The WNKs: atypical protein kinases with pleiotropic actions.
The WNKs: atypical protein kinases with pleiotropic actions.
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DOI：
10.1152/physrev.00017.2010
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发表时间：
2011-01
影响因子：
33.6
通讯作者：
Ellison DH
中科院分区：
文献类型：
--
作者：
McCormick JA;Ellison DH
wnk是丝氨酸/苏氨酸激酶，由kinome的一个独特分支组成。它们之所以如此命名，是因为它不寻常地放置了一种必需的催化赖氨酸。WNKs现已在多种生物中被发现。在人类和其他哺乳动物中，有四个基因编码WNKs。WNKs在信息水平上广泛表达，尽管关于蛋白质表达的数据更为有限。在WNK被发现后不久，编码WNK 1和4的基因突变被确定导致人类疾病，家族性高钾血症高血压（也称为假性低醛固酮增多症II，或戈登综合征）。因此，研究的一个主要焦点是分析WNK激酶在肾脏调节离子运输中的作用。最近，一种不同的WNK1突变被确定为遗传性感觉和自主神经病变II型（HSANII）的原因，HSANII是一种早发的常染色体外周感觉神经疾病。因此，WNKs代表了治疗人类疾病的一个重要的潜在靶点家族，进一步阐明它们在肾和脑外的生理作用是必要的。本文综述了WNKs的基因结构及调控其表达和活性的机制。随后，我们概述了WNKs的底物和靶点，以及WNKs对肾脏和其他部位细胞生理的影响。接下来，概述了这些影响对综合生理功能的影响。最后，我们讨论了已知的和推测的wnk的病理生理相关性。
WNKs are serine/threonine kinases that comprise a unique branch of the kinome. They are so-named owing to the unusual placement of an essential catalytic lysine. WNKs have now been identified in diverse organisms. In humans and other mammals, four genes encoding WNKs. WNKs are widely expressed at the message level, although data on protein expression is more limited. Soon after the WNKs were identified, mutations in genes encoding WNK 1 and 4 were determined to cause the human disease, Familial Hyperkalemic Hypertension (also known as pseudohypoaldosteronism II, or Gordon’s Syndrome). For this reason, a major focus of investigation has been to dissect the role of WNK kinases in renal regulation of ion transport. More recently, a different mutation in WNK1 was identified as the cause of hereditary sensory and autonomic neuropathy type II (HSANII), an early-onset autosomal disease of peripheral sensory nerves. Thus, the WNKs represent an important family of potential targets for the treatment of human disease, and further elucidation of their physiological actions outside of the kidney and brain is necessary. In this review, we describe the gene structure and mechanisms regulating expression and activity of the WNKs. Subsequently, we outline substrates and targets of WNKs, and effects of WNKs on cellular physiology, both in the kidney and elsewhere. Next, consequences of these effects on integrated physiological function are outlined. Finally, we discuss the known and putative pathophysiological relevance of the WNKs.
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影响因子：
19.6
作者：
Cai, H.;Cebotaru, V.;Guggino, W. B.
通讯作者：
Guggino, W. B.
DOI：
10.1152/ajprenal.00358.2009
发表时间：
2009-09-01
影响因子：
4.2
作者：
Ahlstrom, Robert;Yu, Alan S. L.
通讯作者：
Yu, Alan S. L.
影响因子：
--
作者：
BRAUTBAR, N;LEVI, J;KLEEMAN, CR
通讯作者：
KLEEMAN, CR
影响因子：
3.5
作者：
Abidi, F. E.;Miano, M. G.;Schwartz, C. E.
通讯作者：
Schwartz, C. E.
影响因子：
3.5
作者：
Benjafield, AV;Katyk, K;Morris, BJ
通讯作者：
Morris, BJ