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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.

Titel:	Proapoptotic function of the MET tyrosine kinase receptor through caspase cleavage.
Autor/in / Beteiligte Person:	Tulasne, D ; Deheuninck, J ; Lourenco, FC ; Lamballe, F ; Ji, Z ; Leroy, C ; Puchois, E ; Moumen, A ; Maina, F ; Mehlen, P ; Fafeur, V
Link:	Full Text Finder (Volltext)
Zeitschrift:	Molecular and cellular biology, Jg. 24 (2004-12-01), Heft 23, S. 10328-39
Veröffentlichung:	2023- : [Philadelphia] : Taylor & Francis ; <i>Original Publication</i>: [Washington, D.C.] : American Society for Microbiology, [c1981-, 2004
Medientyp:	academicJournal
ISSN:	0270-7306 (print)
DOI:	10.1128/MCB.24.23.10328-10339.2004
Schlagwort:	Amino Acid Sequence Animals Aspartic Acid chemistry Aspartic Acid metabolism Blotting, Western Caspase 3 Cell Survival Cells, Cultured Cytokines metabolism Dogs Dose-Response Relationship, Drug Enzyme Inhibitors pharmacology Hepatocytes metabolism In Situ Nick-End Labeling Ligands Mice Microscopy, Fluorescence Molecular Sequence Data Neurons metabolism Plasmids metabolism Protein Biosynthesis Protein Structure, Tertiary Proto-Oncogene Proteins c-met metabolism Recombinant Proteins chemistry Transfection Tyrosine chemistry Apoptosis Caspases metabolism Proto-Oncogene Proteins c-met physiology
Sonstiges:	Nachgewiesen in: MEDLINE Sprachen: English Publication Type: Journal Article; Research Support, Non-U.S. Gov't Language: English [Mol Cell Biol] 2004 Dec; Vol. 24 (23), pp. 10328-39. MeSH Terms: Apoptosis* ; Caspases / metabolism ; Proto-Oncogene Proteins c-met / physiology ; Amino Acid Sequence ; Animals ; Aspartic Acid / chemistry ; Aspartic Acid / metabolism ; Blotting, Western ; Caspase 3 ; Cell Survival ; Cells, Cultured ; Cytokines / metabolism ; Dogs ; Dose-Response Relationship, Drug ; Enzyme Inhibitors / pharmacology ; Hepatocytes / metabolism ; In Situ Nick-End Labeling ; Ligands ; Mice ; Microscopy, Fluorescence ; Molecular Sequence Data ; Neurons / metabolism ; Plasmids / metabolism ; Protein Biosynthesis ; Protein Structure, Tertiary ; Proto-Oncogene Proteins c-met / metabolism ; Recombinant Proteins / chemistry ; Transfection ; Tyrosine / chemistry References: EXS. 1993;65:311-28. (PMID: 8380739) ; Biochem Biophys Res Commun. 1998 Apr 7;245(1):211-5. (PMID: 9535810) ; J Biol Chem. 1994 Jan 21;269(3):1815-20. (PMID: 8294430) ; Cell. 1994 Apr 22;77(2):261-71. (PMID: 7513258) ; J Biol Chem. 1995 Jan 13;270(2):507-10. (PMID: 7822270) ; Nature. 1995 Feb 23;373(6516):699-702. (PMID: 7854452) ; Nature. 1995 Feb 23;373(6516):702-5. (PMID: 7854453) ; Proc Natl Acad Sci U S A. 1995 Mar 28;92(7):2597-601. (PMID: 7708691) ; Nature. 1995 Aug 31;376(6543):768-71. (PMID: 7651534) ; Nature. 1996 Nov 14;384(6605):173-6. (PMID: 8906793) ; Cell Growth Differ. 1996 Nov;7(11):1513-23. (PMID: 8930401) ; Oncogene. 2000 Mar 16;19(12):1547-55. (PMID: 10734314) ; EMBO J. 2000 Aug 1;19(15):4056-63. (PMID: 10921886) ; Oncogene. 2000 Nov 20;19(49):5582-9. (PMID: 11114738) ; FEBS Lett. 2001 Feb 23;491(1-2):16-20. (PMID: 11226410) ; J Leukoc Biol. 2001 Mar;69(3):490-6. (PMID: 11261798) ; EMBO J. 2001 Jun 1;20(11):2715-22. (PMID: 11387206) ; Mol Cell. 2001 Jun;7(6):1293-306. (PMID: 11430831) ; J Biol Chem. 2001 Sep 7;276(36):33675-80. (PMID: 11402024) ; Mol Cell. 2001 Nov;8(5):995-1004. (PMID: 11741535) ; Mol Cell. 2002 Feb;9(2):411-21. (PMID: 11864613) ; Nature. 2002 Mar 14;416(6877):187-90. (PMID: 11894096) ; Oncogene. 2002 Apr 4;21(15):2309-19. (PMID: 11948414) ; J Immunol. 2002 Oct 1;169(7):3793-800. (PMID: 12244174) ; Cancer Res. 2002 Dec 1;62(23):7025-30. (PMID: 12460923) ; Nat Rev Mol Cell Biol. 2003 Dec;4(12):915-25. (PMID: 14685170) ; J Cell Sci. 1985 Aug;77:209-23. (PMID: 3841349) ; Proc Natl Acad Sci U S A. 1987 Sep;84(18):6379-83. (PMID: 2819873) ; EMBO J. 1991 Oct;10(10):2867-78. (PMID: 1655405) ; Prog Growth Factor Res. 1991;3(1):67-85. (PMID: 1838014) ; Biochem Biophys Res Commun. 1998 Mar 27;244(3):683-90. (PMID: 9535725) ; Biochem Biophys Res Commun. 1998 May 29;246(3):821-6. (PMID: 9618296) ; Kidney Int. 1998 Oct;54(4):1128-38. (PMID: 9767528) ; Nature. 1998 Oct 22;395(6704):801-4. (PMID: 9796814) ; Biochem J. 1998 Nov 15;336 ( Pt 1):235-9. (PMID: 9806906) ; Mol Biol Cell. 1999 Mar;10(3):551-65. (PMID: 10069803) ; Oncogene. 1999 Jul 22;18(29):4275-81. (PMID: 10435641) ; Mol Cell Biol. 1997 Feb;17(2):799-808. (PMID: 9001234) ; Nat Genet. 1997 May;16(1):68-73. (PMID: 9140397) ; Genes Dev. 1997 Dec 15;11(24):3341-50. (PMID: 9407027) ; Mol Cell Biol. 1998 Apr;18(4):2416-29. (PMID: 9528810) ; J Biol Chem. 1994 Jan 21;269(3):1750-5. (PMID: 8294424) Substance Nomenclature: 0 (Cytokines) ; 0 (Enzyme Inhibitors) ; 0 (Ligands) ; 0 (Recombinant Proteins) ; 30KYC7MIAI (Aspartic Acid) ; 42HK56048U (Tyrosine) ; EC 2.7.10.1 (Proto-Oncogene Proteins c-met) ; EC 3.4.22.- (Casp3 protein, mouse) ; EC 3.4.22.- (Caspase 3) ; EC 3.4.22.- (Caspases) Entry Date(s): Date Created: 20041116 Date Completed: 20050104 Latest Revision: 20181113 Update Code: 20231215 PubMed Central ID: PMC529022

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Proapoptotic function of the MET tyrosine kinase receptor through caspase cleavage.