PMID- 8387483
OWN - NLM
STAT- MEDLINE
DCOM- 19930604
LR  - 20211203
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 268
IP  - 13
DP  - 1993 May 5
TI  - Hepatocyte growth factor/scatter factor stimulates the Ras-guanine nucleotide 
      exchanger.
PG  - 9165-8
AB  - Hepatocyte growth factor/scatter factor (HGF/SF) induces mitogenesis and cell 
      dissociation upon binding to the protein-tyrosine kinase receptor encoded by the 
      MET proto-oncogene (p190MET). The signal transduction pathways downstream from 
      the receptor activation are largely unknown. We show that HGF/SF activates Ras 
      protein. HGF/SF stimulation of metabolically labeled A549 cells raised the amount 
      of Ras-bound radiolabeled guanine nucleotides by over 5-fold. Furthermore, 
      following HGF/SF stimulation of these cells, 50% of Ras was in the GTP-bound 
      active state. The uptake by Ras of radiolabeled GTP was also increased by 5-fold 
      following HGF/SF stimulation in digitonin-permeabilized A549 cells. Moreover, 
      HGF/SF treatment of A549 cells leads to stimulation of the cytosolic Ras-guanine 
      nucleotide exchange activity, measured as accelerated release of [3H]GDP from 
      purified recombinant Ras protein in vitro, in a dose- and time-dependent manner. 
      Likewise, treatment with the protein-tyrosine kinase inhibitor 
      3-(1',4'-dihydroxytetralyl)methylene-2-oxindole of GTL-16 cells (featuring a 
      p190MET receptor constitutively active) significantly decreased the cytosolic 
      Ras-guanine nucleotide exchange activity. These data demonstrate that HGF/SF 
      activates Ras protein by shifting the equilibrium toward the GTP-bound state and 
      increases the uptake of guanine nucleotides by Ras, through mechanism(s) 
      including the activation of a Ras-guanine nucleotide exchanger.
FAU - Graziani, A
AU  - Graziani A
AD  - Department of Biomedical Sciences and Oncology, University of Torino Medical 
      School, Italy.
FAU - Gramaglia, D
AU  - Gramaglia D
FAU - dalla Zonca, P
AU  - dalla Zonca P
FAU - Comoglio, P M
AU  - Comoglio PM
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (GTPase-Activating Proteins)
RN  - 0 (Indoles)
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proteins)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 0 (Receptors, Cell Surface)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Tetrahydronaphthalenes)
RN  - 0 (ras GTPase-Activating Proteins)
RN  - 146-91-8 (Guanosine Diphosphate)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 86-01-1 (Guanosine Triphosphate)
RN  - EC 2.7.10.1 (Protein-Tyrosine Kinases)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 3.6.5.2 (HRAS protein, human)
RN  - EC 3.6.5.2 (Proto-Oncogene Proteins p21(ras))
SB  - IM
MH  - Biological Transport/drug effects
MH  - Cell Line
MH  - GTPase-Activating Proteins
MH  - Guanosine Diphosphate/*metabolism
MH  - Guanosine Triphosphate/*metabolism
MH  - Hepatocyte Growth Factor/*pharmacology
MH  - Humans
MH  - Indoles/*pharmacology
MH  - Kinetics
MH  - Lung Neoplasms
MH  - Protein-Tyrosine Kinases/antagonists & inhibitors/genetics/*metabolism
MH  - Proteins/*metabolism
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins/genetics/*metabolism
MH  - Proto-Oncogene Proteins c-met
MH  - Proto-Oncogene Proteins p21(ras)/*metabolism
MH  - Proto-Oncogenes
MH  - Receptors, Cell Surface/drug effects/genetics/*metabolism
MH  - Recombinant Proteins/metabolism
MH  - Tetrahydronaphthalenes/*pharmacology
MH  - Tumor Cells, Cultured
MH  - ras GTPase-Activating Proteins
EDAT- 1993/05/05 00:00
MHDA- 1993/05/05 00:01
CRDT- 1993/05/05 00:00
PHST- 1993/05/05 00:00 [pubmed]
PHST- 1993/05/05 00:01 [medline]
PHST- 1993/05/05 00:00 [entrez]
AID - S0021-9258(18)98327-4 [pii]
PST - ppublish
SO  - J Biol Chem. 1993 May 5;268(13):9165-8.