Serum- and glucocorticoid-dependent kinase, cell volume, and the regulation of epithelial transport

• Published in: Comparative Biochemistry and Physiology, Part A Vol. 130; no. 3; pp. 367 - 376
• Main Authors: Fillon, S, Wärntges, S, Matskevitch, J, Moschen, I, Setiawan, I, Gamper, N, Feng, Y.X, Stegen, C, Friedrich, B, Waldegger, S, Bröer, S, Wagner, C.A, Huber, S.M, Klingel, K, Vereninov, A, Lang, F
• Format: Book Review Journal Article
• Language: English
• Published: United States Elsevier Inc 01.10.2001
• Subjects: Animals; Biological Transport; Cell Size; Cell volume regulation; Epithelial Na + channel; Epithelium - metabolism; Immediate-Early Proteins; Intestine; Intracellular Ca 2+ activity; Kidney; Na +/K +/2Cl −-cotransporter; Nuclear Proteins; Pancreas; Protein-Serine-Threonine Kinases - metabolism; sgk; Intracellular Ca 2+ activity; Na +/K +/2Cl −-cotransporter; Intestine; sgk; Epithelial Na + channel; Cell volume regulation; Pancreas; Kidney
• ISSN: 1095-6433; 1531-4332
• DOI: 10.1016/S1095-6433(01)00422-6

Ample pharmacological evidence points to a role of kinases in the regulation of cell volume. Given the limited selectivity of most inhibitors, however, the specific molecules involved have remained largely elusive. The search for cell volume regulated genes in liver HepG2 cells led to the discovery of the human serum- and glucocorticoid-dependent serine/threonine kinase hsgk1. Transcription and expression of hsgk1 is markedly and rapidly upregulated by osmotic and isotonic cell shrinkage. The effect of osmotic cell shrinkage on hsgk1 is mediated by p38 kinase. Further stimuli of hsgk1 transcription include glucocorticoids, aldosterone, TGF-β1, serum, increase of intracellular Ca 2+ and phorbolesters, whereas cAMP downregulates hsgk1 transcription. The hsgk1 protein is expressed in several epithelial tissues including human pancreas, intestine, kidney, and shark rectal gland. Co-expression of hsgk1 with the renal epithelial Na +-channel ENaC or the Na +/K +/2Cl −-cotransporter NKCC2 (BSC1) in Xenopus oocytes, accelerates insertion of the transport proteins into the cell membrane and thus, stimulates channel or transport activity. Thus, hsgk1 participates in the regulation of transport by steroids and secretagogues increasing intracellular Ca 2+-activity. The stimulation of hsgk1 transcription by TGF-β1 may further bear pathophysiological relevance.