h-sgk serine-threonine protein kinase as transcriptional target of p38/MAPkinase pathway in HepG2 human hepatoma cells

The human serum and glucocorticoid dependent serine/ threonine kinase h-sgk has previously been discovered as cell volume regulated gene. The present study has been performed to elucidate the involvement of p38-kinase in the transcriptional control of h-sgk by osmotic cell shrinkage. The p38-kinase has previously been cloned as the mammalian homologue of HOG1 kinase, which constitutes a part of the osmosensor in the yeast Saccharomyces cerevisiae . Phosphorylated (active) p38-kinase has been estimated with Western blotti ng, transcription of hsgk using Northern blotting. Both, increase of extrac ellular NaCl concentration by 50 mmol/ I and addition of 10 mu mol/l anisom ycin increase phosphorylation of the p38-kinase within 5 to 10 minutes. hsg k transcription is upregulated by addition of 50 mmol/ I NaCl and by anisom ycin (10 mu mol/l), effects completely inhibited by the specific p38-kinase inhibitor, SE 203580 (10 mu mol/l). In conclusion, the stimulation of h-sg k transcription by osmotic cell shrinkage is mediated by p38-kinase. Copyri ght (C) 2000 S. Karger AG, Basel.