WNK激酶的研究进展

Progress in WNK Kinases

WNK家族是近年来新发现的一类丝氨酸/苏氨酸蛋白激酶,因其激酶结构域第2亚单位上缺乏其他激酶所具有的用来结合ATP的赖氨酸残基而得名。哺乳动物的4种WNK激酶都由氨基端结构域,高度保守的丝氨酸/苏氨酸激酶结构域,自抑制结构域和至少两个螺旋-螺旋结构域组成。WNK1基因第一内含子的大片段缺失和WNK4螺旋-螺旋结构域一段高度保守区域的错义突变,可导致Gordon综合征,进一步研究发现WNK激酶能调节肾小管多种离子转运蛋白和离子通道,以维持电解质平衡。它不仅是遗传性高血压Gordon综合征的致病基因,而且可能参与原发性高血压的发病。此外,WNK激酶还与信号转导,细胞生长、凋亡和胚胎发育有关。

The WNK kinases are a small group of serine/threonine kinases found in recent years, without a catalytic lysine residue in subdomain Ⅱ which is necessary for other kinases to co-ordinate ATE All 4 members of WNK kinases in mammals contain a amino-terminal domain, a highly conserved serine/threonine ldnase domain, and at least 2 coiled-coil domains. Large deletions within the first intron in WNK1 or missense mutations in a highly conserved domain of coil-coiled domain of WNK4 can cause Gordon＇s syndrome. Further study discovered WNK kinases can regulate multiple transporters and ion channels on the renal tubular epithelial cell to maintain electrolyte balance. WNKs are not only disease-causing gene of the rare monogenic hypertension syndrome of Gordon＇s syndrome, but also candidate genes for essential hypertension. Furthermore, WNK kinases also affect signal conduction, cell growth and apoptosis and are essential for normal embryonic development.