Pflügers Archiv - European Journal of Physiology

, Volume 457, Issue 3, pp 635–644 | Cite as

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

Ion Channels


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.


Na/K-ATPase Tyrosine kinase Protein phosphorylation Receptor Protein kinase 


A domain

activation domain


autosomal dominant polycystic kidney disease


second cytosolic domain


third cytosolic domain


cardiotonic steroids


epidermal growth factor receptor


extracellular signal-regulated protein kinase


focal adhesion kinase


fluorescence resonance energy transfer




G protein-coupled receptor


inositol triphosphate


IP3 receptor


IP3R binding protein released with inositol 1,4,5-trisphosphate



N domain

nucleotide binding domain

P domain

phosphorylation domain


phosphatidylinositol 3-kinase


protein kinase C


phospholipase C


protein tyrosine kinases


renal outer medullary K channel


sarcoplasmic reticulum Ca-ATPase



We thank Ms. Martha Heck for editing the manuscript. This work was supported by NIH grants HL-36573 and HL-67963 awarded by the National Heart, Lung and Blood Institute and NIH grant GM-78565 awarded by the National Institute of General Medical Sciences.


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Copyright information

© Springer-Verlag 2008

Authors and Affiliations

  1. 1.Department of Physiology and PharmacologyUniversity of Toledo College of Medicine, Health Science CampusToledoUSA

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