Comparison of WNK4 and WNK1 kinase and inhibiting activities.
Comparison of WNK4 and WNK1 kinase and inhibiting activities.
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WNK4 和 WNK1 激酶及抑制活性的比较。
DOI：
10.1016/j.bbrc.2004.03.132
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发表时间：
2004
影响因子：
3.1
通讯作者：
Ellison,DavidH
中科院分区：
文献类型：
--
作者：
Wang,Zhaohong;Yang,Chao-Ling;Ellison,DavidH
WNK激酶是一种新型的丝氨酸/苏氨酸蛋白激酶。WNK家族的两个成员WNK 1和WNK 4的突变导致家族性高钾血症性高血压。这些激酶调节跨不同上皮细胞的离子转运; WNK 4通过减少它们在质膜上的出现来降低Na-Cl协同转运蛋白活性和钾通道ROMK的活性。我们在体外检测了WNK 1和WNK 4的激酶活性。谷胱甘肽S-转移酶（GST）融合蛋白的WNK 1激酶结构域磷酸化本身和底物蛋白，如前所述。一个更长的结构，含有自抑制结构域，没有。GST WNK 4激酶结构域构建体在体外或HEK 293细胞中显示无激酶活性。包含与WNK 1的自抑制结构域同源的区域的WNK 4构建体抑制WNK 1激酶活性。短WNK 4区段WNK 4（444-518）的抑制大于WNK 4（444-563）的抑制。总之，这些结果表明，WNK 4必须被目前未知的因素激活才能表现出激酶活性，并且WNK 4含有可以抑制WNK 1激酶活性的抑制结构域。
WNK kinases are novel serine/threonine protein kinases. Mutations in two members of the WNK family, WNK1 and WNK4, cause familial hyperkalemic hypertension. These kinases regulate ion transport across diverse epithelia; WNK4 reduces activity of the Na–Cl cotransporter activity and the potassium channel, ROMK, by reducing their appearance at the plasma membrane. We examined the kinase activity of WNK1 and WNK4 in vitro. A glutathione S-transferase (GST) fusion protein of the WNK1 kinse domain phosphorylated itself and a substrate protein, as reported previously. A longer construct, containing the autoinhibitory domain, did not. A GST WNK4 kinase domain construct demonstrated no kinase activity, in vitro or in HEK 293 cells. WNK4 constructs that included a region homologous to the autoinhibitory domain of WNK1 inhibited WNK1 kinase activity. Inhibition by a short WNK4 segment, WNK4 (444–518), was greater than inhibition by WNK4 (444–563). Together, these results suggest that WNK4 must be activated by currently unknown factors to exhibit kinase activity and that WNK4 contains an inhibitory domain that can inhibit the kinase activity of WNK1.
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DOI：
10.1016/s0021-9258(19)37575-1
发表时间：
1988-10
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
A. Hershko
通讯作者：
A. Hershko
人类泛素载体蛋白E2(Mr = 17,000)与酵母DNA修复基因RAD6同源。
影响因子：
11.4
作者：
R. Schneider;C. Eckerskorn;F. Lottspeich;M. Schweiger
通讯作者：
M. Schweiger
DOI：
10.1073/pnas.87.7.2695
发表时间：
1990-04
影响因子：
11.1
作者：
P. Sung;S. Prakash;L. Prakash
通讯作者：
P. Sung;S. Prakash;L. Prakash
DOI：
10.1002/j.1460-2075.1990.tb08258.x
发表时间：
1990-05
期刊：
The EMBO Journal
影响因子：
--
作者：
P. Reynolds;Marcel H.M. Koken;Jan H. J. Hoeijmakers;S. Prakash;L. Prakash
通讯作者：
P. Reynolds;Marcel H.M. Koken;Jan H. J. Hoeijmakers;S. Prakash;L. Prakash
影响因子：
10.5
作者：
Patrick Sung;S. Prakash;L. Prakash
通讯作者：
Patrick Sung;S. Prakash;L. Prakash