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Mending Fences: Na,K-ATPase signaling via Ca2+ in the maintenance of epithelium integrity.
Cell Calcium ( IF 4.3 ) Pub Date : 2020-04-26 , DOI: 10.1016/j.ceca.2020.102210
Anita Aperia 1 , Hjalmar Brismar 2 , Per Uhlén 3
Affiliation  

Na,K-ATPase is a ubiquitous multifunctional protein that acts both as an ion pump and as a signal transducer. The signaling function is activated by ouabain in non-toxic concentrations. In epithelial cells the ouabain-bound Na,K-ATPase connects with the inositol 1,4,5-trisphosphate receptor via a short linear motif to activate low frequency Ca2+ oscillations. Within a couple of minutes this ouabain mediated signal has resulted in phosphorylation or dephosphorylation of 2580 phospho-sites. Proteins that control cell proliferation and cell adhesion and calmodulin regulated proteins are enriched among the ouabain phosphor-regulated proteins. The inositol 1,4,5-trisphosphate receptor and the stromal interaction molecule, which are both essential for the initiation of Ca2+ oscillations, belong to the ouabain phosphor-regulated proteins. Downstream effects of the ouabain-evoked Ca2+ signal in epithelial cells include interference with the intrinsic mitochondrial apoptotic process and stimulation of embryonic growth processes. The dual function of Na,K-ATPase as an ion pump and a signal transducer is now well established and evaluation of the physiological and pathophysiological consequences of this universal signal emerges as an urgent topic for future studies.

中文翻译:


修补栅栏:Na,K-ATPase 信号通过 Ca2+ 维持上皮完整性。



Na,K-ATP 酶是一种普遍存在的多功能蛋白质,既充当离子泵又充当信号转导器。哇巴因在无毒浓度下可激活信号传导功能。在上皮细胞中,哇巴因结合的 Na,K-ATP 酶通过短线性基序与肌醇 1,4,5-三磷酸受体连接,以激活低频 Ca2+ 振荡。几分钟内,哇巴因介导的信号导致 2580 个磷酸位点磷酸化或去磷酸化。哇巴因磷调节蛋白中富含控制细胞增殖和细胞粘附的蛋白以及钙调蛋白调节蛋白。肌醇 1,4,5-三磷酸受体和基质相互作用分子对于 Ca2+ 振荡的启动都是必需的,属于哇巴因磷调节蛋白。上皮细胞中哇巴因诱发的 Ca2+ 信号的下游影响包括干扰内在的线粒体凋亡过程和刺激胚胎生长过程。 Na,K-ATP酶作为离子泵和信号转导器的双重功能现已得到很好的确立,评估这种通用信号的生理和病理生理后果成为未来研究的一个紧迫课题。
更新日期:2020-04-26
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