Stress-activated protein kinases are negatively regulated by cell density
| Autor: | Serge Garbay, Curt M. Pfarr, Moshe Yaniv, François Traincard, Odile Jeannequin, Dominique Lallemand, Jonathan Ham, Latifa Bakiri |
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| Rok vydání: | 1998 |
| Předmět: |
MAPK/ERK pathway
Proto-Oncogene Proteins c-jun Ultraviolet Rays Cell Count Cell Cycle Proteins Biology p38 Mitogen-Activated Protein Kinases General Biochemistry Genetics and Molecular Biology Mice Cell Movement GTP-Binding Proteins Animals Phosphorylation Growth Substances cdc42 GTP-Binding Protein Protein kinase A Molecular Biology Cytoskeleton Confluency General Immunology and Microbiology Kinase General Neuroscience c-jun JNK Mitogen-Activated Protein Kinases Fibroblasts Actins rac GTP-Binding Proteins Cell biology Cdc42 GTP-Binding Protein Calcium-Calmodulin-Dependent Protein Kinases Mitogen-Activated Protein Kinases Signal transduction Protein Kinases Signal Transduction Research Article |
| Zdroj: | The EMBO Journal. 17:5615-5626 |
| ISSN: | 1460-2075 |
| DOI: | 10.1093/emboj/17.19.5615 |
| Popis: | Stimulation by UV irradiation, TNFalpha, as well as PDGF or EGF activates the JNK/SAPK signalling pathway in mouse fibroblasts. This results in the phosphorylation of the N-terminal domain of c-Jun, increasing its transactivation potency. Using an antibody that specifically recognizes c-Jun phosphorylated at Ser63, we show that culture confluency drastically inhibited c-Jun N-terminal phosphorylation due to the inhibition of the JNK/SAPK pathway. Transfection experiments demonstrate that the inhibition occurs at the same level as, or upstream of, the small G-proteins cdc42 and Rac1. In contrast, the classical MAPK pathway was insensitive to confluency. The inhibition of JNK/SAPK activation depended on the integrity of the actin microfilament network. These results were confirmed and extended in monolayer wounding experiments. After PDGF, EGF or UV stimulation, c-Jun was predominantly phosphorylated in cells bordering the wound, which are the cells that move to occupy the wounded area. Thus, modulation of the stress-dependent signal cascade by confluency will restrict c-Jun N-terminal phosphorylation in response to mitogenic or chemotactic agents to cells that border a wounded area. |
| Databáze: | OpenAIRE |
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