Caspase cleavage of the MET receptor generates an HGF interfering fragment.
The MET tyrosine kinase receptor activated by its ligand HGF/SF, induces several cellular responses, including survival. Nonetheless, the MET receptor is cleaved in stress conditions by caspases within its intracellular region, generating a 40kDa fragment, p40 MET, with pro-apoptotic properties. Here, we established that this cleavage splits the receptor at the juxtamembrane ESVD site, causing the concomitant generation of p100 MET, corresponding to the entire extracellular region of the MET receptor still spanning the membrane. This fragment is able to bind HGF/SF and to prevent HGF-dependent signaling downstream of full MET, demonstrating its function as a decoy receptor.
Deheuninck
Julien
J
UMR-8161, Institut de Biologie de Lille, CNRS, Université de Lille-1, Université de Lille-2, Institut Pasteur de Lille, BP 447, F-59021 Lille Cedex, France.
Foveau
Bénédicte
B
Goormachtigh
Gautier
G
Leroy
Catherine
C
Ji
Zongling
Z
Tulasne
David
D
Fafeur
Véronique
V
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D020169:Caspases / Q000378:metabolism*; D002458:Cell Fractionation; D002478:Cells, Cultured; D004285:Dogs; D018014:Gene Transfer Techniques; D017228:Hepatocyte Growth Factor / Q000037:antagonists & inhibitors / Q000737:chemistry / Q000378:metabolism*; D006801:Humans; D010446:Peptide Fragments / Q000096:biosynthesis* / Q000235:genetics / Q000494:pharmacology; D019859:Proto-Oncogene Proteins c-met / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D053221:TNF-Related Apoptosis-Inducing Ligand / Q000494:pharmacology
D010446:Peptide Fragments; D053221:TNF-Related Apoptosis-Inducing Ligand; C505653:TNFSF10 protein, human; D017228:Hepatocyte Growth Factor; D019859:Proto-Oncogene Proteins c-met; D020169:Caspases