Editing Sodium–potassium pump (section)

=== Functioning as signal transducer ===
Within the last decade{{when|date=February 2018}}, many independent labs have demonstrated that, in addition to the classical ion transporting, this membrane protein can also relay extracellular [[ouabain]]-binding signalling into the cell through regulation of [[protein tyrosine phosphorylation]]. For instance, a study investigated the function of {{chem2|Na+/K+}}-ATPase in foot muscle and hepatopancreas in land snail ''Otala lactea'' by comparing the active and estivating states.<ref name= Ramnanan >{{cite journal |vauthors=Ramnanan CJ, Storey KB |date=February 2006 |title=Suppression of Na<sup>+</sup>/K<sup>+</sup>-ATPase activity during estivation in the land snail ''Otala lactea'' |journal=The Journal of Experimental Biology |volume=209 |issue=Pt 4 |pages=677–88 |doi=10.1242/jeb.02052 |pmid=16449562 |doi-access=free |s2cid=39271006}}</ref> They concluded that reversible phosphorylation can control the same means of coordinating ATP use by this ion pump with the rates of the ATP generation by catabolic pathways in estivating ''O. lactea''. The downstream signals through ouabain-triggered protein phosphorylation events include activation of the [[mitogen-activated protein kinase]] (MAPK) signal cascades, mitochondrial [[reactive oxygen species]] (ROS) production, as well as activation of [[phospholipase C]] (PLC) and [[inositol triphosphate]] (IP3) receptor ([[IP3R]]) in different intracellular compartments.<ref>{{cite journal | vauthors = Yuan Z, Cai T, Tian J, Ivanov AV, Giovannucci DR, Xie Z | title = Na/K-ATPase tethers phospholipase C and IP3 receptor into a calcium-regulatory complex | journal = Molecular Biology of the Cell | volume = 16 | issue = 9 | pages = 4034–45 | date = September 2005 | pmid = 15975899 | pmc = 1196317 | doi = 10.1091/mbc.E05-04-0295 }}</ref>

Protein-protein interactions play a very important role in {{chem2|Na+}}-{{chem2|K+}} pump-mediated signal transduction. For example, the {{chem2|Na+}}-{{chem2|K+}} pump interacts directly with [[Src (gene)|Src]], a [[non-receptor tyrosine kinase]], to form a signaling receptor complex.<ref>{{cite journal | vauthors = Tian J, Cai T, Yuan Z, Wang H, Liu L, Haas M, Maksimova E, Huang XY, Xie ZJ | display-authors = 6 | title = Binding of Src to Na<sup>+</sup>/K<sup>+</sup>-ATPase forms a functional signaling complex | journal = Molecular Biology of the Cell | volume = 17 | issue = 1 | pages = 317–26 | date = January 2006 | pmid = 16267270 | pmc = 1345669 | doi = 10.1091/mbc.E05-08-0735 }}</ref> Src is initially inhibited by the {{chem2|Na+}}-{{chem2|K+}} pump. However, upon subsequent ouabain binding, the Src kinase domain is released and then activated. Based on this scenario, NaKtide, a peptide Src inhibitor derived from the {{chem2|Na+}}-{{chem2|K+}} pump, was developed as a functional ouabain–{{chem2|Na+}}-{{chem2|K+}} pump-mediated signal transduction.<ref>{{cite journal | vauthors = Li Z, Cai T, Tian J, Xie JX, Zhao X, Liu L, Shapiro JI, Xie Z | display-authors = 6 | title = NaKtide, a Na/K-ATPase-derived peptide Src inhibitor, antagonizes ouabain-activated signal transduction in cultured cells | journal = The Journal of Biological Chemistry | volume = 284 | issue = 31 | pages = 21066–76 | date = July 2009 | pmid = 19506077 | pmc = 2742871 | doi = 10.1074/jbc.M109.013821 | doi-access = free }}</ref> {{chem2|Na+}}-{{chem2|K+}} pump also interacts with [[ankyrin]], [[IP3R]], [[PI3K]], [[PLCgamma1]] and [[cofilin]].<ref>{{cite journal | vauthors = Lee K, Jung J, Kim M, Guidotti G | title = Interaction of the alpha subunit of Na,K-ATPase with cofilin | journal = The Biochemical Journal | volume = 353 | issue = Pt 2 | pages = 377–85 | date = January 2001 | pmid = 11139403 | pmc = 1221581 | doi = 10.1042/0264-6021:3530377 }}</ref>