通过膜受体的信号传递

通过膜受体的信号传递途径SIGNALTRANSDUCTIONQUESTIONHowdovariouscellsinanmulticellurorganismcoordinatewitheachother?Howanextracellularsignal,suchasahormone,influenceintracellularevents?

Cellsignaling细胞信号传递:

Cellsuseavarietyofdifferentreceptor(受体）

proteinstoreceiveandrespondtosignalsfromtheexternalenvironment.Thebindingofthesignalingmolecule（suchasahormone，growthfactor，orneurotransmitter（激素、生长因子、神经递质等））tothereceptorresultsinacascadeofenzymaticreactions（级联酶促反应）

insidethecellthatconstitutestheappropriateresponsetothesignal.Definition（一）cAMP-蛋白激酶途径

cAMP-ProteinkinasePathway

----（腺苷酸环化酶体系）adenylatecyclasesystem

SomeHormonesgothroughthispathway: eg:Glucagon(胰高血糖素)Adrenalin/Epinephrine(肾上腺素)

Antidiuretin

(抗利尿激素,ADH)

信息传递简式：HormoneMembranereceptorG-proteinACcAMPPKAFunctionalproteinBiologicaleffectP腺苷酸环化酶Adenylatecyclase蛋白激酶AProteinkinaseAResultchangesincAMPlevels,activatingtargetproteinssuchasproteinkinaseA（蛋白激酶A）.改变cAMP浓度，激活蛋白激酶ATheMainCharacteristic(主要特征)：Sevenmembrane-spanningαhelicsreceptorB.TrimericG-Protein（三聚体G蛋白）-subunit-subunit-subunitReceptorandThetrimericG-proteinStimulatoryGProtein(激活型G蛋白)RssGDPGTPGDP5’-AMPPhosphodiesteraseACcAMPATPPpisGTP+ActivatePKAPhospho-rylationofcellularproteinsbyPKAcausesthecellularresponseGiRiRiInhibitoryGProtein(抑制型G蛋白)IGDPGTPGDPIGTP+ACATPcAMPPpi2.cAMP和蛋白激酶A

cAMPandProteinkinaseAcAMP

cAMP(cyclicAMP)isanucleotidesecondmessengerthatparticipatesinmanyGproteinsignalingcascades.

Second-messenger

(第二信使):Thesecond-messengersystemisasetofintracellularmoleculesthatareactivatedbycellsurfacereceptorsandaffectcellfunction,producingaphysiologicalresponse.第二信使是被膜受体激活的胞内分子，通过浓度变化传递信号，影响细胞功能。胞外的各种信号转换成胞内单一的信号，细胞只需读取这个第二信号，作出应答ATPcAMPAdenylatecyclasePhosphodiesterase磷酸二酯酶5’-AMPProteinkinaseA(蛋白激酶A):IsacAMP–dependentproteinkinase

依赖cAMP的蛋白激酶cAMPisitsallostericactivator

cAMP是蛋白激酶A的变构激活剂。cAMPandProteinkinaseA

----AllostericRegulation4XcAMP4XcAMPAmplification(moleculesconverted)AdrenalinATPcAMPGlycogenGlucose1-phosphatePKAPKAProteinkinaseAPKPKPhosphorylasekinasebGPbGPaGlucogenphosphorylaseGlucoseGs1moleculesAdenylatecyclase40molecules10molecules100molecules1,00010,000（二）cGMP-蛋白激酶途径

cGMP-Proteinkinasepathway

Somesignalmoleculesusethispathway:

Insulin(胰岛素),

Atriopeptins(心房肽)，

Acetylcholine(乙酰胆碱)，

Nitricoxide(NO)

……

简图HormoneMembranereceptorG-proteinGCcGMPPKGFunctionalproteinBiologicaleffectP鸟苷酸环化酶Guanylatecyclase蛋白激酶GProteinkinaseGGlonoin硝酸甘油NOThefunctionofcGMPisusuallytheoppositeofcAMP.CyclicGMP/cGMPcGMPisanintracellularsecondmessenger,producedfromthecyclizationofGTPinanintramolecularreactioncatalyzedbyguanylatecyclase(鸟苷酸环化酶).TherisinglevelofcGMPcanactivateacGMP-dependentproteinkinase(PKG,蛋白激酶G)thatisinvolvedinrelaxingsmoothmusclecells

