Multiple translational isoforms give functional specificity to serum- and glucocorticoid-induced kinase 1
Multiple translational isoforms give functional specificity to serum- and glucocorticoid-induced kinase 1
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DOI：
10.1091/mbc.e06-10-0968
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发表时间：
2007-06-01
影响因子：
3.3
通讯作者：
Canessa, Cecilia M.
中科院分区：
文献类型：
--
作者：
Arteaga, Maria Francisca;de la Rosa, Diego Alvarez;Canessa, Cecilia M.
血清和糖皮质激素诱导的激酶1是一种普遍存在的激酶，调节不同的过程，如离子转运和细胞存活。我们报告说，一个单一的SGK 1 mRNA产生不同的N-末端由于替代翻译起始亚型。长亚型，49和47 kDa，是最丰富的，定位于ER膜，表现出快速周转，其表达被ER应激降低，激活上皮钠通道（ENaC），并将FoxO 3a转录因子从细胞核转运到细胞质。短亚型，45和42 kDa，定位于细胞质和细胞核，表现出长半衰期和磷酸化糖原合成酶激酶-3 β。这些数据表明，在不同的细胞区室中激活Sgk 1是为Sgk 1信号通路提供功能特异性的关键。我们的结论是，不同的属性和功能专业化的Sgk 1的N-末端赋予功能的多样性，同时保持相同的核心激酶结构域。
Serum- and glucocorticoid-induced kinase 1 is a ubiquitous kinase that regulates diverse processes such as ion transport and cell survival. We report that a single SGK1 mRNA produces isoforms with different N-termini owing to alternative translation initiation. The long isoforms, 49 and 47 kDa, are the most abundant, localize to the ER membrane, exhibit rapid turnover, their expression is decreased by ER stress, activate the epithelial sodium channel (ENaC) and translocate FoxO3a transcriptional factors from the nucleus to the cytoplasm. The short isoforms, 45 and 42 kDa, localize to the cytoplasm and nucleus, exhibit long half-life and phosphorylate glycogen synthase kinase-3 ss. The data indicate that activation of Sgk1 in different cellular compartments is key to providing functional specificity to Sgk1 signaling pathways. We conclude that the distinct properties and functional specialization of Sgk1 given by the N-terminus confer versatility of function while maintaining the same core kinase domain.