Activation of extracellular signal-regulated protein kinase 5 downregulates FasL upon osmotic stress
| Autor: | Xin Wang, Katherine A. Hinchliffe, Raymond P. Boot-Handford, Andrew C Robinson, R Khosravi-Far, Lynnette Knowles, Cathy Tournier, Katherine G. Finegan |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Fas Ligand Protein
Down-Regulation Apoptosis Mice Transgenic MAP Kinase Kinase 5 Mitogen-activated protein kinase kinase MAP2K7 Mice Osmotic Pressure Animals Sorbitol ASK1 c-Raf Molecular Biology Cells Cultured Mitogen-Activated Protein Kinase 7 biology MAP kinase kinase kinase Cyclin-dependent kinase 4 Akt/PKB signaling pathway Forkhead Box Protein O3 Cyclin-dependent kinase 2 Forkhead Transcription Factors Receptor Cross-Talk Cell Biology Fibroblasts Molecular biology Cell biology biology.protein Proto-Oncogene Proteins c-akt Gene Deletion Signal Transduction |
| Zdroj: | Cell Death & Differentiation. 13:2099-2108 |
| ISSN: | 1476-5403 1350-9047 |
| Popis: | Extracellular signal-regulated protein kinase (ERK) 5 is a mitogen-activated protein kinase (MAPK) that is activated by dual phosphorylation via a unique MAPK/ERK kinase 5, MEK5. The physiological importance of this signaling cascade is underscored by the early embryonic death caused by the targeted deletion of the erk5 or the mek5 genes in mice. Here, we have found that ERK5 is required for mediating the survival of fibroblasts under basal conditions and in response to sorbitol treatment. Increased Fas ligand (FasL) expression acts as a positive feedback loop to enhance apoptosis of ERK5- or MEK5-deficient cells under conditions of osmotic stress. Compared to wild-type cells, erk5-/- and mek5-/- fibroblasts treated with sorbitol display a reduced protein kinase B (PKB) activity associated with increased Forkhead box O3a (Foxo3a) activity. Based on these results, we conclude that the ERK5 signaling pathway promotes cell survival by downregulating FasL expression via a mechanism that implicates PKB-dependent inhibition of Foxo3a downstream of phosphoinositide 3 kinase. |
| Databáze: | OpenAIRE |
| Externí odkaz: |
|