Kahle Kristopher T, Rinehart Jesse, Giebisch Gerhard, Gamba Gerardo, Hebert Steven C, Lifton Richard P
Department of Neurosurgery, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
Trends Endocrinol Metab. 2008 Apr;19(3):91-5. doi: 10.1016/j.tem.2008.01.001. Epub 2008 Feb 14.
The discovery that mutations in WNK4 [encoding a member of the WNK family - so named because of the unique substitution of cysteine for lysine at a nearly invariant residue within subdomain II of its catalytic core: with no K (lysine)] cause pseudohypoaldosteronism type II, an autosomal dominant form of human hypertension, provided the initial clue that this serine/threonine kinase is a crucial part of a complex renal salt regulatory system. Recent findings from physiological studies of WNK4 in Xenopus laevis oocytes, mammalian cell systems and in vivo in mouse models have provided novel insights into the mechanisms by which the kidney regulates salt homeostasis, and therefore blood pressure, downstream of aldosterone signaling in mammals. The current evidence supports a model in which WNK4 coordinates the activities of diverse aldosterone-sensitive mediators of ion transport in the distal nephron to promote normal homeostasis in response to physiological perturbation.
WNK4（编码WNK家族的一个成员，因其催化核心亚结构域II内一个几乎不变的残基上赖氨酸被半胱氨酸独特取代而得名：无K（赖氨酸））中的突变会导致II型假性醛固酮增多症，这是一种常染色体显性形式的人类高血压，这一发现提供了最初线索，表明这种丝氨酸/苏氨酸激酶是复杂的肾脏盐调节系统的关键组成部分。最近在非洲爪蟾卵母细胞、哺乳动物细胞系统以及小鼠模型体内对WNK4进行的生理学研究结果，为哺乳动物醛固酮信号下游肾脏调节盐稳态进而调节血压的机制提供了新见解。目前的证据支持一种模型，即WNK4协调远曲小管中多种醛固酮敏感的离子转运介质的活性，以促进对生理扰动作出反应的正常稳态。