Question

Wehavelearnedthatthebindingofaligandtoaproteinisthechemicalfoundationofproteinfunction.Whichstepsinthesignalingpathwaywehavejustlearnedbelongtothebindingofligandsandproteins?Isitpossiblethatchinesemedicineaffectthissignalingpathway?DrugsandToxinsThatAffect

thisCellSignalingPathwayCaffeine(咖啡因),theophylline(茶碱),andtheobromine(可可碱)arestimulants,inpart,becausetheyinhibitcAMPphosphodiesterase.Choleratoxin(霍乱毒素)

canactivateGs-protein,andthusAC.Pertussistoxin(百日咳毒素)caninhibitGi-protein,andthereforecannotinhibitAC.（三）Ca2+-依赖性蛋白激酶途径

CalciumIon–DependentProteinKinasePathwey

1.Hormoneswhichgothroughthispathway:

促甲状腺素释放激素Thyrotropin-releasinghormone、去甲肾上腺素Noradrenalin血管紧张素ⅡAngiotensinⅡ加压素Pitressin胃泌素Gastrin……

打开Ca2+通道激活PKCHormoneReceptor受体GProteinG蛋白GqPLC(磷脂酶C)PIP2IP3(肌醇三磷酸)DAG(二酰甘油)各种生物学效应磷脂酰肌醇循环PhosphotidylinositolcyclePhosphotidylinositol磷脂酰肌醇PIIP3CH2

OCR1CH2

OHR2CO

CHOODAGCH2

OCR1CH2

OPOR2CO

CHOOOOHCH2

OCR1CH2

OPOR2CO

CHOOOOHPIP2IIPPIPPP2.磷脂酶C型G蛋白(PLCG-protein，Gp)的激活Pip+GTPpp3.第二信使的作用﹡IP3

(inositoltrisphosphate肌醇三磷酸)

：Bindthereceptorinthemembraneofthesmoothendoplasmicreticulum(内质网)andmitochondria(线粒体)，opencalciumchannels.Calciumionsfloodintothecytosol,leadingtocellularresponses.

与内质网、线粒体膜特异受体结合，打开钙库,释放大量Ca2+,引起生物效应.如:糖原分解(glycogenolysis)↑。﹡DAG(diacylglycerol二酰甘油)：ActivatePKC,whichphosphorylatemanyotherproteins

,changingtheircatalyticactivities,leadingtocellularresponses.

激活PKC,后者使相应的酶磷酸化而激活或抑制。如:糖原合成(glycogenesis)↓。﹡Ca2+：

(1)CooperatewithDAGinactivatingPKC(蛋白激酶C)

配合DAG激活PKC

(2)ActivateCaMkinasepathway,inwhichcalmodulin(钙调蛋

白)bindsCa2+,undergoesachangeinconformation,and

activatesCaMkinase.Thekinasethenphosphorylates

targetenzymes,regulatingtheiractivities.

Ca2+-CaMisalsoaregulatorysubunitofadenylate

cyclase(腺苷酸环化酶)andphosphodiesterase(磷酸二酯酶).

4. 该途径最终引发生物效应的酶：

ProteinkinaseC(蛋白激酶C)

Ca2+

-CaMProteinkinase

(Ca2+-CaM蛋白激酶)Ca2+,钙调蛋白与Ca2+-CaM蛋白激酶的结合

ThebindingofCa2+,calmodulinandCa2+-CaMProteinkinase小结：该途径的信息传递过程简图:Ip3

→ReleasingCa2+→Ca2+-CaM→→PIP2→DAG——→

PKC————→GqPhospho-rylationoffunctionalproteinsBiologicaleffectsPhospho-rylationoffunctionalproteinsBiologicaleffectsHormonereceptorSummary

H1HRＧ

Adenylatecyclase

cAMP

PKA

H2HRＧ

Gua