Arteaga Maria Francisca, Alvarez de la Rosa Diego, Alvarez Jose A, Canessa Cecilia M
Department of Cellular and Molecular Physiology, Yale University, New Haven, CT 06510, USA.
Mol Biol Cell. 2007 Jun;18(6):2072-80. doi: 10.1091/mbc.e06-10-0968. Epub 2007 Mar 21.
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-3beta. 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.
血清和糖皮质激素诱导激酶1是一种普遍存在的激酶，可调节多种过程，如离子转运和细胞存活。我们报告称，由于可变翻译起始，单个SGK1 mRNA产生具有不同N端的异构体。49 kDa和47 kDa的长异构体最为丰富，定位于内质网（ER）膜，周转迅速，其表达受内质网应激抑制，可激活上皮钠通道（ENaC）并将FoxO3a转录因子从细胞核转运至细胞质。45 kDa和42 kDa的短异构体定位于细胞质和细胞核，半衰期长，并可磷酸化糖原合酶激酶-3β。数据表明，Sgk1在不同细胞区室中的激活是赋予Sgk1信号通路功能特异性的关键。我们得出结论，由N端赋予的Sgk1独特性质和功能特化在维持相同核心激酶结构域的同时赋予了功能多样性。
