Mitogen-activated protein kinase-dependent and -independent routes control shedding of transmembrane growth factors through multiple secretases.
[EN]Solubilization of a number of membrane proteins occurs by the action of cell-surface proteases, termed secretases. Recently, the activity of these secretases has been reported to be controlled by the extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2) and the p38 mitogen-activated protein...
| Autores: | , , , , |
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| Tipo de recurso: | artículo |
| Estado: | Versión publicada |
| Fecha de publicación: | 2002 |
| País: | España |
| Institución: | Universidad de Salamanca (USAL) |
| Repositorio: | GREDOS. Repositorio Institucional de la Universidad de Salamanca |
| OAI Identifier: | oai:gredos.usal.es:10366/167903 |
| Acceso en línea: | http://hdl.handle.net/10366/167903 |
| Access Level: | acceso abierto |
| Palabra clave: | Cleavage Growth factors MAPKs Secretases Neuregulin-1 Cell Line Cricetinae Metalloendopeptidases Cell Membrane Growth Substances Tetradecanoylphorbol Acetate Sorbitol Mitogen-Activated Protein Kinase 3 Protein Kinase C p38 Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase 1 Protein Precursors Ultraviolet Rays CHO Cells Mice Amyloid Precursor Protein Secretases Aspartic Acid Endopeptidases Mitogen-Activated Protein Kinases Solubility Rats Animals Protease Inhibitors ADAM Proteins Endopeptidases Transforming Growth Factor alpha 2302 Bioquímica proteína cinasa C ratones línea celular proteína cinasa activada por mitógenos 1 acetato de tetradecanoilforbol células CHO proteína cinasa activada por mitógenos 3 precursores de proteínas inhibidores de proteasas neurregulina-1 secretasas de la proteína precursora del amiloide sorbitol ácido aspártico endopeptidasas proteína cinasas activadas por mitógenos metaloendopeptidasas proteínas ADAM factor de crecimiento transformador alfa animales sustancias del crecimiento membrana celular solubilidad ratas proteína cinasas p38 activadas por mitógenos endopeptidasas rayos ultravioleta |
| Sumario: | [EN]Solubilization of a number of membrane proteins occurs by the action of cell-surface proteases, termed secretases. Recently, the activity of these secretases has been reported to be controlled by the extracellular signal-regulated kinases 1 and 2 (ERK1/ERK2) and the p38 mitogen-activated protein kinase (MAPK) routes. In the present paper, we show that shedding of membrane-anchored growth factors (MAGFs) may also occur through MAPK-independent routes. In Chinese-hamster ovary cells, cleavage induced by protein kinase C (PKC) stimulation was largely insensitive to inhibitors of the ERK1/ERK2 and p38 routes. Other reagents such as sorbitol or UV light stimulated MAGF cleavage independent of PKC. The action of sorbitol on cleavage was only partially prevented by the combined action of inhibitors of the p38 and ERK1/ERK2 routes, indicating that sorbitol can also stimulate shedding by MAPK-dependent and -independent routes. Studies in cells devoid of activity of the secretase tumour necrosis factor-alpha-converting enzyme (TACE) indicated that this protease had an essential role in PKC- and ERK1/ERK2-mediated shedding. However, secretases other than TACE may also cleave MAGFs since sorbitol could still induce shedding in these cells. These observations suggest that cleavage of MAGFs is a complex process in which multiple secretases, activated through different MAPK-dependent and -independent routes, are involved. |
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