The Na/K-ATPase/Src complex and cardiotonic steroid-activated protein kinase cascades

The Na/K-ATPase was discovered by Skou in 1957. Since then, the efforts of numerous investigators have led to the following conclusions: (a) This enzyme is indeed the molecular machine for the ATP-dependent and -coupled transport of Na(+) and K(+) across the plasma membrane of a living cell in which such a process (sodium pump) is detected. (b) The Na/K-ATPase is also an important signal transducer that not only interacts and regulates protein kinases, but also functions as a scaffold, capable of bringing the affector and effectors together to form functional signalosomes. This minireview discusses the interaction between the Na/K-ATPase and Src to illustrate how a P-type ATPase can act as a receptor, converting a ligand-binding signal to the activation of protein kinase cascades and the generation of second messengers.