Post-translational modifications of na+/K+-atpase subunits: regulatory mechanisms and functional implications

Abstract

The Na+/K+-ATPase (NKA), commonly referred to as the sodium pump, is a ubiquitous membrane protein that maintains cellular homeostasis by expelling three sodium ions from the cell and importing two potassium ions using ATP hydrolysis. This enzyme is critical for maintaining resting membrane potential, generating action potentials, and facilitating substance absorption and gland secretion. Additionally, NKA plays a significant role in overall homeostasis and has been implicated in tumor cell regulation. This review aims to provide a comprehensive overview of the post-translational modifications (PTMs) that modulate the function, stability, and intracellular localization of NKA. These PTMs, including phosphorylation, glycosylation, palmitoylation, ubiquitination, and glutathionylation, have emerged as key regulators of NKA activity. By exploring these modifications, we seek to uncover novel insights into the dynamic regulation of NKA and its role in various physiological processes and disease states. Recent research has unveiled the intricate interplay between different PTMs of NKA, highlighting their independent and synergistic effects on enzyme function. These modifications not only influence NKA’s ion transport capabilities but also interact with other regulatory pathways, thereby playing a crucial role in health and disease. This review will delve into the specific types of PTMs identified on NKA subunits, their functional consequences, and the potential for these modifications to serve as therapeutic targets. By synthesizing current knowledge and identifying gaps in understanding, this review aims to advance the field and inspire future research directions.