PMID- 10930454
OWN - NLM
STAT- MEDLINE
DCOM- 20001222
LR  - 20211203
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 11
IP  - 8
DP  - 2000 Aug
TI  - Involvement of an SHP-2-Rho small G protein pathway in hepatocyte growth 
      factor/scatter factor-induced cell scattering.
PG  - 2565-75
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) induces cell scattering through 
      the tyrosine kinase-type HGF/SF receptor c-Met. We have previously shown that Rho 
      small G protein (Rho) is involved in the HGF/SF-induced scattering of Madin-Darby 
      canine kidney (MDCK) cells by regulating at least the assembly and disassembly of 
      stress fibers and focal adhesions, but it remains unknown how c-Met regulates Rho 
      activity. We have found here a novel signaling pathway of c-Met consisting of 
      SHP-2-Rho that regulates the assembly and disassembly of stress fibers and focal 
      adhesions in MDCK cells. SHP-2 is a protein-tyrosine phosphatase that contains 
      src homology-2 domains. Expression of a dominant negative mutant of SHP-2 
      (SHP-2-C/S) markedly increased the formation of stress fibers and focal adhesions 
      in MDCK cells and inhibited their scattering. C3, a Clostridium botulinum 
      ADP-ribosyltransferase, and Y-27632, a specific inhibitor for ROCK, reversed the 
      stimulatory effect of SHP-2-C/S on stress fiber formation and the inhibitory 
      effect on cell scattering. Vav2 is a GDP/GTP exchange protein for Rho. Expression 
      of a dominant negative mutant of Vav2 blocked the stimulatory effect of SHP-2-C/S 
      on stress fiber formation. Conversely, expression of mutants of Vav2 that 
      increased stress fiber formation inhibited HGF/SF-induced cell scattering. These 
      results indicate that SHP-2 physiologically modulates the activity of Rho to form 
      stress fibers and focal adhesions and thereby regulates HGF/SF-induced cell 
      scattering. In addition, Vav2 may be involved in the SHP-2-Rho pathway.
FAU - Kodama, A
AU  - Kodama A
AD  - Department of Molecular Biology and Biochemistry, Osaka University Graduate 
      School of Medicine/Faculty of Medicine, Suita, Japan.
FAU - Matozaki, T
AU  - Matozaki T
FAU - Fukuhara, A
AU  - Fukuhara A
FAU - Kikyo, M
AU  - Kikyo M
FAU - Ichihashi, M
AU  - Ichihashi M
FAU - Takai, Y
AU  - Takai Y
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 (Amides)
RN  - 0 (Cell Cycle Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Proto-Oncogene Proteins c-vav)
RN  - 0 (Pyridines)
RN  - 138381-45-0 (Y 27632)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.4.2.- (ADP Ribose Transferases)
RN  - EC 2.4.2.- (exoenzyme C3, Clostridium botulinum)
RN  - EC 2.7.11.1 (Protein Serine-Threonine Kinases)
RN  - EC 2.7.11.1 (rho-Associated Kinases)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 6)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatases)
RN  - EC 3.4.24.69 (Botulinum Toxins)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
SB  - IM
MH  - ADP Ribose Transferases/pharmacology
MH  - Amides/pharmacology
MH  - Animals
MH  - *Botulinum Toxins
MH  - Cell Adhesion/drug effects
MH  - *Cell Cycle Proteins
MH  - Cell Line
MH  - Cytoskeleton/drug effects
MH  - Dogs
MH  - Enzyme Inhibitors/pharmacology
MH  - Hepatocyte Growth Factor/*physiology
MH  - Intracellular Signaling Peptides and Proteins
MH  - Microscopy, Confocal
MH  - Models, Biological
MH  - Mutation
MH  - Protein Serine-Threonine Kinases/drug effects/metabolism/physiology
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6
MH  - Protein Tyrosine Phosphatases/genetics/*physiology
MH  - Proto-Oncogene Proteins/genetics/physiology
MH  - Proto-Oncogene Proteins c-vav
MH  - Pyridines/pharmacology
MH  - Signal Transduction/drug effects
MH  - Transfection
MH  - rho GTP-Binding Proteins/drug effects/metabolism/*physiology
MH  - rho-Associated Kinases
PMC - PMC14940
EDAT- 2000/08/10 11:00
MHDA- 2001/02/28 10:01
CRDT- 2000/08/10 11:00
PHST- 2000/08/10 11:00 [pubmed]
PHST- 2001/02/28 10:01 [medline]
PHST- 2000/08/10 11:00 [entrez]
AID - 1266 [pii]
AID - 10.1091/mbc.11.8.2565 [doi]
PST - ppublish
SO  - Mol Biol Cell. 2000 Aug;11(8):2565-75. doi: 10.1091/mbc.11.8.2565.