Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated shedding.
[EN]The ectodomain of certain transmembrane proteins can be released by the action of cell surface proteases, termed secretases. Here we have investigated how mitogen-activated protein kinases (MAPKs) control the shedding of membrane proteins. We show that extracellular signal-regulated kinase (Erk)...
| 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:10366/167830 |
| Acceso en línea: | http://hdl.handle.net/10366/167830 |
| Access Level: | acceso abierto |
| Palabra clave: | TACE, Cleavage, MAPKs Retroviridae Binding Sites Transfection Restriction Mapping Humans HeLa Cells Metalloendopeptidases Amino Acid Sequence Carrier Proteins Membrane Proteins Mitogen-Activated Protein Kinases Tetradecanoylphorbol Acetate Phosphorylation Threonine Protein Kinase C ADAM Proteins 2302 Biochemistry proteína cinasa C mapeo por restricción humanos treonina proteínas transportadoras células HeLa proteína cinasas activadas por mitógenos acetato de tetradecanoilforbol sitios de unión transfección metaloendopeptidasas proteínas ADAM secuencia de aminoácidos proteínas de membranas fosforilación |
| Sumario: | [EN]The ectodomain of certain transmembrane proteins can be released by the action of cell surface proteases, termed secretases. Here we have investigated how mitogen-activated protein kinases (MAPKs) control the shedding of membrane proteins. We show that extracellular signal-regulated kinase (Erk) acts as an intermediate in protein kinase C-regulated TrkA cleavage. We report that the cytosolic tail of the tumor necrosis factor alpha-converting enzyme (TACE) is phosphorylated by Erk at threonine 735. In addition, we show that Erk and TACE associate. This association is favored by Erk activation and by the presence of threonine 735. In contrast to the Erk route, the p38 MAPK was able to stimulate TrkA cleavage in cells devoid of TACE activity, indicating that other proteases are also involved in TrkA shedding. These results demonstrate that secretases are able to discriminate between the different stimuli that trigger membrane protein ectodomain cleavage and indicate that phosphorylation by MAPKs may regulate the proteolytic function of membrane secretases. |
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