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• W2094291218 abstract "Background. Following hypoosmotic stress-induced cell volume change, the actin cytoskeleton reorganizes itself. The role of this reorganization in the activation of the phosphatidylinositol 3-OH-kinase/protein kinase B/activator protein 1 (PI-3-K/PKB/AP-1) proliferative signaling cascade is unknown. Focal adhesion kinase (FAK) participates in the cytoskeleton-based activation of PI-3-K. We hypothesized that hypoosmotic stress-induced activation of PKB and AP-1 in HepG2 cells is dependent on an intact actin cytoskeleton and subsequent FAK phosphorylation. Methods. HepG2 cells were incubated for 1 h with or without 20 μM cytochalasin D, an actin disrupter, and were then exposed for up to 30 min to hypoosmotic medium (200 mOsm/L) to induce swelling. Tumor necrosis factor α (1.4 nM) and medium alone served as positive and negative controls, respectively. Western blots measured cytoplasmic phosphorylated or total FAK and PKB. EMSAs measured nuclear AP-1. All experiments were performed in triplicate. Results. Exposure to hypoosmotic stress resulted in activation of the following signaling messengers in a sequential fashion: (1) phosphorylation of FAK occurred by 2 min, (2) phosphorylation of PKB occurred by 10 min, (3) nuclear translocation of AP-1 occurred by 30 min. All three signaling events were abolished when these cells were pretreated with cytochalasin D. Conclusion. Actin reorganization following hypoosmotic stress is essential for the FAK-mediated activation of the PI-3-K/PKB/AP-1 proliferative cascade. These data delineate a possible mechanism by which the cell swelling-induced cytoskeletal changes can initiate proliferative signal transduction in human liver cancer." @default.
• W2094291218 created "2016-06-24" @default.
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• W2094291218 date "2001-10-01" @default.
• W2094291218 modified "2023-10-03" @default.
• W2094291218 title "Activator Protein 1 Activation following Hypoosmotic Stress in HepG2 Cells Is Actin Cytoskeleton Dependent" @default.
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• W2094291218 doi "https://doi.org/10.1006/jsre.2001.6225" @default.
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