Abstract
The Na/K-ATPase (NKA), or Na pump, is a member of the P-type ATPase superfamily. In addition to pumping ions across cell membrane, it is engaged in assembly of multiple protein complexes in the plasma membrane. This assembly allows NKA to perform many non-pumping functions including signal transduction that are important for animal physiology and disease progression. This article will focus on the role of protein interaction in NKA-mediated signal transduction, and its potential utility as target for developing new therapeutics.
Highlights
The Na/K-ATPase (NKA) was discovered by Skou 60 years ago as the molecular machine for pumping Na+ and K+ across cell membrane [1]
We will give an in-depth discussion of NKA-mediated signal transduction; its role in animal physiology and disease progression; theoretical consideration and experimental evidence of direct protein interactions as the molecular mechanism; and the possibility of targeting such interactions for developing new therapeutics
The interaction between Src Src homology 2 (SH2) domain and NKA α1 is not reduced upon ouabain binding, it is important in the recruitment and targeting of Src
Summary
The Na/K-ATPase (NKA) was discovered by Skou 60 years ago as the molecular machine for pumping Na+ and K+ across cell membrane [1]. CTS could stimulate protein tyrosine phosphorylation and a number of growth-related pathways in cell type- and tissue type-dependent manner [53,54,55,56,57], which has been largely confirmed by studies from other laboratories around the world [49,58,59,60,61,62,63,64,65,66,67,68,69,70,71,72,73,74,75] These new findings suggest NKA as an important signal transducer, and the involvement of protein kinase cascades in the cell growth regulation by CTS rather than the inhibition of ATPase activity. These issues have driven the ten years of investigations, and led to our current appreciation of the molecular basis of NKA-mediated signal transduction in cells
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