Sweadner K J, Feschenko M S
Laboratory of Membrane Biology, Neuroscience Center, Massachusetts General Hospital, Charlestown, MA 02129, USA.
Am J Physiol Cell Physiol. 2001 Apr;280(4):C1017-26. doi: 10.1152/ajpcell.2001.280.4.C1017.
Regulation of Na-K-ATPase by cAMP-dependent protein kinase occurs in a variety of tissues. Phosphorylation of the enzyme's catalytic subunit at a classical phosphorylation consensus motif has been observed with purified enzyme. Demonstration of phosphorylation at the same site in normal living cells or tissues has been more difficult, however, making it uncertain that the Na-K-ATPase is a direct physiological substrate of the kinase. Recently, the structure of the homologous sarco(endo)plasmic reticulum Ca-ATPase (SERCA1a) has been determined at 2.6 A resolution (Toyoshima C, Nakasako M, Nomura H, and Ogawa H. Nature 405: 647-655, 2000.), and the Na-K- ATPase should have the same fold. Here, the Na-K-ATPase sequence has been aligned with the Ca-ATPase structure to examine the predicted disposition of the phosphorylation site. The location is close to the membrane and partially buried by adjacent loops, and the site is unlikely to be accessible to the kinase in this conformation. Conditions that may expose the site or further bury it are discussed to highlight the issues facing future research on regulation of Na-K-ATPase by cAMP-dependent pathways.
环磷酸腺苷（cAMP）依赖性蛋白激酶对钠钾ATP酶的调节作用存在于多种组织中。在纯化的酶中，已观察到该酶催化亚基在一个典型的磷酸化共有基序处发生磷酸化。然而，要在正常活细胞或组织中的同一部位证明磷酸化则更为困难，这使得钠钾ATP酶是否是该激酶的直接生理底物尚不确定。最近，已确定同源的肌浆网/内质网钙ATP酶（SERCA1a）的结构分辨率为2.6埃（丰岛C、中迫M、野村H和小川H。《自然》405: 647 - 655，2000年），钠钾ATP酶应该具有相同的折叠结构。在此，已将钠钾ATP酶序列与钙ATP酶结构进行比对，以检查磷酸化位点的预测位置。该位置靠近膜且部分被相邻环掩埋，在这种构象下该位点不太可能被激酶接近。文中讨论了可能使该位点暴露或进一步掩埋的条件，以突出未来关于cAMP依赖性途径对钠钾ATP酶调节研究面临的问题。
