title: Identification of a potential receptor that couples ion transport to protein kinase activity.
abstract: In our previous studies, we have demonstrated that the Src-coupled α1 Na/K-ATPase works as a receptor for cardiotonic steroids, such as ouabain, to regulate cellular protein kinase cascades. Here, we explore further the structural determinants of the interaction between the α1 Na/K-ATPase and Src and demonstrate that the Src-coupled α1 Na/K-ATPase allows the cell to decode the transmembrane transport activity of the Na/K-ATPase to turn on/off protein kinases. The α1 Na/K-ATPase undergoes E1/E2 conformational transition during an ion pumping cycle. The amount of E1 and E2 Na/K-ATPase is regulated by extracellular K(+) and intracellular Na(+). Using purified enzyme preparations we find that the E1 Na/K-ATPase can bind both the Src SH2 and kinase domains simultaneously and keep Src in an inactive state. Conversely, the E1 to E2 transition releases the kinase domain and activates the associated Src. Moreover, we demonstrate that changes in E1/E2 Na/K-ATPase by either Na(+) or K(+) are capable of regulating Src and Src effectors in live cells. Together, the data suggest that the Src-coupled α1 Na/K-ATPase may act as a Na(+)/K(+) receptor, allowing salt to regulate cellular function through Src and Src effectors.
authors.affiliation: Department of Physiology, University of Toledo College of Medicine, Toledo, Ohio 43614, USA.
authors.forename: Qiqi
authors.initials: Q
authors.lastname: Ye
authors.forename: Zhichuan
authors.initials: Z
authors.lastname: Li
authors.forename: Jiang
authors.initials: J
authors.lastname: Tian
authors.forename: Jeffrey X
authors.initials: JX
authors.lastname: Xie
authors.forename: Lijun
authors.initials: L
authors.lastname: Liu
authors.forename: Zijian
authors.initials: Z
authors.lastname: Xie
mesh_terms: D002460:Cell Line; D004789:Enzyme Activation; D006801:Humans; D017136:Ion Transport / Q000502:physiology; D011188:Potassium / Q000378:metabolism*; D017434:Protein Structure, Tertiary; D012964:Sodium / Q000378:metabolism*; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics / Q000378:metabolism*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
chemical_list: D012964:Sodium; D019061:src-Family Kinases; D000254:Sodium-Potassium-Exchanging ATPase; D011188:Potassium