PMID- 22223753
OWN - NLM
STAT- MEDLINE
DCOM- 20120531
LR  - 20211203
IS  - 1530-6860 (Electronic)
IS  - 0892-6638 (Linking)
VI  - 26
IP  - 4
DP  - 2012 Apr
TI  - Met degradation: more than one stone to shoot a receptor down.
PG  - 1387-99
LID - 10.1096/fj.11-197723 [doi]
AB  - The receptor tyrosine kinase Met and its high-affinity ligand, the hepatocyte 
      growth factor/scatter factor (HGF/SF), are essential to embryonic development. 
      Deregulation of their signaling is associated with tumorigenesis and metastasis, 
      notably through receptor overexpression. It is thus important to understand the 
      mechanisms controlling Met expression. The ligand-dependent internalization of 
      Met and its subsequent degradation in the lysosomal compartment are well 
      described. This process is known to attenuate downstream Met signaling pathways. 
      Yet internalized Met takes part directly in intracellular signaling by 
      chaperoning signaling factors in the course of its trafficking. Furthermore, 
      recent studies describe various new degradation mechanisms of membrane-anchored 
      Met, involving proteolytic cleavages or association with novel partners. Although 
      all these degradations are ligand-independent, they share, to different extents, 
      some common features with canonical HGF/SF-dependent degradation. Interestingly, 
      activated Met variants display resistance to degradation, suggesting defective 
      degradation is involved in tumorigenesis. Conversely, forced degradation of Met 
      through reinduction of one or more degradation pathways is a promising 
      therapeutic strategy.
FAU - Lefebvre, Jonathan
AU  - Lefebvre J
AD  - CNRS UMR 8161, Institut de Biologie de Lille, Institut Pasteur de Lille, B.P.447, 
      59021 Lille, France.
FAU - Ancot, Frederic
AU  - Ancot F
FAU - Leroy, Catherine
AU  - Leroy C
FAU - Muharram, Ghaffar
AU  - Muharram G
FAU - Lemiere, Arnaud
AU  - Lemiere A
FAU - Tulasne, David
AU  - Tulasne D
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Review
DEP - 20120105
PL  - United States
TA  - FASEB J
JT  - FASEB journal : official publication of the Federation of American Societies for 
      Experimental Biology
JID - 8804484
RN  - 0 (Leucine-Rich Repeat Proteins)
RN  - 0 (Ligands)
RN  - 0 (Proteins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
SB  - IM
MH  - Animals
MH  - Hepatocyte Growth Factor/metabolism
MH  - Humans
MH  - Leucine-Rich Repeat Proteins
MH  - Ligands
MH  - Lysosomes/metabolism
MH  - Neoplasms/metabolism/therapy
MH  - Proteins/metabolism
MH  - Proto-Oncogene Proteins c-met/genetics/*metabolism
MH  - Signal Transduction/*physiology
EDAT- 2012/01/10 06:00
MHDA- 2012/06/01 06:00
CRDT- 2012/01/07 06:00
PHST- 2012/01/07 06:00 [entrez]
PHST- 2012/01/10 06:00 [pubmed]
PHST- 2012/06/01 06:00 [medline]
AID - fj.11-197723 [pii]
AID - 10.1096/fj.11-197723 [doi]
PST - ppublish
SO  - FASEB J. 2012 Apr;26(4):1387-99. doi: 10.1096/fj.11-197723. Epub 2012 Jan 5.