Visit our Expo - Redox and Inflammation signaling 2012

Session II : Receptor signaling and G proteins Poster II, 22
Sequential caspase cleavages generate pro-apoptotic factor from MET tyrosine kinase
receptor
Bénédicte FOVEAU*, Catherine LEROY*, Julien DEHEUNINCK, Zongling JI,
Véronique FAFEUR and David TULASNE.
*These authors contributed equally to the study
CNRS UMR 8117, Institut de Biologie de Lille, Institut Pasteur de Lille, B.P.447, 59021
Lille, FRANCE.
The receptor of hepatocyte growth factor/scatter factor (HGF/SF), the MET tyrosine kinase
receptor, is known to be essential for normal development and cell survival. We previously
showed that stress stimuli cause a cleavage in the MET juxtamembrane domain that converts
the receptor into a pro-apoptotic 40 kDa fragment (p40 MET). We report here an additional
caspase cleavage of MET occurring in its extreme C-terminal region. The cleavage occurs at
aspartic residue 1374 within the DNID sequence of mouse MET. Although this cleavage
removes only the five last amino acids, it has important functional consequences. First, the Cterminal
cleavage favors the juxtamembrane one, leading to efficient generation of the proapoptotic
p40 MET fragment. Second, the p40 MET generated by the two steps cleavage has
enhanced pro-apoptotic activity. These results revealed a tight regulation of MET caspase
cleavages resulting in the reshaping of a survival receptor to a pro-apoptotic factor.
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