PMID- 15542841 OWN - NLM STAT- MEDLINE DCOM- 20050104 LR - 20181113 IS - 0270-7306 (Print) IS - 1098-5549 (Electronic) IS - 0270-7306 (Linking) VI - 24 IP - 23 DP - 2004 Dec TI - Proapoptotic function of the MET tyrosine kinase receptor through caspase cleavage. PG - 10328-39 AB - 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. FAU - Tulasne, David AU - Tulasne D AD - CNRS UMR 8117, Institut de Biologie de Lille, Institut Pasteur de Lille, B.P. 447, 59021 Lille, France. david.tulasne@ibl.fr FAU - Deheuninck, Julien AU - Deheuninck J FAU - Lourenco, Filipe Calheiros AU - Lourenco FC FAU - Lamballe, Fabienne AU - Lamballe F FAU - Ji, Zongling AU - Ji Z FAU - Leroy, Catherine AU - Leroy C FAU - Puchois, Emilie AU - Puchois E FAU - Moumen, Anice AU - Moumen A FAU - Maina, Flavio AU - Maina F FAU - Mehlen, Patrick AU - Mehlen P FAU - Fafeur, Veronique AU - Fafeur V LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Mol Cell Biol JT - Molecular and cellular biology JID - 8109087 RN - 0 (Cytokines) RN - 0 (Enzyme Inhibitors) RN - 0 (Ligands) RN - 0 (Recombinant Proteins) RN - 30KYC7MIAI (Aspartic Acid) RN - 42HK56048U (Tyrosine) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 3.4.22.- (Casp3 protein, mouse) RN - EC 3.4.22.- (Caspase 3) RN - EC 3.4.22.- (Caspases) SB - IM MH - Amino Acid Sequence MH - Animals MH - *Apoptosis MH - Aspartic Acid/chemistry/metabolism MH - Blotting, Western MH - Caspase 3 MH - Caspases/*metabolism MH - Cell Survival MH - Cells, Cultured MH - Cytokines/metabolism MH - Dogs MH - Dose-Response Relationship, Drug MH - Enzyme Inhibitors/pharmacology MH - Hepatocytes/metabolism MH - In Situ Nick-End Labeling MH - Ligands MH - Mice MH - Microscopy, Fluorescence MH - Molecular Sequence Data MH - Neurons/metabolism MH - Plasmids/metabolism MH - Protein Biosynthesis MH - Protein Structure, Tertiary MH - Proto-Oncogene Proteins c-met/metabolism/*physiology MH - Recombinant Proteins/chemistry MH - Transfection MH - Tyrosine/chemistry PMC - PMC529022 EDAT- 2004/11/16 09:00 MHDA- 2005/01/05 09:00 PMCR- 2004/12/01 CRDT- 2004/11/16 09:00 PHST- 2004/11/16 09:00 [pubmed] PHST- 2005/01/05 09:00 [medline] PHST- 2004/11/16 09:00 [entrez] PHST- 2004/12/01 00:00 [pmc-release] AID - 24/23/10328 [pii] AID - 0531-04 [pii] AID - 10.1128/MCB.24.23.10328-10339.2004 [doi] PST - ppublish SO - Mol Cell Biol. 2004 Dec;24(23):10328-39. doi: 10.1128/MCB.24.23.10328-10339.2004.