PMID- 19450681
OWN - NLM
STAT- MEDLINE
DCOM- 20090814
LR  - 20161125
IS  - 1873-3913 (Electronic)
IS  - 0898-6568 (Linking)
VI  - 21
IP  - 9
DP  - 2009 Sep
TI  - Phosphorylation of the MET receptor on juxtamembrane tyrosine residue 1001 
      inhibits its caspase-dependent cleavage.
PG  - 1455-63
LID - 10.1016/j.cellsig.2009.05.005 [doi]
AB  - The MET tyrosine kinase is the hepatocyte growth factor/scatter factor (HGF/SF) 
      receptor, which elicits multiple biological responses in epithelial cells, 
      including cell survival. We previously demonstrated that in stress conditions, 
      the MET receptor is cleaved by caspases within its juxtamembrane region, 
      generating a pro-apoptotic intracellular fragment of 40 kDa. The caspase cleavage 
      site at aspartic acid D1000 is adjacent to tyrosine Y1001, which when 
      phosphorylated upon MET activation, is involved in CBL recruitment, allowing 
      receptor ubiquitination and down regulation. Scanning mutagenesis of the MET 
      juxtamembrane region led us to demonstrate that V999 and D1000 are essential for 
      the caspase cleavage, while D1000 and Y1001 are essential for CBL recruitment. By 
      examining whether overlapping of these sites leads to a functional interference, 
      an inverse relationship was found between generation of p40 MET and 
      phosphorylation of MET, with a direct involvement of phosphorylated Y1001 in 
      protecting MET against its caspase cleavage. A molecular modeling analysis of 
      caspase 3 interaction with the juxtamembrane region of MET confirmed that 
      phosphorylation of this tyrosine is not compatible with its recognition by active 
      caspase 3. These data demonstrate a direct protection mechanism of an activated 
      phosphorylated MET receptor, against its caspase-dependent cleavage.
FAU - Deheuninck, Julien
AU  - Deheuninck J
AD  - CNRS UMR 8161, Institut de Biologie de Lille, Universite Lille-Nord de France, 
      Institut Pasteur de Lille, IFR142, LILLE, France.
FAU - Goormachtigh, Gautier
AU  - Goormachtigh G
FAU - Foveau, Benedicte
AU  - Foveau B
FAU - Ji, Zongling
AU  - Ji Z
FAU - Leroy, Catherine
AU  - Leroy C
FAU - Ancot, Frederic
AU  - Ancot F
FAU - Villeret, Vincent
AU  - Villeret V
FAU - Tulasne, David
AU  - Tulasne D
FAU - Fafeur, Veronique
AU  - Fafeur V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090518
PL  - England
TA  - Cell Signal
JT  - Cellular signalling
JID - 8904683
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Growth Factor)
RN  - 42HK56048U (Tyrosine)
RN  - EC 2.3.2.27 (Proto-Oncogene Proteins c-cbl)
RN  - EC 2.7.10.1 (MET protein, human)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 3.4.22.- (Caspases)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Caspases/*metabolism
MH  - Cell Line
MH  - Cell Membrane/physiology
MH  - Computer Simulation
MH  - Dogs
MH  - HeLa Cells
MH  - Humans
MH  - Phosphorylation
MH  - Protein Interaction Domains and Motifs
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-cbl/metabolism
MH  - Proto-Oncogene Proteins c-met
MH  - Receptors, Growth Factor/*metabolism
MH  - Tyrosine/*metabolism
MH  - Ubiquitination
EDAT- 2009/05/20 09:00
MHDA- 2009/08/15 09:00
CRDT- 2009/05/20 09:00
PHST- 2009/04/21 00:00 [received]
PHST- 2009/05/11 00:00 [accepted]
PHST- 2009/05/20 09:00 [entrez]
PHST- 2009/05/20 09:00 [pubmed]
PHST- 2009/08/15 09:00 [medline]
AID - S0898-6568(09)00169-7 [pii]
AID - 10.1016/j.cellsig.2009.05.005 [doi]
PST - ppublish
SO  - Cell Signal. 2009 Sep;21(9):1455-63. doi: 10.1016/j.cellsig.2009.05.005. Epub 
      2009 May 18.