信号通路和肿瘤.ppt

信号通路和肿瘤引言：细胞信号转导与生命过程——问题提出和理论产生细胞信号转导理论概述信号转导研究中重大理论问题及热点领域信号转导研究方法与工具信号转导理论研究及应用举例：在肿瘤发生发展中信号转导意义信号转导与肿瘤临床：诊疗和治疗细胞信号转导经典文件举例引言细胞信号转导理论建立以前细胞生物学组织生长需要信号通路和肿瘤信号通路和肿瘤细胞信号转导理论概述信号通路和肿瘤胞外信号分子(可溶性分子、细胞表面分子、组织基质分子)ExtracellularSignalMoleculesSignalTransducingReceptors2.Receptorsthatarecoupled,insidethecell,toGTP-bindingandhydrolyzingproteins(G-proteins).e.g.,adrenergicreceptors,odorantreceptors,andcertainhormonereceptors(e.g.glucagon,angiotensin,vasopressinandbradykinin).3.Receptorsthatarefoundintracellularlyanduponligandbindingmigratetothenucleuswheretheligand-receptorcomplexdirectlyaffectsgenetranscriptione.g.,STAT1,3,4,5,6…(Signaltransducerandactivatoroftranscription)4.Simplereceptors:e.g.,ion-channelsthatleadtochangesinmembraneelectricpotential信号转导过程中生物化学SignalTransducersClassNon-ReceptorProteinTyrosineKinases(PTKs)Twonon-receptorPTKfamilies:1)ThearchetypaplPTKfamilty:Src-relatedproteins2)Januskinase(Jak)family信号通路和肿瘤信号通路和肿瘤ReceptorSerine/ThreonineKinases(RSTKs)信号通路和肿瘤Non-ReceptorSerine/ThreonineKinases1)cAMP-dependentproteinkinase(PKA)2)ProteinkinaseC(PKC)3)Mitogenactivatedproteinkinases(MAPKorERK)(requiringphosphorylationofbothtyrosineandthreonine)G-ProteinCoupledReceptors1.>1000GPCRs,mostofwhichareorphanreceptors)2.ThreedifferentclassesofGPCR:GPCRsthatmodulateadenylatecyclaseactivityandproducecAMPGPCRsthatactivatePLC-gleadingtohydrolysisofpolyphosphoinositides:angiotensin,bradykininandvasopressinreceptors.PhotoreceptorIntracellularHormoneReceptors1.Residingwithinthecytoplasm.胞外信号分子(可溶性分子、细胞表面分子、组织基质分子)信号转导研究中重大理论问题及热点领域信号转导通路调控Cross-Talk信号转导效应特异性WhenandWhere??????替换通路（AlternativePathways)信号转导研究方法与工具一、蛋白质磷酸化状态检测1、免疫印迹(phospho-proteinspecificantibodies)2、免疫沉淀(protein-specificantibody+phospho-AAantibody3、流式细胞仪分析4、Luminex分析二、信号转导分子过分表示或过分激活1、Overexpressionbygenetransduction2、Constitutivelyactivatedmutants三、基因转录活性测定1、Electrophoreticmobilityshiftanalysis(EMSA)２、Reportergeneexpressiondetection四、信号转导分子表示或活性抑制1、Anti-sense2、RNAi3、Geneknock-out4、DominantnegativemutantsLigand