Abstract
The Serum- and Glucocorticoid-induced Kinase 1, SGK1, exhibits a broad range of cellular functions that include regulation of the number of ion channels in plasma membrane and modulation of signaling pathways of cell survival. This diversity of functions is made possible by various regulatory processes acting upon the SGK1 gene, giving rise to various isoforms: SGK1_v1–5, each with distinct properties and distinct aminotermini that serve to target proteins to different subcellular compartments. Among cellular effects of SGK1 expression is to indirectly modulate gene transcription by phosphorylating transcriptional factors of the FOXO family. Here we examined if SGK1.1 (SGK1_v2; NM_001143676), which associates primarily to the plasma membrane, is also able to regulate gene expression. Using a differential gene expression approach we identified six genes upregulated by SGK1.1 in HeLa cells. Further analysis of transcript and protein levels validated two genes: BCL2-associated athanogene 4 (BAG-4) and Brox. The results indicate that SGK1.1 regulates gene transcription upon a different set of genes some of which participate in cell survival pathways (BAG-4) and others in intracellular vesicular traffic (Brox).
Highlights
The human and mouse genomes contain three independent genes coding for closely related protein families known as SGK1, SGK2, and SGK3 [1,2]
We examined the differential gene expression induced in HeLa cells [27] by the constitutively active form SGK1.1S515D vs. the inactive form SGK1.1K220A
A subtraction was performed in order to generate a library enriched in cDNAs activated by SGK1.1
Summary
The human and mouse genomes contain three independent genes coding for closely related protein families known as SGK1, SGK2, and SGK3 [1,2]. Participation of SGK1 in such a broad spectrum of cellular functions is made possible by a multilayer system of regulation that includes regulation of gene transcription by different promoters, differential splicing of transcripts that generates various isoforms (SGK1_v1–5), phosphorylation of the kinase domain that increases enzymatic activity, and specific subcellular localization of isoforms within cells [17,18,19,20,21,22]. SGK1.1 (SGK1_v2; NM_001143676) is a splice isoform conserved from rodent to humans and highly expressed in the nervous system [23,24] The aminoterminus of the SGK1.1 isoform contains a cluster of large hydrophobic and positively charged residues that together form a motif that binds PtdIns(4,5)P2 thereby sending SGK1.1 to the plasma membrane in resting cells [23]. We examined the differential gene expression induced in HeLa cells [27] by the constitutively active form SGK1.1S515D vs. the inactive form SGK1.1K220A
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