2003
DOI: 10.1124/mi.3.3.157
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Na+-K+-ATPase-Mediated Signal Transduction: From Protein Interaction to Cellular Function

Abstract: The Na+-K+--ATPase, or Na+ pump, is a member of the P-type ATPase superfamily. In addition to pumping ions, Na+-K+--ATPase is engaged in assembly of multiple protein complexes that transmit signals to different intracellular compartments. The signaling function of the enzyme appears to have been acquired through the evolutionary incorporation of many specific binding motifs that interact with proteins and ligands. In some cell types the signaling Na+ --ATPase and its protein partners are compartmentalized in c… Show more

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Cited by 369 publications
(342 citation statements)
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“…Second, activation of several of these pathways is independent of changes in intracellular ion concentrations (Liu et al, 2000;Aydemir-Koksoy et al, 2001;Miyakawa-Naito et al, 2003). Third, Na/K-ATPase is found to interact directly with neighboring membrane proteins and organized cytosolic cascades of signaling complexes to transmit the ouabain signal to different intracellular compartments (Xie and Cai, 2003). Specifically, we have shown recently that the Na/K-ATPase is concentrated in caveolae together with its signaling partners and that binding of ouabain to the caveolar Na/K-ATPase activated the Na/K-ATPase signaling complex, resulting in tyrosine phosphorylation of multiple proteins including epidermal growth factor receptor (EGFR; Wang et al, 2004).…”
Section: Introductionmentioning
confidence: 99%
“…Second, activation of several of these pathways is independent of changes in intracellular ion concentrations (Liu et al, 2000;Aydemir-Koksoy et al, 2001;Miyakawa-Naito et al, 2003). Third, Na/K-ATPase is found to interact directly with neighboring membrane proteins and organized cytosolic cascades of signaling complexes to transmit the ouabain signal to different intracellular compartments (Xie and Cai, 2003). Specifically, we have shown recently that the Na/K-ATPase is concentrated in caveolae together with its signaling partners and that binding of ouabain to the caveolar Na/K-ATPase activated the Na/K-ATPase signaling complex, resulting in tyrosine phosphorylation of multiple proteins including epidermal growth factor receptor (EGFR; Wang et al, 2004).…”
Section: Introductionmentioning
confidence: 99%
“…In the past few years, it has become apparent that binding of either endogenous or exogenous cardiotonic steroids, such as ouabain, to caveolar Na + ,K + -ATPase evokes protein and lipid kinase cascades, thus generating several secondary messengers (22). This signaling pathway involves the association of protein tyrosine kinases (Src) with the Na + ,K + -ATPase in a caveolar domain (34).…”
Section: Acute Effects Of Picomole Quantities Of Ouabain On Vascular mentioning
confidence: 99%
“…As a result, downstream effectors are activated, resulting in the activation of protein kinase cascades and the generation of second messengers. This leads to a cascade that involves the generation of reactive oxygen species (ROS), activation of extracellular signal-regulated protein kinase (ERK) through activation of its mitogen-activated protein kinase (MEK), activation of phosphatidylinositol 3-kinase (PI3K), stimulation of endocytosis and activation of Akt, as well as activation of protein kinase C (22,34,35). This binding of ouabain to Na + ,K + -ATPase affects multiple cellular functions, thereby influencing cell growth, heart hypertrophy and apoptosis (22).…”
Section: Acute Effects Of Picomole Quantities Of Ouabain On Vascular mentioning
confidence: 99%
“…It can also drive secondary active co-/countertransporters, which are coupled to the gradient of extracellular to intracellular Na + concentration, such as the sodium glucose cotransporter and the Na + /Ca 2+ exchanger [23] . In addition, recent findings have suggested additional signaling modes of action of Na + /K + -ATPase [24][25][26] , implicating its regulation of several important cellular processes and highlighting potential therapeutic roles of its inhibitors (such as cardiac glycosides) in various diseases.…”
Section: Introductionmentioning
confidence: 99%