Amplification of apoptosis through sequential caspase cleavage of the MET tyrosine kinase receptor
| Autor: | Véronique Fafeur, Frédéric Ancot, David Tulasne, Bénédicte Foveau, Catherine Leroy, Zongling Ji, Julien Deheuninck |
|---|---|
| Rok vydání: | 2006 |
| Předmět: |
Cell Survival
Apoptosis Cleavage (embryo) Receptor tyrosine kinase Cell Line Mice medicine Animals Humans Amino Acid Sequence Receptor Molecular Biology Caspase biology Hepatocyte Growth Factor Cell Biology Proto-Oncogene Proteins c-met Molecular biology Microscopy Fluorescence Acetylation Caspases biology.protein Hepatocyte growth factor medicine.drug |
| Zdroj: | Cell Death & Differentiation. 14:752-764 |
| ISSN: | 1476-5403 1350-9047 |
| DOI: | 10.1038/sj.cdd.4402080 |
| Popis: | Activation of the MET tyrosine kinase receptor by hepatocyte growth factor/scatter factor is classically associated with cell survival. Nonetheless, stress stimuli can lead to a caspase-dependent cleavage of MET within its juxtamembrane region, which generate a proapoptotic 40 kDa fragment (p40 MET). We report here that p40 MET is in fact generated through an additional caspase cleavage of MET within its extreme C-terminal region, which removes only few amino acids. We evidenced a hierarchical organization of these cleavages, with the C-terminal cleavage favoring the juxtamembrane one. As a functional consequence, the removal of the last amino acids of p40 MET increases its apoptotic capacity. Finally, cells expressing a MET receptor mutated at the C-terminal caspase site are unable to generate p40 MET and are resistant to apoptosis, indicating that generation of p40 MET amplifies apoptosis. These results revealed a two-step caspase cleavage of MET resulting in the reshaping of this survival receptor to a proapoptotic factor. |
| Databáze: | OpenAIRE |
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