Signal Transduction II

《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),