Ephkinasesareafamilyofreceptortyrosinekinaseswithanextracellulardomainthatbindstheirligand,theephrins,andanintracellularkinasedomain.Theephrinsarealsoexpressedonthecellsurface,sothatinteractionbetweenEphkinasesandephrinsoccursattheinterfacebetweenneighboringcells.BindingofephrinstoEphkinasesstimulatessignalinginbothdirectionsacrosstheinterfacebetweencells,inboththereceptorexpressingandtheligandexpressingcells.EphkinasesandephrinsareinvolvedinseveralBIOLOGicalprocesses,andtheirroleinneuronaldevelopmenthasbeenextensivelyexamined.BothEphkinases(EphA4andEphB1)andephrins(ephrinB1)areexpressedonplatelets,suggestingactivationofephkinasesbyephrinsmayplayaroleinclottingwhenplateletsarebroughtintocloseproximityinthedevelopingclot.PlateletactivationprogressesinstageswithanearlystagethatisstimulatedbysolublefactorslikeADPactingthroughGPCRsandisreversIBLeandlaterstageswithstrongerinteractionbetweenplateletsthatmayrequireinteractbetweenEphkinasesandephrins.OneofthemoleculartargetsofsignalingbyEphkinasesandephrinsistheactinCytoskeleton,whichalsoplaysaroleinplateletactivation.ClusteringEphkinasesorephrinsinplateletsstimulatedcytoskeletalchangesaswellasotherMarkersofplateletactivationduringclottingsuchassecretionofalpha-granulestoreleaseclottingfactors.ClusteringephrinstogetheractivatedRap1b,arasgenefamilymemberthatmayregulateintegrins.PlateletactivationcausedEphkinasestobindtosrcfamilymembersFynandLynandalsowiththecelladhesionmoleculeL1.Failureoftheephrins/Ephkinasepathwaytofunctionnormallyinplateletsmayresultinlooselyassociatedplateletsandimproperclotformation.Ephkinasesandephrinsarealsoexpressedonthevascularwallbyendothelialcells,suggestingthatsignalingbytheseproteinsmayalsoplayaroleintheinteractionofplateletswiththevascularwallandclotformationinthevasculature.

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REFERENCES:Cowan,C.A.andHenkemeyer,M.Ephrinsinreverse,parkanddrive.TrendsincellbiologyVol.12No.7july2002.PrevostN,WoulfeD,TanakaT,BrassLF.InteractionsbetweenEphkinasesandephrinsprovideamechanismtosupportplateletaggregationoncecell-to-cellcontacthasoccurred.ProcNatlAcadSciUSA.2002Jul9;99(14):9219-24.ReedquistKA,RossE,KoopEA,WolthuisRM,ZwartkruisFJ,vanKooykY,SalmonM,BuckleyCD,BosJL.ThesmallGTPase,Rap1,mediatesCD31-inducedintegrinadhesion.JCellBiol.2000Mar20;148(6):1151-8.

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