The Na/K-ATPase (NKA) was discovered years ago as the molecular machine for pumping Na+ and K+ across cell membrane. NKA belongs to the P-type ATPase family.  Sodium potassium pump (Na(+)/K(+) ATPase) is a transmembrane protein complex found in all higher eukaryotes acting as a key energy-consuming pump maintaining ionic and osmotic balance in cells. Muscle cells had active transport mechanism allowing cells to move Na+ and K+ across cell membrane via the consumption of energy. ATPase is responsible for the active transport of three Na+ and two K+ across the plasma membrane in red blood cells. Ion pumping is linked to the cycle of conformational changes. Around the same time, cell biologists and renal physiologists developed a kidney NKA purification protocol, and generated a large number of important mechanistic and cell biological data that refine the structure, reaction mechanism, and cellular regulation of NKA. several NKA-interacting proteins are including ankyrin, adducin and FXYD family of proteins. 
FXYD1, also known as phospholemman (PLM), is a principal phosphorylation substrate of c-AMP dependent protein kinase A and of Ca2+-phospholipid-dependent protein kinase C at Ser68 (PKA), or at Ser63, Ser68 and Thr69(PKC). Unphosphorylated FXYD1 inhibits NKA through the direct protein interaction. In addition, a number of signaling proteins has also been identified during the studies of hormonal regulation of NKA trafficking in kidney epithelial cells. Dopamine stimulates the recruitment of arrestin, spinophilin, GPCR kinase and 14-3-3ε, to the α1 NKA. In another example, the association of 14-3-3ζ to the α1 subunit facilitates the binding of PI3K to the α1 subunit that subsequently leads to the endocytosis of the NKA. . Functionally, Bcl-2 proteins were also reported directly interacting with NKA. The interactions are critical for control of cell survival and apoptosis. The ratio of pro-survival and pro-apoptotic proteins interacting with NKA may determine NKA function. Binding of CTS to this NKA/Src receptor complex leads to the activation of the associated Src, recruitment of additional Src, and the initiation of the signal transduction processes.


1.Cui X, Xie Z. Molecules. 2017;22(6):990.