N‐terminal PH domain and C‐terminal auto‐inhibitory region of CKIP‐1 coordinate to determine its nucleus‐plasma membrane shuttling

摘要

Thepleckstrinhomology(PH)domain‐containingproteincaseinkinase2interactingprotein‐1(CKIP‐1)playsanimportantroleinregulationofboneformationandmuscledifferentiation.HowCKIP‐1localizationisdeterminedremainslargelyunclear.WeobservedthatisolatedCKIP‐1‐PHdomainwaspredominantlylocalizedinthenucleusandtheC‐terminusofCKIP‐1counteracteditsnuclearlocalization.Thenetchargeofbasicresiduesandaserine‐richmotifwithinthePHdomainplaysapivotalroleinthelocalizationswitchofbothfull‐lengthCKIP‐1andtheisolatedPHdomain.WeproposethattheN‐terminalPHdomainandC‐terminalauto‐inhibitoryregionofCKIP‐1coordinatetodetermineitssubcellularlocalizationandthenucleus–plasmamembraneshuttling...