蛋白激酶A和蛋白激酶C对肾脏Kir7.1钾通道的双重调节
Dual regulation of renal Kir7.1 potassium channels by protein Kinase A and protein Kinase C.
作者信息
Zhang Wei, Zitron Edgar, Bloehs Ramona, Müller-Krebs Sandra, Scholz Eberhard, Zeier Martin, Katus Hugo, Karle Christoph, Schwenger Vedat
机构信息
Department of Nephrology, Renal Center Heidelberg, Im Neuenheimer Feld 162, D-69120 Heidelberg, Germany.
出版信息
Biochem Biophys Res Commun. 2008 Dec 19;377(3):981-6. doi: 10.1016/j.bbrc.2008.10.110. Epub 2008 Oct 29.
The renal inward rectifier potassium channel Kir7.1 has been proposed to be functionally important for tubular K(+) recycling and secretion. This study investigated the regulation of Kir7.1 by PKA and PKC. Cloned human Kir7.1 channels were expressed heterologously in Xenopus oocytes. After pharmacological PKC activation, Kir7.1 currents were strongly inhibited. Co-application of PKC inhibitors attenuated this effect. Inactivation of PKC consensus sites also strongly attenuated the effect with a single site ((201)S) being essential for almost the total PKC sensitivity. In contrast, PKA activation induced an increase of Kir7.1 currents. This effect was absent in mutant Kir7.1 channels lacking PKA consensus site (287)S. In summary, this study demonstrates the dual regulation of Kir7.1 channel function by PKA and PKC. Structurally, these regulations depend on two key residues in the C-terminal channel domain ((Ser)201 for PKC and (Ser)287 for PKA).
肾内向整流钾通道Kir7.1被认为在肾小管钾离子循环和分泌中具有重要功能。本研究调查了蛋白激酶A（PKA）和蛋白激酶C（PKC）对Kir7.1的调节作用。克隆的人Kir7.1通道在非洲爪蟾卵母细胞中进行异源表达。经药理学方法激活PKC后，Kir7.1电流受到强烈抑制。联合应用PKC抑制剂可减弱这种效应。PKC共有序列位点的失活也强烈减弱了该效应，其中单个位点（(201)S）对几乎全部PKC敏感性至关重要。相反，PKA激活导致Kir7.1电流增加。在缺乏PKA共有序列位点(287)S的突变型Kir7.1通道中，这种效应不存在。总之，本研究证明了PKA和PKC对Kir7.1通道功能的双重调节作用。在结构上，这些调节作用依赖于通道C末端结构域中的两个关键残基（PKC作用的(Ser)201和PKA作用的(Ser)287）。
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