Effects of osmotic stress on the activity of MAPKs and PDGFR-beta-mediated signal transduction in NIH-3T3 fibroblasts
| Autor: | Maj-Britt Nielsen, Else K. Hoffmann, S. T. Christensen |
|---|---|
| Rok vydání: | 2008 |
| Předmět: |
biology
Osmotic shock Physiology Cell volume Cell migration Cell Biology Cell biology Receptor Platelet-Derived Growth Factor beta Mice Apoptosis Osmotic Pressure biology.protein NIH 3T3 Cells Osmotic pressure Animals Signal transduction Mitogen-Activated Protein Kinases Receptor Platelet-derived growth factor receptor Signal Transduction |
| Zdroj: | American journal of physiology. Cell physiology. 294(4) |
| ISSN: | 0363-6143 |
| Popis: | Signaling in cell proliferation, cell migration, and apoptosis is highly affected by osmotic stress and changes in cell volume, although the mechanisms underlying the significance of cell volume as a signal in cell growth and death are poorly understood. In this study, we used NIH-3T3 fibroblasts in a serum- and nutrient-free inorganic medium (300 mosM) to analyze the effects of osmotic stress on MAPK activity and PDGF receptor (PDGFR)-β-mediated signal transduction. We found that hypoosmolarity (cell swelling at 211 mosM) induced the phosphorylation and nuclear translocation of ERK1/2, most likely via a pathway independent of PDGFR-β and MEK1/2. Conversely, hyperosmolarity (cell shrinkage at 582 mosM) moved nuclear and phosphorylated ERK1/2 to the cytoplasm and induced the phosphorylation and nuclear translocation of p38 and phosphorylation of JNK1/2. In a series of parallel experiments, hypoosmolarity did not affect PDGF-BB-induced activation of PDGFR-β, whereas hyperosmolarity strongly inhibited ligand-dependent PDGFR-β activation as well as downstream mitogenic signal components of the receptor, including Akt and the MEK1/2-ERK1/2 pathway. Based on these results, we conclude that ligand-dependent activation of PDGFR-β and its downstream effectors Akt, MEK1/2, and ERK1/2 is strongly modulated (inhibited) by hyperosmotic cell shrinkage, whereas cell swelling does not seem to affect the activation of the receptor but rather to activate ERK1/2 via a different mechanism. It is thus likely that cell swelling via activation of ERK1/2 and cell shrinkage via activation of the p38 and JNK pathway and inhibition of the PDGFR signaling pathway may act as key players in the regulation of tissue homeostasis. |
| Databáze: | OpenAIRE |
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