Role of SGK2 in Sodium Transport in the Kidney

SGK2 在肾脏钠转运中的作用

• 批准号: 6917822
• 负责人: ALAN C PAO
• 金额: $ 5.49万
• 依托单位: UNIVERSITY OF CALIFORNIA, SAN FRANCISCO
• 依托单位国家: 美国
• 财政年份: 2004
• 资助国家: 美国
• 起止时间: 2004-03-01 至 2006-02-28
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/6917822
• 关键词: Xenopus oocyte; adrenalectomy; aldosterone; biological transport; dexamethasone; enzyme activity; gene expression; hormone regulation /control mechanism; immunocytochemistry; in situ hybridization; laboratory rat; northern blottings; phosphatidylinositol 3 kinase; phosphotransferases; postdoctoral investigator; protein localization; renal tubule; sodium ion; tissue /cell culture; transfection

DESCRIPTION (provided by applicant): The overall goal of this research proposal is to understand the expression, regulation, and function of serum and glucocorticoid induced kinase 2 (sgk2) and the precise role it plays in sodium (Na+) transport across the nephron. The molecular basis underlying aldosterone-induced Na+ transport in the nephron has not been fully elucidated. Recently, sgk1 has been identified as a central mediator between early aldosterone effects and epithelial Na+ channel-mediated Na+ transport. Even more recently, two additional isoforms of sgk, sgk2 and sgk3, have been discovered. Localization of sgk2 expression and assessment of hormone-mediated sgk2 regulation will be performed through aldosterone and dexamethasone infusion in rats with subsequent sgk2 expression analyses by in situ hybridization and immunocytochemistry. Identification of downstream effectors of sgk2 will be performed through co-expression assays of Xenopus laevis oocytes with sgk2 and nephron segment-specific Na+ co-transporters. Finally, a tetracycline-inducible (Tet-On) sgk2 expression system in A6 cells will be constructed to isolate the specific effects of sgk2 on Na+ transport in a time-dependent manner. Given that inappropriate Na+ handling can result in extracellular fluid volume expansion and hypertension in humans, understanding the signaling pathways mediating aldosterone-induced Na+ transport in the kidney is clinically important.

描述（由申请人提供）：本研究计划的总体目标是了解血清和糖皮质激素诱导的激酶 2 (sgk2) 的表达、调节和功能，以及它在钠 (Na+) 跨肾单位转运中发挥的精确作用。醛固酮诱导肾单位 Na+ 转运的分子基础尚未完全阐明。最近，sgk1 已被确定为早期醛固酮效应和上皮 Na+ 通道介导的 Na+ 转运之间的中心介质。最近，还发现了 sgk 的另外两种亚型：sgk2 和 sgk3。将通过向大鼠输注醛固酮和地塞米松来定位 sgk2 表达并评估激素介导的 sgk2 调节，随后通过原位杂交和免疫细胞化学进行 sgk2 表达分析。 sgk2 下游效应子的鉴定将通过非洲爪蟾卵母细胞与 sgk2 和肾单位片段特异性 Na+ 共转运蛋白的共表达测定来进行。最后，将在A6细胞中构建四环素诱导（Tet-On）sgk2表达系统，以分离sgk2以时间依赖性方式对Na+转运的特定影响。鉴于不恰当的 Na+ 处理可能导致人类细胞外液体积膨胀和高血压，了解介导醛固酮诱导的肾脏中 Na+ 转运的信号通路具有重要的临床意义。

项目成果

Serum- and glucocorticoid-inducible kinase SGK2 regulates human organic anion transporters 4 via ubiquitin ligase Nedd4-2.

血清和糖皮质激素诱导激酶 SGK2 通过泛素连接酶 Nedd4-2 调节人有机阴离子转运蛋白 4。

• DOI: 10.1016/j.bcp.2015.11.024
• 发表时间: 2016-02-15
• 期刊: Biochemical pharmacology
• 影响因子: 5.8
• 作者: Wang, Haoxun;Xu, Da;Toh, May Fern;Pao, Alan C.;You, Guofeng
• 通讯作者: You, Guofeng