PMID- 9693375
OWN - NLM
STAT- MEDLINE
DCOM- 19980930
LR  - 20191210
IS  - 1059-1524 (Print)
IS  - 1059-1524 (Linking)
VI  - 9
IP  - 8
DP  - 1998 Aug
TI  - Activation of both MAP kinase and phosphatidylinositide 3-kinase by Ras is 
      required for hepatocyte growth factor/scatter factor-induced adherens junction 
      disassembly.
PG  - 2185-200
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) stimulates the motility of 
      epithelial cells, initially inducing centrifugal spreading of colonies followed 
      by disruption of cell-cell junctions and subsequent cell scattering. In 
      Madin-Darby canine kidney cells, HGF/SF-induced motility involves actin 
      reorganization mediated by Ras, but whether Ras and downstream signals regulate 
      the breakdown of intercellular adhesions has not been established. Both HGF/SF 
      and V12Ras induced the loss of the adherens junction proteins E-cadherin and 
      beta-catenin from intercellular junctions during cell spreading, and the HGF/SF 
      response was blocked by dominant-negative N17Ras. Desmosomes and tight junctions 
      were regulated separately from adherens junctions, because they were not 
      disrupted by V12Ras. MAP kinase, phosphatidylinositide 3-kinase (PI 3-kinase), 
      and Rac were required downstream of Ras, because loss of adherens junctions was 
      blocked by the inhibitors PD098059 and LY294002 or by dominant-inhibitory mutants 
      of MAP kinase kinase 1 or Rac1. All of these inhibitors also prevented 
      HGF/SF-induced cell scattering. Interestingly, activated Raf or the activated 
      p110alpha subunit of PI 3-kinase alone did not induce disruption of adherens 
      junctions. These results indicate that activation of both MAP kinase and PI 
      3-kinase by Ras is required for adherens junction disassembly and that this is 
      essential for the motile response to HGF/SF.
FAU - Potempa, S
AU  - Potempa S
AD  - Ludwig Institute for Cancer Research, University College London Branch, London 
      W1P 8BT, United Kingdom.
FAU - Ridley, A J
AU  - Ridley AJ
LA  - eng
PT  - Journal Article
PL  - United States
TA  - Mol Biol Cell
JT  - Molecular biology of the cell
JID - 9201390
RN  - 0 (Cadherins)
RN  - 0 (Chromones)
RN  - 0 (Cytoskeletal Proteins)
RN  - 0 (Enzyme Inhibitors)
RN  - 0 (Flavonoids)
RN  - 0 (Morpholines)
RN  - 0 (Phosphoinositide-3 Kinase Inhibitors)
RN  - 0 (Trans-Activators)
RN  - 0 (beta Catenin)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
RN  - EC 3.6.1.- (GTP-Binding Proteins)
RN  - EC 3.6.5.2 (rac GTP-Binding Proteins)
RN  - EC 3.6.5.2 (ras Proteins)
RN  - SJE1IO5E3I (2-(2-amino-3-methoxyphenyl)-4H-1-benzopyran-4-one)
SB  - IM
MH  - Animals
MH  - Cadherins/physiology
MH  - Calcium-Calmodulin-Dependent Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Cell Adhesion/drug effects/*physiology
MH  - Cell Line
MH  - Chromones/pharmacology
MH  - Cytoskeletal Proteins/physiology
MH  - Desmosomes/drug effects/physiology
MH  - Dogs
MH  - Enzyme Activation
MH  - Enzyme Inhibitors/pharmacology
MH  - Epithelial Cells/cytology/drug effects/physiology
MH  - Flavonoids/pharmacology
MH  - GTP-Binding Proteins/physiology
MH  - Hepatocyte Growth Factor/*pharmacology/physiology
MH  - Intercellular Junctions/drug effects/*physiology
MH  - Kidney
MH  - Morpholines/pharmacology
MH  - Phosphatidylinositol 3-Kinases/*metabolism
MH  - Phosphoinositide-3 Kinase Inhibitors
MH  - Signal Transduction
MH  - *Trans-Activators
MH  - Transfection
MH  - beta Catenin
MH  - rac GTP-Binding Proteins
MH  - ras Proteins/*physiology
PMC - PMC25472
EDAT- 1998/08/07 00:00
MHDA- 1998/08/07 00:01
CRDT- 1998/08/07 00:00
PHST- 1998/08/07 00:00 [pubmed]
PHST- 1998/08/07 00:01 [medline]
PHST- 1998/08/07 00:00 [entrez]
AID - 0658 [pii]
AID - 10.1091/mbc.9.8.2185 [doi]
PST - ppublish
SO  - Mol Biol Cell. 1998 Aug;9(8):2185-200. doi: 10.1091/mbc.9.8.2185.