WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter in HeLa cells
WNK1 and OSR1 regulate the Na+, K+, 2Cl- cotransporter in HeLa cells
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DOI：
10.1073/pnas.0604607103
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发表时间：
2006-07-18
影响因子：
11.1
通讯作者：
Cobb, Melanie H.
中科院分区：
文献类型：
--
作者：
Anselmo, Anthony N.;Earnest, Svetlana;Cobb, Melanie H.
氧化应激反应激酶（OSR）1和不育20相关的富含脯氨酸和丙氨酸的激酶（SPAK）是与钠、钾、二氯共转运蛋白NKCC结合的Ste20 p相关的蛋白激酶。在这里，我们提出的证据表明，没有赖氨酸[K]（WNK）1调节OSR 1，SPAK和NKCC活动的蛋白激酶。OSR 1在细胞中与WNK 1复合存在，在体外被重组WNK 1激活，并在细胞中以WNK 1依赖性方式磷酸化。通过使用小干扰RNA从HeLa细胞中消耗WNK 1降低OSR 1激酶活性。此外，WNK 1或OSR 1的缺失降低了NKCC活性，表明WNK 1和OSR 1都是NKCC功能所需的。OSR 1和SPAK可能是WNK 1和NKCC之间的联系，有助于哺乳动物的容量调节和血压稳态。
Oxidative stress-responsive kinase (OSR) 1 and sterile20-related, proline-, alanine-rich kinase (SPAK) are Ste20p-related protein kinases that bind to the sodium, potassium, two chloride cotransporter, NKCC. Here we present evidence that the protein kinase with no lysine [K] (WNK) 1 regulates OSR1, SPAK, and NKCC activities. OSR1 exists in a complex with WNK1 in cells, is activated by recombinant WNK1 in vitro, and is phosphorylated in a WNK1-dependent manner in cells. Depletion of WNK1 from HeLa cells by using small interfering RNA reduces OSR1 kinase activity. In addition, depletion of either WNK1 or OSR1 reduces NKCC activity, indicating that WNK1 and OSR1 are both required for NKCC function. OSR1 and SPAK are likely links between WNK1 and NKCC in a pathway that contributes to volume regulation and blood pressure homeostasis in mammals.