MSP,macrophage-stimulatingprotein,actsthroughthetransmembranereceptorkinaseRON(Stkinmice)toplayaroleininflammationandtheresponsetotissueinjury.MSPissecretedbytheliverintothebloodaspro-MSP,aninactiveprecursorform.MSPisrelatedtoclottingfactorsthatareactivatedbyproteolyticcleavageandpro-MSPisitselfalsoactivatedbycleavagetoMSP.BindingofactivatedMSPheterodimertoRONexpressedonmacrophages,monocytesandkeratinocytesstimulatesactivationoftheRONkinaseandsecondmessengerpathways,includingPI-3kinase.MacrophagesrespondtoMSPwithchangesincellshapeandmotilityandkeratinocytesrespondbyproliferating.Tissueinjuryleadstopro-MSPcleavageandactivation,andmacrophagesandkeratinocytesthatrespondtoMSParekeycellsintissueinjuryresponse,supportingaroleforMSPandRONintheresponsetotissueinjury.TheinteractionofMSPandmacrophagesatsitesofinflammationsuchasinfectionalsodependsonchemotacticfactorssuchasMCP1andinflammatorycytokinessuchasIL-1andTNFthatattractandactivateimmunecellsintheaffectedtissue. Contributor:GlennCroston,PhD REFERENCES:CorrellPH,IwamaA,TondatS,MayrhoferG,SudaT,BernsteinA.GenesFunct1997Feb;1(1):69-83.DeregulatedinflammatoryresponseinmicelackingtheSTK/RONreceptortyrosinekinase.DanilkovitchA,LeonardEJ.JLeukocBiol1999Mar;65(3):345-8,KinasesinvolvedinMSP/RONsignaling.NanneyLB,SkeelA,LuanJ,PolisS,RichmondA,WangMH,LeonardEJ.JInvestDermatol1998Oct;111(4):573-81,Proteolyticcleavageandactivationofpro-macrophage-stimulatingproteinandupregulationofitsreceptorintissueinjury.