PMID- 19297528
OWN - NLM
STAT- MEDLINE
DCOM- 20090720
LR  - 20211020
IS  - 1939-4586 (Electronic)
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 20
IP  - 9
DP  - 2009 May
TI  - Down-regulation of the met receptor tyrosine kinase by presenilin-dependent 
      regulated intramembrane proteolysis.
PG  - 2495-507
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) acts through the 
      membrane-anchored Met receptor tyrosine kinase to induce invasive growth. 
      Deregulation of this signaling is associated with tumorigenesis and involves, in 
      most cases, overexpression of the receptor. We demonstrate that Met is processed 
      in epithelial cells by presenilin-dependent regulated intramembrane proteolysis 
      (PS-RIP) independently of ligand stimulation. The proteolytic process involves 
      sequential cleavage by metalloproteases and the gamma-secretase complex, leading 
      to generation of labile fragments. In normal epithelial cells, although 
      expression of cleavable Met by PS-RIP is down-regulated, uncleavable Met 
      displayed membrane accumulation and induced ligand-independent motility and 
      morphogenesis. Inversely, in transformed cells, the Met inhibitory antibody DN30 
      is able to promote Met PS-RIP, resulting in down-regulation of the receptor and 
      inhibition of the Met-dependent invasive growth. This demonstrates the original 
      involvement of a proteolytic process in degradation of the Met receptor 
      implicated in negative regulation of invasive growth.
FAU - Foveau, Benedicte
AU  - Foveau B
AD  - CNRS UMR 8161, Institut de Biologie de Lille-Institut Pasteur de Lille-Universite 
      de Lille 1-Universite de Lille 2, 59021 Lille cedex, France.
FAU - Ancot, Frederic
AU  - Ancot F
FAU - Leroy, Catherine
AU  - Leroy C
FAU - Petrelli, Annalisa
AU  - Petrelli A
FAU - Reiss, Karina
AU  - Reiss K
FAU - Vingtdeux, Valerie
AU  - Vingtdeux V
FAU - Giordano, Silvia
AU  - Giordano S
FAU - Fafeur, Veronique
AU  - Fafeur V
FAU - Tulasne, David
AU  - Tulasne D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20090318
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Antibodies)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Ligands)
RN  - 0 (Peptide Fragments)
RN  - 0 (Presenilins)
RN  - 0 (Proteasome Inhibitors)
RN  - 0 (Recombinant Proteins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 3.4.- (Amyloid Precursor Protein Secretases)
RN  - EC 3.4.- (Metalloproteases)
RN  - EC 3.4.24.- (ADAM Proteins)
RN  - EC 3.4.24.86 (ADAM17 Protein)
SB  - IM
MH  - ADAM Proteins/antagonists & inhibitors
MH  - ADAM17 Protein
MH  - Amyloid Precursor Protein Secretases/antagonists & inhibitors
MH  - Animals
MH  - Antibodies
MH  - Cell Line
MH  - Cell Membrane/drug effects/*enzymology
MH  - Cell Proliferation/drug effects
MH  - Dogs
MH  - *Down-Regulation/drug effects
MH  - Enzyme Activation/drug effects
MH  - Enzyme Inhibitors/pharmacology
MH  - Hepatocyte Growth Factor/pharmacology
MH  - Humans
MH  - Ligands
MH  - Metalloproteases/antagonists & inhibitors
MH  - Mice
MH  - Peptide Fragments/metabolism
MH  - Presenilins/*metabolism
MH  - Proteasome Inhibitors
MH  - *Protein Processing, Post-Translational/drug effects
MH  - Protein Stability/drug effects
MH  - Proto-Oncogene Proteins c-met/*metabolism
MH  - Recombinant Proteins/metabolism
PMC - PMC2675628
EDAT- 2009/03/20 09:00
MHDA- 2009/07/21 09:00
PMCR- 2009/07/16
CRDT- 2009/03/20 09:00
PHST- 2009/03/20 09:00 [entrez]
PHST- 2009/03/20 09:00 [pubmed]
PHST- 2009/07/21 09:00 [medline]
PHST- 2009/07/16 00:00 [pmc-release]
AID - E08-09-0969 [pii]
AID - 3472063 [pii]
AID - 10.1091/mbc.e08-09-0969 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2009 May;20(9):2495-507. doi: 10.1091/mbc.e08-09-0969. Epub 2009 
      Mar 18.