2 Proteinsandpeptides Hormones cytokines Aminoacidderivatives Catecholamines Fattyacidderivatives Prostaglandins Steroidhormones Thyroxine VD3 2Receptor Receptor Receptorsarespecificmembraneproteins whichareabletorecognizeandbindtocorrespondingligandmolecules becomeactivated andtransducesignaltonextsignalingmolecules GlycoproteinorLipoprotein ligandAsmallmoleculethatbindsspecificallytoalargerone forexample ahormoneistheligandforitsspecificproteinreceptor MembranereceptorsmembraneGlycoproteinIntracellularreceptorsCytosolornucleiDNAbindingprotein 1 Ligand gateionchannelstype cyclicreceptor ligand receptor ionchannelopenorclose 1 membranereceptors 1 7 helicestransmembranereceptor 2 GProtein CoupledReceptors serpentineR GproteinreferstoanyproteinwhichbindstoGDPorGTPandactassignaltransduction Gproteinsconsistofthreedifferentsubunits subunit subunitcarriesGTPaseactivity bindingandhydrolysisofGTP 2 Gprotein Guanylatebindingprotein Gs s AC cAMP Gi i AC cAMP Gq q PI PLC IP3 DAGGo o ionchannelGt t cGMPPDE cGMP Rhodopsin 3 ClassesofGprotein Glucagon adrenaline s AC ACTH adrenalineangiotensin acetylcholine M2M4 GFreleaseinhibitoryfactor i AC RibosylationofArgofG G s ATP G s ADP AC cAMP Cl H2O Cavityofintestinediarrhea HCO3 Choleratoxin ATPase Pertussistoxin i ADP ribosylationGiAC allergyofhistamine cAMP ACcGMPPDE phosphodiesterase PLCPLA2Channelprotein 4 EffectproteinsofGprotein cAMP ATP 5 PathwayofGproteinlinkedreceptor H R Gprotein Es secondarymesseger Proteinkinase PhophorylationofEsorfunctionalprotein Biologicaleffect 3 Singletransmembrane helixreceptor TyrosineproteinkinaseReceptor catalyticreceptor IGF R EGF RNontyrosineproteinkinaseReceptorGrowthHormoneR interferonR TyrosineproteinkinaseReceptororreceptortyrosinekinase RTK Intracellularinsulineffects Cytosol Insulin Non receptortyrosinekinase NRTK DomainofDownstreammoleculesofTPKR SH2domain Scrhomology2domain SH3domainPHdomain pleckstrinhomologydomain Membranereceptor ANPSolublereceptor NO CO 4 Guanylatecyclase GC receptor 2 Intracellularreceptor transcriptionregulatedreceptor IntracellularRistrans actingelememtcis actingelementgeneexpressionLocalizedinthecytosoland orinthenucleus ligand SteroidH VD3 Thyroxine 3 PropertiesofbindingofHandR highlyspecificityhighlyaffinitysaturationreversiblebindingspecialfunctionmodel 4 Controlofreceptoractivity PhosphorylationordephosphorylationofRPhospholipidofmembraneEnzymecatalyzedhydrolysisGproteinregulation 1 Recognizethespecialligand 2 Bindingtospecialligand 3 Signaltransductionbiologicaleffect 5 Functionofreceptor 3PathwayofSignalTransduction Signaltransductionmediatedbymembranereceptor cAMPdependent proteinkinaseApathwaycGMPdependentPKGpathwayCa2 dependentPKpathwayTyrosineproteinKinasepathwayNF BpathwayTGF pathway 1 cAMPdependent proteinkinaseApathway H R Gprotein PhosphorylationofEsorfunctionalproteins Biologicaleffects PKA cAMP AC 1 cAMPmetabolism AC PDE AC Adenylatecyclase PDE Phosphodiesterase 2 MechanismofcAMPeffect ActivatecAMP dependentproteinkinase PKA 3 PKAeffect PhosphorylatespecificallySer Thrresiduesinseveralproteins 1 Regulationofmetabolism 2 Regulationofgeneexpression CRE cAMPresponseelement TGACGTCA CREB CREbindingprotein DNA CREB PKA Transcription mRNA CREB PKA 2 Ca2 dependentPKpathway 1 Ca2 DAG dependentPKCpathway H R PIP2 Gprotein PLC IP3 DG ER PKC Ca2 PS Biologicaleffects PhosphorylationofEsorfunctionalproteins Ca2 i0 01 1 mol L 10 7mol L Ca2 o2 5mmol L 10 3mol L 5000 10000 1 FunctionofDGandIP3 IP3 R openofCa2 channel Ca2 PS Ca2 DG PKC 2 FunctionofPKC regulationofmetabolismPKC Ser Thr PofR enzyme ProteinofMb Geneexpression Lateresponse Trans actingfactor P Thirdmessenger Immediateearlygenes Thirdmessenger P Activategenes Cellproliferation PKC PKC Earlyresponse 2 Ca2 CaMdependentproteinkinasepathway H R Gprotein PLC IP3 Ca2 CaM CaMK Biologicaleffects PhosphorylationofEsorfunctionalproteins Calmodulin CaM Ca2 bindingprotein4Ca2 CaM Ca2 CaM CaMkinase Ser Thr P Ca2 pump AC GC Es glycogensynthase phosphorylasekinase 3 cGMP dependentPKGpathway Biologicaleffects PhosphorylationofEsorfunctionalproteins ANP NO CO SolubleGC PKG cGMP Receptor linkedGC 1 cGMP 2 FunctionofPKGSer Thr PofproteinandE GC PDE GC Guanylatecyclase ANP atrialnatriureticpeptides GCNO cGMP PKG Vasculardilatation 4 Tyrosine proteinkinasepathway TPK TPKreceptorisrelatedtoproliferation differentiation dissociation carcinomatouschange TPK receptorTPK Mb nonreceptorTPK cytosol 1 ReceptorTPK Ras MAPKpathway GRB2 SOS Ras RafSmallGprotein R