A regulated NH2-terminal Sgk1 variant with enhanced function is expressed in the collecting duct.
A regulated NH2-terminal Sgk1 variant with enhanced function is expressed in the collecting duct.
复制标题
具有增强功能的受调节 NH2 末端 Sgk1 变体在集合管中表达。
DOI：
10.1152/ajprenal.00191.2012
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发表时间：
2012
期刊：
影响因子：
--
通讯作者：
Thomas,ChristieP
中科院分区：
文献类型：
--
作者：
Raikwar,NanditaS;Liu,KangZ;Thomas,ChristieP
SGK1是一种相对不稳定的激酶，调节肾脏远端肾单位上皮细胞的Na+转运。我们鉴定了人SGK1的5‘端变异交替转录本(SGK1_V3)，它表达于连接小管和集合管，受醛固酮和胰岛素的调节，并被预测编码NH2末端的SGK1异构体SGK1_i3。SGK1_i3在其NH2末端含有一个多碱基序KKR，调节HEK293细胞中表达蛋白的泛素化和稳定性。在Fisher大鼠甲状腺和mpkCCDC14细胞中，SGK1_i3对Na+转运的影响明显大于SGK1，其刺激作用依赖于激动域。SGK1_i3增加细胞表面裂解上皮Na+通道(ENaC)亚单位的丰度，这种作用受Nedd4-2共表达的抑制。这些数据表明，肾表达的SGK1亚型SGK1_i3具有更高的稳定性，受胰岛素和醛固酮的调节，当异源表达在集合管细胞中时，可以刺激ENaC的活性。
Sgk1 is a relatively unstable kinase that regulates epithelial Na+transport in the distal nephron of the kidney. We identified a 5′ variant alternate transcript of human Sgk1 (Sgk1_v3) that is expressed in the connecting tubule and collecting duct, is regulated by aldosterone and insulin, and is predicted to encode an NH2-terminal variant Sgk1 isoform, Sgk1_i3. Sgk1_i3 contains a polybasic motif, KKR, in its NH2terminus that regulates ubiquitination and stability of the expressed protein in HEK293 cells. In Fisher rat thyroid, and mpkCCDc14cells, Sgk1_i3 had a significantly greater effect on Na+transport compared with Sgk1 and its stimulatory effect was dependent on the kinase domain. Sgk1_i3 increased the abundance of cleaved epithelial Na+channel (ENaC) subunits at the cell surface, which was inhibited by coexpression of Nedd4–2. Together, the data demonstrate that a renally expressed Sgk1 isoform, Sgk1_i3, shows improved stability, is regulated by insulin and aldosterone, and stimulates ENaC activity when heterologously expressed in collecting duct cells.
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