PMID- 10618718
OWN - NLM
STAT- MEDLINE
DCOM- 20000204
LR  - 20131121
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 18
IP  - 54
DP  - 1999 Dec 16
TI  - Met-induced JNK activation is mediated by the adapter protein Crk and correlates 
      with the Gab1 - Crk signaling complex formation.
PG  - 7775-86
AB  - Constitutive activation of the Met tyrosine kinase results in transformation of
      cells of diverse origin. Recent studies have demonstrated a role for the c-Jun
      N-terminal kinase (JNK) in Met-induced transformation, but little is known about 
      the molecular mechanisms that connect Met to JNK activation. Our studies show
      that activated Met associates with, and phosphorylates, the docking protein Gab1,
      which in turn binds to the src homology 2 (SH2)-domain of the adapter protein Crk
      and recruits Crk to the Met signaling complex. Formation of the Gab1 - Crk
      complex correlates with Met-induced JNK activation, and mutant forms of Met that 
      fail to induce the complex formation also fail to activate JNK. Importantly,
      expression of a loss-of-function mutant of Crk severely impairs activation of the
      JNK pathway by Met. We also show here that Met controls the transcription of the 
      matrix metalloproteinase-1 (MMP-1) gene in carcinoma cells and that this
      transcriptional regulation occurs in a Crk - JNK-dependent manner through an AP-1
      element in the MMP-1 promoter. Taken together, our data implicate the Gab1 - Crk 
      signaling complex in Met-induced JNK activation and suggest that the Gab1 - Crk
      complex formation may be an important event in regulating the tumorigenic
      phenotype of Met-transformed cells.
FAU - Garcia-Guzman, M
AU  - Garcia-Guzman M
AD  - Cancer Research Center, The Burnham Institute, 10901 North Torrey Pines Road, La 
      Jolla, California, CA 92037, USA.
FAU - Dolfi, F
AU  - Dolfi F
FAU - Zeh, K
AU  - Zeh K
FAU - Vuori, K
AU  - Vuori K
LA  - eng
GR  - CA71560/CA/NCI NIH HHS/United States
GR  - CA76037/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (Adaptor Proteins, Signal Transducing)
RN  - 0 (CRKL protein)
RN  - 0 (GAB1 protein, human)
RN  - 0 (Nuclear Proteins)
RN  - 0 (Phosphoproteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-crk)
RN  - 0 (Transcription Factor AP-1)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - AE28F7PNPL (Methionine)
RN  - EC 1.13.12.- (Luciferases)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - EC 3.4.24.7 (Matrix Metalloproteinase 1)
SB  - IM
MH  - *Adaptor Proteins, Signal Transducing
MH  - Animals
MH  - COS Cells
MH  - Enhancer Elements, Genetic
MH  - Gene Expression Regulation
MH  - HeLa Cells
MH  - Hepatocyte Growth Factor/pharmacology
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases
MH  - Luciferases/genetics
MH  - Matrix Metalloproteinase 1/genetics
MH  - *Methionine
MH  - Mitogen-Activated Protein Kinases/*metabolism
MH  - Nuclear Proteins/*metabolism
MH  - Phosphoproteins/*metabolism
MH  - Promoter Regions, Genetic
MH  - Proto-Oncogene Proteins/*metabolism
MH  - Proto-Oncogene Proteins c-crk
MH  - Proto-Oncogene Proteins c-met/*metabolism
MH  - Signal Transduction
MH  - Transcription Factor AP-1/genetics/metabolism
MH  - Transfection
MH  - Tumor Cells, Cultured
MH  - src Homology Domains
EDAT- 2000/01/05 00:00
MHDA- 2000/01/05 00:01
CRDT- 2000/01/05 00:00
PHST- 2000/01/05 00:00 [pubmed]
PHST- 2000/01/05 00:01 [medline]
PHST- 2000/01/05 00:00 [entrez]
AID - 10.1038/sj.onc.1203198 [doi]
PST - ppublish
SO  - Oncogene. 1999 Dec 16;18(54):7775-86. doi: 10.1038/sj.onc.1203198.