Role of serum and glucocorticoid-regulated protein kinase (SGK) on insulin signaling pathway

1.SGK1相互作用蛋白的鉴定为了筛选与SGK1相互作用的蛋白(S)，利用人脑文库进行了双杂交筛选。鉴定了具有两个PDZ结构域和磷酸酪氨酸结合结构域的接头蛋白Mint2。SGK1与存在于C端的PDZ结构域相互作用，但不与N端PDZ结构域和PBD相互作用。用SGK1.2的激活剂之一过氧化氢处理细胞后，SGK1和Mint2蛋白的相互作用增强。SGK亚型参与K+通道的调节SGK1最初被认为是糖皮质激素敏感基因。随后，SGK1被证明激活包括K+通道在内的离子通道。最近，两个同源的激酶SGK2和SGK3被克隆出来。目的：阐明SGK亚型在K+通道调节中的作用，以及这些亚型表达对肾上皮细胞电特性的影响。转染SGK1、SGK2或SGK3使电压门控性K+电流增加，表明三种SGK亚型对K+通道均有较强的刺激作用。

1. Identification of SGK1 interacting proteinIn order to identify protein(s) which interact with SGK1, two hybrid screen was carried out using human brain cDNA library. Adaptor protein Mint2 which possesses two PDZ domains and phosphotyrosine binding domain (PBD) was identified. SGK1 interacted with PDZ domain which exists at C-terminal but not with N-terminal PDZ domain and PBD. The interaction of SGK1 and Mint2 proteins was increased by treatment of cells with hydrogen peroxide, one of the activator of SGK1.2. Involvement of SGK isoforms in regulation of K+ channelsSGK1 was originally identified as a glucocoticoid sensitive gene. Subsequently SGK1 was shown to activate ion channels including K+ channel. Recently two homologous kinases, SGK2 and SGK3 have been cloned. To elucidate the role of SGK isoforms on regulation of K+ channel, effect of expression of these isoforms on electrical properties of renal epithelial cells. Transfection of SGK1, SGK2 or SGK3 increased the voltage-gated K+ current indicating strong stimulating effect of all three isoforms of SGK on K.+ channels.