Rac-1isasmallG-proteinintheRhofamilythatregulatescellmotilityinresponsetoextracellularsignals.Severalchangesincytoskeletalstructureandotheraspectsofcellstructureareinvolvedincellmotility.Rac-1isactivatedbyGEFfactors,andrepressedbyGAPs.GEFsareguaninenucleotideexchangefactors,includingTrioandVav.Sos-1isinvolvedinRassignalingandalsoactsasaGEFforRactotransducesignalsbetweenRasandRac.SWAP-70isaRacGEFthatbindsIP3andtransducessignalsfromtyrosinekinasestoRactomodulatetheCytoskeletonandcausemembraneruffling.GAPsareGTPase-activatingproteins.Racstimulatestheformationofactin-basedstructuressuchasfilopodiaandlamellopodia,whileGAPssuchaschimerinopposetheformationoftheseRacdependentstructures.SeveraldifferentfactorsdownstreamofRacactoncytoskeletalstructureandotheraspectsofcellmotility.Pak1providesadirectlinkfromRactocellmotilitythroughphosphorylationofthemyosinlightchain.Pak1alsophosphorylatesandactivatesLIMkinase,whichphosphorylatescofilinasonetarget.Cofilinstimulatesactindepolymerizationandchangesincellstructure,andphosphorylationofcofilinbyLIMkinaserepressesitsactivity.Inneurons,Racactsthroughtheproteinkinasecdk5andp35tophosphorylateanddownregulatePak1,increasingneuronalmigration.Rac-1alsointeractswithseveralotherfactorstoregulateavarietyofprocesses.InteractionofPor1withRac-1isinvolvedinmembraneruffling.WAVEisamemberoftheWASPfamilyofproteinsthatregulateactinorganizationandthatisinvolvedinRacsignalingtocausemembraneruffling.InteractionofRac-1withMEKK1integratesRacsignalingwithpathwayssignalingthroughmapkinases. Contributor: REFERENCES:Edwards,D.C.,Sanders,L.C.,Bokoch,G.M.,Gill,G.N.(1999)ActivationofLIM-kinasebyPak1couplesRac/Cdc42GTPasesignalingtoactincytoskeletaldynamics.NatCellBiol1(5),253-9K.Rottner,A.HallandJ.V.Small,InterplaybetweenRacandRhointhecontrolofsubstratecontactdynamics.CurrentBIOLOGy,1999,vol9no13,640-648.Miki,H.,Suetsugu,S.,Takenawa,T.(1998)WAVE,anovelWASP-familyproteininvolvedinactinreorganizationinducedbyRac.EMBOJ17(23),6932-41Nikolic,M.etal.(1998)Thep35/Cdk5kinaseisaneuron-specificRaceffectorthatinhibitsPak1activity.Nature395(6698),194-8Sells,M.A.,Boyd,J.T.,Chernoff,J.(1999)p21-activatedkinase1(Pak1)regulatescellmotilityinmammalianfibroblasts.J.Cell.Biol.145(4),837-49Shinohara,M.etal.(2002)SWAP-70isaguanine-nucleotide-exchangefactorthatmediatessignallingofmembraneruffling.Nature416(6882),759-63VanAelst,L.,Joneson,T.,Bar-Sagi,D.(1996)IdentificationofanovelRac1-interactingproteininvolvedinmembraneruffling.EMBOJ15(15),3778-86Yang,N.etal.(1998)CofilinphosphorylationbyLIM-kinase1anditsroleinRac-mediatedactinreorganization.Nature393(6687),809-12