Mechanisms of aluminum fluoride- and insulin-stimulated p33 mRNA accumulation in rat hepatoma cells: involvement of a G protein and kinase action and demonstration of effects on mRNA turnover.
The insulin signalling pathway to control nuclear p33 gene expression was examined. An AlF4-stimulated pertussis toxin-insensitive G protein was shown to be involved. The action of AlF4- was completely blocked by deferoxamine. Insulin action was markedly stimulated in the presence of AlF4-. cAMP and diacylglycerol concentrations were examined as possible regulators but no increases were detected. The effects of AlF4- and of insulin were completely inhibited by the general kinase inhibitor H-7. A second calcium calmodulin protein kinase inhibitor, W-7, had no detectable effect. Insulin and AlF4- were shown to stabilize p33 mRNA.
Nagasaka
Y
Y
Department of Pharmacology, University of Virginia Health Sciences Center, Charlottesville 22908.
Okubo
M
M
Larner
J
J
D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000123:Acetyltransferases; D017607:Aluminum Compounds / Q000494:pharmacology; D000818:Animals; D000242:Cyclic AMP / Q000378:metabolism; D004075:Diglycerides / Q000378:metabolism; D005459:Fluorides / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006207:Half-Life; D007328:Insulin / Q000494:pharmacology; D007546:Isoquinolines / Q000494:pharmacology; D007700:Kinetics; D008114:Liver Neoplasms, Experimental / Q000235:genetics / Q000378:metabolism*; D037342:Pertussis Toxin; D010879:Piperazines / Q000494:pharmacology; D047428:Protein Kinase Inhibitors; D011494:Protein Kinases / Q000378:metabolism; D011506:Proteins / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism*; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D013449:Sulfonamides / Q000494:pharmacology; D010566:Virulence Factors, Bordetella / Q000494:pharmacology
D017607:Aluminum Compounds; D004075:Diglycerides; D007328:Insulin; D007546:Isoquinolines; D010879:Piperazines; D047428:Protein Kinase Inhibitors; D011506:Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D013449:Sulfonamides; D010566:Virulence Factors, Bordetella; C017967:W 7; D019307:1-(5-Isoquinolinesulfonyl)-2-Methylpiperazine; D000242:Cyclic AMP; D000123:Acetyltransferases; C077509:mim-1 protein, Gallus gallus; D037342:Pertussis Toxin; D011494:Protein Kinases; D019204:GTP-Binding Proteins; D005459:Fluorides; C032311:aluminum fluoride