The novel ankyrin-repeat containing kinase ARCK-1 acts as a suppressor of the Spalten signaling pathway during Dictyostelium development

摘要

Spalten(Spn),amemberofthePP2CfamilyofSer/Thrproteinphosphatases,isrequiredforemDictyostelium/emcell-typedifferentiationandmorphogenesis.Wehaveidentifiedanewproteinkinase,ARCK-1,throughasecondsitesuppressorscreenformutantsthatallowemspn/emnullcellstoproceedfurtherthroughdevelopment.ARCK-1hasaC-terminalkinasedomainmostcloselyrelatedtoSer/ThrproteinkinasesandanN-terminalputativeregulatorydomainwithankyrinrepeats,a14-3-3bindingdomain,andaC1domain,whichisrequiredforbindingtoRasBsupGTP/supinatwo-hybridassay.DisruptionofthegeneencodingARCK-1resultsinweak,latedevelopmentaldefects.However,overexpressionofARCK-1phenocopiestheemspn/emnullphenotype,consistentwithSpnandARCK-1beingonthesamedevelopmentalpathway.OurpreviousanalysesofSpnandthepresentanalysisofARCK-1suggestamodelinwhichSpnandARCK-1differentiallycontrolthephosphorylationstateofaproteinthatregulatescell-typedifferentiation.DephosphorylationofthesubstratebySpnisrequiredforcell-typedifferentiation.ControlofARCK-1andSpnactivitiesbyupstreamsignalsisproposedtobepartofthedevelopmentalregulatoryprogrammediatingcell-fatedecisionsinemDictyostelium/em./p/div