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

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Abstract

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.

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Abbreviations

A domain:

activation domain

ADPKD:

autosomal dominant polycystic kidney disease

CD2:

second cytosolic domain

CD3:

third cytosolic domain

CTS:

cardiotonic steroids

EGFR:

epidermal growth factor receptor

ERK:

extracellular signal-regulated protein kinase

FAK:

focal adhesion kinase

FRET:

fluorescence resonance energy transfer

GST:

glutathione-S-transferase

GPCR:

G protein-coupled receptor

IP3:

inositol triphosphate

IP3R:

IP3 receptor

IRBIT:

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

MBG:

marinobufagenin

N domain:

nucleotide binding domain

P domain:

phosphorylation domain

PI3K:

phosphatidylinositol 3-kinase

PKC:

protein kinase C

PLC:

phospholipase C

PTKs:

protein tyrosine kinases

ROMK:

renal outer medullary K channel

SERCA:

sarcoplasmic reticulum Ca-ATPase

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Acknowledgments

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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  1. Department of Physiology and Pharmacology, University of Toledo College of Medicine, Health Science Campus, Mail Stop 1008, 3000 Arlington Avenue, Toledo, OH, 43614-2598, USA

    Zhichuan Li & Zijian Xie

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  1. Zhichuan Li
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  2. Zijian Xie
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Correspondence to Zijian Xie.

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Li, Z., Xie, Z. The Na/K-ATPase/Src complex and cardiotonic steroid-activated protein kinase cascades. Pflugers Arch - Eur J Physiol 457, 635–644 (2009). https://doi.org/10.1007/s00424-008-0470-0

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  • DOI: https://doi.org/10.1007/s00424-008-0470-0

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