Protein kinase signaling pathway triggered by cell swelling and involved in the activation of glycogen synthase and acetyl-CoA carboxylase in isolated rat hepatocytes.
Incubation of isolated hepatocytes with glutamine or proline or in hypotonic media is known to activate glycogen synthase and acetyl-CoA carboxylase as a result of cell swelling. We report here that the same experimental conditions caused an activation of phosphatidylinositol 3-kinase and p70 ribosomal protein S6 kinase (p70 S6 kinase) but did not modify the activity of p42 mitogen-activated protein kinase. In addition, rapamycin, an inhibitor of p70 S6 kinase activation, prevented the amino acid- and hypotonicity-induced activation of p70 S6 kinase but did not block the activation of glycogen synthase and acetyl-CoA carboxylase, thus ruling out p70 S6 kinase as a necessary component in the activation pathway. By contrast, wortmannin or LY294002, inhibitors of phosphatidylinositol 3-kinase, completely blocked the activation of phosphatidylinositol 3-kinase and p70 S6 kinase and partly blocked the activation of glycogen synthase and acetyl-CoA carboxylase. Therefore, phosphatidylinositol 3-kinase might be a component of the signaling pathway that is triggered by cell swelling and is responsible, at least in part, for the activation of glycogen synthase and acetyl-CoA carboxylase. Incubation of hepatocytes with 0.1 microM epidermal growth factor doubled the activity of p42 mitogen-activated protein kinase without activating glycogen synthase.
Krause
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Hormone and Metabolic Research Unit, University of Louvain Medical School, and International Institute of Cellular and Molecular Pathology, B-1200 Brussels, Belgium.
Rider
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MH
Hue
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D000103:Acetyl-CoA Carboxylase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000494:pharmacology; D000730:Androstadienes / Q000494:pharmacology; D000818:Animals; D048429:Cell Size; D004789:Enzyme Activation; D004791:Enzyme Inhibitors; D006006:Glycogen Synthase / Q000037:antagonists & inhibitors / Q000378:metabolism*; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology / Q000201:enzymology*; D008297:Male; D008969:Molecular Sequence Data; D009994:Osmolar Concentration; D011090:Polyenes / Q000494:pharmacology; D011494:Protein Kinases / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D015398:Signal Transduction; D020123:Sirolimus; D000077191:Wortmannin
D000596:Amino Acids; D000730:Androstadienes; D004791:Enzyme Inhibitors; D011090:Polyenes; D006006:Glycogen Synthase; D011494:Protein Kinases; D000103:Acetyl-CoA Carboxylase; D020123:Sirolimus; D000077191:Wortmannin