Phosphoinositide3-kinase(PI(3)K)isauniqueenzymecharacterizedbybothlipidandproteinkinaseactivities.Here,wedemonstratearequirementfortheproteinkinaseactivityofPI(3)Kinagonist-dependent-adrenergicreceptor(βAR)internalization.UsingPI(3)Kmutantswitheitherproteinorlipidphosphorylationactivity,weidentifythecytoskeletalproteinnon-muscletropomyosinasasubstrateofPI(3)K,whichisphospho-