h-sgk serine-threonine protein kinase as transcriptional target of p38/MAP kinase 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 blotting, transcription of hsgk using Northern blotting. Both, increase of extracellular NaCl concentration by 50 mmol/l and addition of 10 micromol/l anisomycin increase phosphorylation of the p38-kinase within 5 to 10 minutes. h-sgk transcription is upregulated by addition of 50 mmol/l NaCl and by anisomycin (10 micromol/l), effects completely inhibited by the specific p38-kinase inhibitor, SB 203580 (10 micromol/l). In conclusion, the stimulation of h-sgk transcription by osmotic cell shrinkage is mediated by p38-kinase.
Waldegger
S
S
Institut für Physiologie I, Gmelinstr. 5, D-72076 Tübingen, Germany.
Gabrysch
S
S
Barth
P
P
Fillon
S
S
Lang
F
F
D000841:Anisomycin / Q000494:pharmacology; D048429:Cell Size / Q000187:drug effects; D004789:Enzyme Activation / Q000187:drug effects; D015971:Gene Expression Regulation, Enzymologic / Q000187:drug effects; D006801:Humans; D007093:Imidazoles / Q000494:pharmacology; D017874:Immediate-Early Proteins; D020935:MAP Kinase Signaling System / Q000187:drug effects; D020928:Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*; D009687:Nuclear Proteins; D009997:Osmotic Pressure; D010766:Phosphorylation / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000235:genetics* / Q000378:metabolism; D011725:Pyridines / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012965:Sodium Chloride / Q000494:pharmacology; D014158:Transcription, Genetic / Q000187:drug effects / Q000235:genetics*; D014407:Tumor Cells, Cultured; D048051:p38 Mitogen-Activated Protein Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases
D000841:Anisomycin; D007093:Imidazoles; D017874:Immediate-Early Proteins; D020928:Mitogen-Activated Protein Kinases; D009687:Nuclear Proteins; D017346:Protein Serine-Threonine Kinases; D011725:Pyridines; D012333:RNA, Messenger; D012965:Sodium Chloride; D048051:p38 Mitogen-Activated Protein Kinases; D000099184:Serum-Glucocorticoid Regulated Kinases; C093642:SB 203580