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 Se 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 mu M epidermal growth factor doubled the activity of p42 mitogen-activated protein kinase without activating glycogen synthase.