PMID- 11683915
OWN - NLM
STAT- MEDLINE
DCOM- 20020228
LR  - 20191105
IS  - 1356-9597 (Print)
IS  - 1356-9597 (Linking)
VI  - 6
IP  - 10
DP  - 2001 Oct
TI  - Regulation of Ras and Rho small G proteins by SHP-2.
PG  - 869-76
AB  - BACKGROUND: 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 SHP-2, a protein tyrosine phosphatase, positively regulates 
      the HGF/SF-induced cell scattering through modulating the activity of Rho to form 
      stress fibres and focal adhesions. To further investigate the role of SHP-2 in 
      HGF/SF-induced cell scattering, we have now examined the effect of a dominant 
      active mutant of SHP-2 (SHP-2-DA). RESULTS: Expression of SHP-2-DA markedly 
      increased the formation of lamellipodia with ruffles, while it decreased the 
      accumulation of E-cadherin and beta-catenin at cell-cell adhesion sites in MDCK 
      cells. In addition, expression of SHP-2-DA markedly enhanced cell scattering of 
      MDCK cells in response to HGF/SF. Expression of SHP-2-DA induced the activation 
      of MAP kinase without HGF/SF stimulation, whereas an inhibitor of MEK partly 
      reversed the SHP-2-DA-induced morphological phenotypes. Furthermore, expression 
      of either a dominant-active mutant of Rho or Vav2 also reversed the 
      SHP-2-DA-induced morphological phenotypes. CONCLUSION: These results indicate 
      that SHP-2 plays a crucial role in the HGF/SF-induced cell scattering through the 
      regulation of two distinct small G proteins, Ras and Rho.
FAU - Kodama, A
AU  - Kodama A
AD  - Department of Molecular Biology and Biochemistry, Osaka University Graduate 
      School of Medicine/Faculty of Medicine, Suita 565-0871, Japan.
FAU - Matozaki, T
AU  - Matozaki T
FAU - Shinohara, M
AU  - Shinohara M
FAU - Fukuhara, A
AU  - Fukuhara A
FAU - Tachibana, K
AU  - Tachibana K
FAU - Ichihashi, M
AU  - Ichihashi M
FAU - Nakanishi, H
AU  - Nakanishi H
FAU - Takai, Y
AU  - Takai Y
LA  - eng
PT  - Journal Article
PL  - England
TA  - Genes Cells
JT  - Genes to cells : devoted to molecular & cellular mechanisms
JID - 9607379
RN  - 0 (Cadherins)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Intracellular Signaling Peptides and Proteins)
RN  - 0 (Trans-Activators)
RN  - 0 (beta Catenin)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
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 3.6.5.2 (ras Proteins)
RN  - EC 3.6.5.2 (rho GTP-Binding Proteins)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Animals
MH  - Cadherins/metabolism
MH  - Cell Adhesion/drug effects/genetics
MH  - Cell Line/drug effects
MH  - Cell Size/drug effects
MH  - Cytoskeletal Proteins/metabolism
MH  - Enzyme Inhibitors/pharmacology
MH  - Flavonoids/pharmacology
MH  - Genes, Dominant
MH  - Hepatocyte Growth Factor/metabolism/pharmacology
MH  - Intracellular Signaling Peptides and Proteins
MH  - MAP Kinase Signaling System
MH  - Mutation
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 6
MH  - Protein Tyrosine Phosphatases/drug effects/genetics/*metabolism
MH  - *Trans-Activators
MH  - beta Catenin
MH  - ras Proteins/drug effects/*metabolism
MH  - rho GTP-Binding Proteins/drug effects/genetics/*metabolism
EDAT- 2001/10/31 10:00
MHDA- 2002/03/01 10:01
CRDT- 2001/10/31 10:00
PHST- 2001/10/31 10:00 [pubmed]
PHST- 2002/03/01 10:01 [medline]
PHST- 2001/10/31 10:00 [entrez]
AID - 467 [pii]
AID - 10.1046/j.1365-2443.2001.00467.x [doi]
PST - ppublish
SO  - Genes Cells. 2001 Oct;6(10):869-76. doi: 10.1046/j.1365-2443.2001.00467.x.