The c-Jun NH 2 -terminal kinase is essential for epidermal growth factor expression during epidermal morphogenesis
| Autor: | Anthony Wong, Richard A. Flavell, Mary E.P. Goad, Claire R. Weston, J. Perry Hall, Roger J. Davis |
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| Rok vydání: | 2004 |
| Předmět: |
MAP Kinase Signaling System
Morphogenesis Biology Proinflammatory cytokine Mice Tongue Epidermal growth factor medicine Animals RNA Messenger Receptor Lung In Situ Hybridization Skin Multidisciplinary Epidermal Growth Factor Epidermis (botany) Kinase JNK Mitogen-Activated Protein Kinases Neural tube Eyelids Gene Expression Regulation Developmental Biological Sciences Immunohistochemistry Molecular biology Cell biology Intestines Isoenzymes Mice Inbred C57BL medicine.anatomical_structure Signal transduction Oligonucleotide Probes |
| Zdroj: | Proceedings of the National Academy of Sciences. 101:14114-14119 |
| ISSN: | 1091-6490 0027-8424 |
| DOI: | 10.1073/pnas.0406061101 |
| Popis: | The c-Jun NH 2 -terminal kinase (JNK) group of mitogen-activated protein kinases is activated in response to a wide array of cellular stresses and proinflammatory cytokines. Roles for JNK in the developing nervous system and T-cell-mediated immunity have been established by detailed studies of mice with compound mutations in the Jnk genes. However, little is known concerning the roles of JNK in other mammalian tissues. Mice lacking both of the ubiquitously expressed isoforms (JNK1 and -2) die during midgestation with neural tube closure defects and brain abnormalities. Here we show that JNK-deficient mice exhibit delayed epithelial development in the epidermis, intestines, and lungs. In addition, JNK-deficient mice exhibit an eyelid closure defect associated with markedly reduced epidermal growth factor (EGF) receptor function, and loss of expression of the ligand EGF. We further demonstrate that adult mice lacking either JNK1 or -2 display striking differences in epidermal proliferation and differentiation, indicative of distinct roles for these kinases in the skin. We conclude that JNK is necessary for epithelial morphogenesis and is an essential regulator of signal transduction by the EGF receptor in the epidermis. |
| Databáze: | OpenAIRE |
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