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A-RAF Kinase Functions in ARF6 Regulated Endocytic Membrane Traffic 英文参考文献
A-RAFKinaseFunctionsinARF6RegulatedEndocytic
MembraneTraffic
ElenaNekhoroshkova,StefanAlbert,MatthiasBecker,UlfR.Rapp*
Institutfu¨rMedizinischeStrahlenkundeundZellforschung(MSZ),UniversityofWu¨rzburg,Wu¨rzburg,Germany
Abstract
Background: RAF kinases direct ERK MAPK signaling to distinct subcellular compartments in response to growth factor
stimulation.
Methodology/Principal Findings: Ofthethreemammalianisoforms A-RAFis specialinthatone ofitstwolipidbinding
domains mediates a unique pattern of membrane localization. Specific membrane binding is retained by an N-terminal
fragment(AR149)thatcorrespondstoanaturallyoccurringsplicevarianttermedDA-RAF2.AR149colocalizeswithARF6on
tubularendosomesandhasadominantnegativeeffectonendocytictrafficking.Moreoveractinpolymerizationofyeastand
mammaliancellsisabolished.AR149/DA-RAF2doesnotaffecttheinternalizationstepofendocytosis,buttraffickingtothe
recyclingcompartment.
Conclusions/Significance:A-RAFinducedERKactivationisrequiredforthisstepbyactivatingARF6,asA-RAFdepletionor
inhibitionoftheA-RAFcontrolledMEK-ERKcascadeblocksrecycling.ThesedataledtoanewmodelforA-RAFfunctionin
endocytictrafficking.
Citation:NekhoroshkovaE,AlbertS,BeckerM,RappUR(2009)A-RAFKinaseFunctionsinARF6RegulatedEndocyticMembraneTraffic.PLoSONE4(2):e4647.
doi:10.1371/journal.pone.0004647
Editor:HowardRiezman,UniversityofGeneva,Switzerland
ReceivedJuly15,2008;AcceptedJanuary13,2009;PublishedFebruary27,2009
Copyright:?2009Nekhoroshkovaetal.Thisisanopen-accessarticledistributedunderthetermsoftheCreativeCommonsAttributionLicense,whichpermits
unrestricteduse,distribution,andreproductioninanymedium,providedtheoriginalauthorandsourcearecredited.
Funding:ENwassupportedbyDFGgrantRA-642/11-2,Deutsch-Franzo¨sichesGraduiertenkollegGRK1141/1,SFB581ProjectB5andSFB487ProjectC3.MBwas
supported by SFB TR 17 of the DFG. The funders had no role in the study design, data collection and analysis, decision to publish, or preparation of the
manuscript.
CompetingInterests:Theautho
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