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ID:40812356
大小:1.29 MB
页数:81页
时间:2019-08-08
《Signal Transduction II》由会员上传分享,免费在线阅读,更多相关内容在行业资料-天天文库。
1、SignalTransductionIIBICH202SignaltransductionthroughtheMAPKpathways•Protein-proteininteractions•Proteinkinasecascades.OverviewTheMAPKsignallingpathways•Cellsinanorganismreceiveavarietyofextracellularstimuliforcellproliferation.•Thebestcharacterizedmitogenicpath
2、wayisthemitogen-activatedproteinkinase(MAPK)cascades.•ManygrowthstimulationconvergesonthekinasecascadethatactivatestheMAPK(alsocalledERK1andERK2=extracellularsignal-regulatedkinase1and2).TheMAPKsignallingpathways•TheRAS-activatedMAPKpathway:RAS➙RAF➙MEK➙MAPKrepr
3、esentsthefirstexamplewhereallthestepsinacompletesignallingcascadefromthecellsurfacereceptorPTK,tothenucleartranscriptionisknown.•Uponactivation,MAPKthentranslocateintothenucleusandinducethetranscriptionoftheimmediateearlygenes(e.g.MYC).•Immediateearlygenes:gene
4、sthatareexpressedearlyduringstimulation(incontrasttolateresponsegenes).TheyareusuallytranscriptionfactorsTheMAPKsignallingpathways•ItshouldbenotedthattheRAS-RAF-MEK-MAPKpathwayisonlyoneexampleofsocalled“MAPKpathways”.•TwoothermammalianMAPKpathwaysinvolvingJNK1a
5、ndp38,areinvolvedinstressresponses(theyarealso“MAPKpathways).TheMAPKsignallingpathwaysRAS-RAF-MEK-MAPK•LigandbindsreceptorPTK•LigandbindsreceptorPTK•AutophosphorylationontyrosinePPPPRAS-RAF-MEK-MAPK•LigandbindsreceptorPTK•Autophosphorylationontyrosine•GRB2(aSH2
6、-andSH3-containingprotein)bindstothereceptorphosphotyrosinemotifY-V/L-N-XviaitsSH2domainPPPPRAS-RAF-MEK-MAPKSH2SH3GRB2SOS•LigandbindsreceptorPTK•Autophosphorylationontyrosine•GRB2(aSH2-andSH3-containingprotein)bindstothereceptorphosphotyrosinemotifY-V/L-N-Xviai
7、tsSH2domain•TheSH3ofGRB2bindsconstitutivelytotheproline-richsequenceintheC-terminusofSOS(aguaninenucleotideexchangefactorforRAS).PPPPSH2SH3GRB2SOSRAS-RAF-MEK-MAPK•RecruitmentofSOStothecloseproximityofRASinthemembranePPPPSH2SH3GRB2SOSRASGDPRAS-RAF-MEK-MAPK•RASbe
8、comesactivatedbyexchangingGDPforGTPPPPPSH2SH3GRB2SOSGDPGTPRASRAS-RAF-MEK-MAPKGTP•TheRAS-GTPinteractswiththeN-terminalregulatoryregionoftheRAF(serine/threonineproteinkinase),
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