Cloning and characterization of a putative human serine/threonine protein kinase transcriptionally modified during anisotonic and isotonic alterations of cell volume

Abstract

Hepatic metabolism and gene expression are among other regulatory mechanisms controlled by the cellular hydration state, which changes rapidly in response to anisotonicity, concentrative substrate uptake, oxidative stress, and under the inf luence of hormones such as insulin and glucagon. Differential screening for cell volume sensitive transcripts in a human hepatoma cell line revealed a gene for a putative serine͞threonine kinase, h-sgk, which has 98% sequence identity to a serum-and glucocorticoid regulated kinase, sgk, cloned from a rat mammary tumor cell line. h-sgk transcript levels were strongly altered during anisotonic and isotonic cell volume changes. Within 30 min h-sgk RNA was, independent of de novo protein synthesis, induced upon cell shrinkage and, due to a complete stop in h-sgk transcription, reduced upon cell swelling. Comparable changes of sgk transcript levels were observed in a renal epithelial cell line. h-sgk mRNA was detected in all human tissues tested, with the highest levels in pancreas, liver, and heart. The putative serine͞threonine protein kinase h-sgk may provide a functional link between the cellular hydration state and metabolic control.

A brain-specific SGK1 splice isoform regulates expression of ASIC1 in neurons

“…It was originally identified as a glucocorticoid (1) and cell-volume-responsive gene (2). The most extensively studied target of SGK1 is the epithelial sodium channel, ENaC, which plays a crucial role in the regulation of body sodium (3).…”

BMK1 Mediates Growth Factor-induced Cell Proliferation through Direct Cellular Activation of Serum and Glucocorticoid-inducible Kinase

“…SGK is a serine/threonine protein kinase with significant sequence homology throughout its catalytic domain with protein kinase B, ribosomal protein S6 kinase, cAMP-dependent protein kinase, and members of the protein kinase C family (12). A variety of stimuli, including glucocorticoids, hydrogen peroxide, hyperosmotic stress, serum, and insulin-like growth factor, have been shown to induce both the cellular expression and kinase activity of SGK (12)(13)(14)(15)(16). Similar to BMK1, the activity of SGK is closely linked to the G 1 /S transition of the cell cycle (17).…”

Anisoosmotic regulation of the Nopp140 mRNA in H4IIE rat hepatoma cells and primary hepatocytes

“…Furthermore, an osmosensitive transcriptional regulation of h-sgk, a serum-and glucocorticoid-regulated serine/ threonine protein kinase, was identi¢ed [14]. Recently, osmosensitive mRNA expression of Mi-2 autoantigen, a member of the SNF/RAD 54 helicase family, was shown in H4IIE hepatoma cells and rat primary hepatocytes [15].…”