Aperia Anita, Brismar Hjalmar, Uhlén Per
Science for Life Laboratory, Dept of Women's and Children's Health, Karolinska Institutet, Sweden.
Science for Life Laboratory, Dept of Women's and Children's Health, Karolinska Institutet, Sweden; Science for Life Laboratory, Dept of Applied Physics, KTH Royal Institute of Technology, Sweden.
Cell Calcium. 2020 Apr 26;88:102210. doi: 10.1016/j.ceca.2020.102210.
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.
钠钾ATP酶是一种普遍存在的多功能蛋白质，它既作为离子泵，又作为信号转导器发挥作用。其信号功能可被无毒浓度的哇巴因激活。在上皮细胞中，与哇巴因结合的钠钾ATP酶通过一个短的线性基序与肌醇1,4,5 -三磷酸受体相连，以激活低频钙离子振荡。在几分钟内，这种由哇巴因介导的信号导致了2580个磷酸化位点的磷酸化或去磷酸化。控制细胞增殖和细胞黏附的蛋白质以及钙调蛋白调节的蛋白质在哇巴因磷酸化调节的蛋白质中富集。肌醇1,4,5 -三磷酸受体和基质相互作用分子对于钙离子振荡的启动都是必不可少的，它们属于哇巴因磷酸化调节的蛋白质。哇巴因诱发的上皮细胞钙离子信号的下游效应包括干扰内在的线粒体凋亡过程以及刺激胚胎生长过程。钠钾ATP酶作为离子泵和信号转导器的双重功能现已得到充分证实，评估这一普遍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。
