Proapoptotic Function of the MET Tyrosine Kinase Receptor through Caspase Cleavage

Autor: Julien Deheuninck, Véronique Fafeur, Anice Moumen, Catherine Leroy, Fabienne Lamballe, Zongling Ji, Emilie Puchois, Filipe Calheiros Lourenço, David Tulasne, Flavio Maina, Patrick Mehlen
Přispěvatelé: Institut de Biologie du Développement de Marseille (IBDM), Aix Marseille Université (AMU)-Centre National de la Recherche Scientifique (CNRS)
Rok vydání: 2004
Předmět:
Cell Survival
Blotting
Western
Molecular Sequence Data
Apoptosis
[SDV.BC]Life Sciences [q-bio]/Cellular Biology
Ligands
Transfection
Cleavage (embryo)
Receptor tyrosine kinase
Mice
03 medical and health sciences
Dogs
0302 clinical medicine
In Situ Nick-End Labeling
Animals
Amino Acid Sequence
Enzyme Inhibitors
Tyrosine
Cell Growth and Development
Molecular Biology
Cells
Cultured
Caspase
030304 developmental biology
Neurons
Aspartic Acid
0303 health sciences
Dose-Response Relationship
Drug
biology
Caspase 3
Cell Biology
Proto-Oncogene Proteins c-met
Molecular biology
Recombinant Proteins
Protein Structure
Tertiary
Cell biology
Microscopy
Fluorescence
Protein kinase domain
Acetylation
Caspases
Protein Biosynthesis
030220 oncology & carcinogenesis
Hepatocytes
biology.protein
Cytokines
Tyrosine kinase
Plasmids
Zdroj: Molecular and Cellular Biology
Molecular and Cellular Biology, 2004, 24, pp.10328-10339
Molecular and Cellular Biology, American Society for Microbiology, 2004, 24, pp.10328-10339
ISSN: 1098-5549
0270-7306
DOI: 10.1128/mcb.24.23.10328-10339.2004
Popis: The MET tyrosine kinase, the receptor of hepatocyte growth factor-scatter factor (HGF/SF), is known to be essential for normal development and cell survival. We report that stress stimuli induce the caspase-mediated cleavage of MET in physiological cellular targets, such as epithelial cells, embryonic hepatocytes, and cortical neurons. Cleavage occurs at aspartic residue 1000 within the SVD site of the juxtamembrane region, independently of the crucial docking tyrosine residues Y1001 or Y1347 and Y1354. This cleavage generates an intracellular 40-kDa MET fragment containing the kinase domain. The p40 MET fragment itself causes apoptosis of MDCK epithelial cells and embryonic cortical neurons, whereas its kinase-dead version is impaired in proapoptotic activity. Finally, HGF/SF treatment does not favor MET cleavage and apoptosis, confirming the known survival role of ligand-activated MET. Our results show that stress stimuli convert the MET survival receptor into a proapoptotic factor.
Databáze: OpenAIRE
Externí odkaz: