PMID- 10069803
OWN - NLM
STAT- MEDLINE
DCOM- 19990401
LR  - 20181113
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 10
IP  - 3
DP  - 1999 Mar
TI  - The multisubstrate docking site of the MET receptor is dispensable for
      MET-mediated RAS signaling and cell scattering.
PG  - 551-65
AB  - The scatter factor/hepatocyte growth factor regulates scattering and
      morphogenesis of epithelial cells through activation of the MET tyrosine kinase
      receptor. In particular, the noncatalytic C-terminal tail of MET contains two
      autophosphorylation tyrosine residues, which form a multisubstrate-binding site
      for several cytoplasmic effectors and are thought to be essential for signal
      transduction. We show here that a MET receptor mutated on the four C-terminal
      tyrosine residues, Y1311F, Y1347F, Y1354F, and Y1363F, can induce efficiently a
      transcriptional response and cell scattering, whereas it cannot induce cell
      morphogenesis. Although the mutated receptor had lost its ability to recruit
      and/or activate known signaling molecules, such as GRB2, SHC, GAB1, and PI3K, by 
      using a sensitive association-kinase assay we found that the mutated receptor can
      still associate and phosphorylate a approximately 250-kDa protein. By further
      examining signal transduction mediated by the mutated MET receptor, we
      established that it can transmit efficient RAS signaling and that cell scattering
      by the mutated MET receptor could be inhibited by a pharmacological inhibitor of 
      the MEK-ERK (MAP kinase kinase-extracellular signal-regulated kinase) pathway. We
      propose that signal transduction by autophosphorylation of the C-terminal
      tyrosine residues is not the sole mechanism by which the activated MET receptor
      can transmit RAS signaling and cell scattering.
FAU - Tulasne, D
AU  - Tulasne D
AD  - Centre National de la Recherche Scientifique EP 560, Institut de Biologie de
      Lille, Institut Pasteur de Lille, 59021 Lille, France.
FAU - Paumelle, R
AU  - Paumelle R
FAU - Weidner, K M
AU  - Weidner KM
FAU - Vandenbunder, B
AU  - Vandenbunder B
FAU - Fafeur, V
AU  - Fafeur V
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (Adaptor Proteins, Vesicular Transport)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-ets)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Shc Signaling Adaptor Proteins)
RN  - 0 (Transcription Factor AP-1)
RN  - 0 (Transcription Factors)
RN  - 151441-47-3 (GRB10 Adaptor Protein)
RN  - 42HK56048U (Tyrosine)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.1.- (Phosphatidylinositol 3-Kinases)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 3.6.5.2 (ras Proteins)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - *Adaptor Proteins, Vesicular Transport
MH  - Animals
MH  - Binding Sites
MH  - Cell Line
MH  - Cell Movement/*physiology
MH  - Dogs
MH  - GRB10 Adaptor Protein
MH  - Hepatocyte Growth Factor/metabolism/pharmacology
MH  - Mutation
MH  - Phosphatidylinositol 3-Kinases/metabolism
MH  - Phosphoproteins/metabolism
MH  - Phosphorylation
MH  - Proteins/metabolism
MH  - Proto-Oncogene Proteins/metabolism
MH  - Proto-Oncogene Proteins c-ets
MH  - Proto-Oncogene Proteins c-met/*genetics/*metabolism
MH  - Recombinant Proteins/genetics/metabolism
MH  - Shc Signaling Adaptor Proteins
MH  - *Signal Transduction
MH  - Transcription Factor AP-1/metabolism
MH  - Transcription Factors/metabolism
MH  - Transcriptional Activation
MH  - Transfection
MH  - Tyrosine/metabolism
MH  - ras Proteins/genetics/*metabolism
PMC - PMC25187
EDAT- 1999/03/09 00:00
MHDA- 1999/03/09 00:01
CRDT- 1999/03/09 00:00
PHST- 1999/03/09 00:00 [pubmed]
PHST- 1999/03/09 00:01 [medline]
PHST- 1999/03/09 00:00 [entrez]
AID - 10.1091/mbc.10.3.551 [doi]
PST - ppublish
SO  - Mol Biol Cell. 1999 Mar;10(3):551-65. doi: 10.1091/mbc.10.3.551.