PMID- 1331934
OWN - NLM
STAT- MEDLINE
DCOM- 19921208
LR  - 20211203
IS  - 0950-9232 (Print)
IS  - 0950-9232 (Linking)
VI  - 7
IP  - 11
DP  - 1992 Nov
TI  - Met and hepatocyte growth factor/scatter factor signal transduction in normal 
      melanocytes and melanoma cells.
PG  - 2195-206
AB  - The proto-oncogene c-MET encodes a transmembrane tyrosine kinase receptor for 
      hepatocyte growth factor/scatter factor (HGF/SF). HGF/SF stimulates the 
      proliferation and motility of various cell types. Because HGF/SF is also a 
      melanocyte mitogen, we investigated the biological role of HGF/SF, including 
      c-Met expression, activation and signal transduction, in normal and malignant 
      human melanocytes. We show that HGF/SF is mitogenic in the presence of 
      synergistic factors, such as basic fibroblast growth factor (bFGF) and mast cell 
      growth factor (MGF) and that, by itself, it stimulates the motility of normal 
      human melanocytes. The ligand also maintained high levels of tyrosinase activity 
      and melanin content in theses cells. Signal transduction by HGF/SF included 
      phosphorylation of tyrosyl residues on c-Met, a cascade of tyrosine 
      phosphorylations on several other proteins and activation of 
      microtubule-associated protein kinase/extracellular signal-regulated kinase. Met 
      expression and activity are normal in human melanomas, and constitutive activity 
      of HGF/SF in retrovirally infected autonomously proliferative mouse melanocytes 
      is insufficient to confer the malignant phenotype. Our findings suggest that 
      activation of Met in response to HGF/SF may contribute to malignant progression 
      synergistically with the aberrant expression of bFGF in malignant melanocytes and 
      that, in addition, the peptide may promote dispersion of factor-dependent 
      melanocytes from early stages of primary melanomas to ectopic sites.
FAU - Halaban, R
AU  - Halaban R
AD  - Department of Dermatology, Yale University School of Medicine, New Haven, 
      Connecticut 06510.
FAU - Rubin, J S
AU  - Rubin JS
FAU - Funasaka, Y
AU  - Funasaka Y
FAU - Cobb, M
AU  - Cobb M
FAU - Boulton, T
AU  - Boulton T
FAU - Faletto, D
AU  - Faletto D
FAU - Rosen, E
AU  - Rosen E
FAU - Chan, A
AU  - Chan A
FAU - Yoko, K
AU  - Yoko K
FAU - White, W
AU  - White W
AU  - et al.
LA  - eng
GR  - 1RO1-AR39848/AR/NIAMS NIH HHS/United States
GR  - 5-R29-CA44542/CA/NCI NIH HHS/United States
GR  - DK 34128/DK/NIDDK NIH HHS/United States
PT  - Journal Article
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - England
TA  - Oncogene
JT  - Oncogene
JID - 8711562
RN  - 0 (MAS1 protein, human)
RN  - 0 (Proto-Oncogene Mas)
RN  - 0 (Proto-Oncogene Proteins)
RN  - 42HK56048U (Tyrosine)
RN  - 63X7MBT2LQ (Bucladesine)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 9007-49-2 (DNA)
RN  - EC 2.7.- (Protein Kinases)
RN  - EC 2.7.10.1 (Proto-Oncogene Proteins c-met)
RN  - EC 2.7.11.17 (Calcium-Calmodulin-Dependent Protein Kinases)
SB  - IM
MH  - Animals
MH  - Bucladesine/pharmacology
MH  - Calcium-Calmodulin-Dependent Protein Kinases
MH  - Cells, Cultured
MH  - DNA/analysis
MH  - Hepatocyte Growth Factor/genetics/*pharmacology
MH  - Humans
MH  - Melanocytes/*drug effects/metabolism
MH  - Melanoma/metabolism/*pathology
MH  - Mice
MH  - Phosphorylation
MH  - Protein Kinases/analysis
MH  - Proto-Oncogene Mas
MH  - Proto-Oncogene Proteins/metabolism/*pharmacology
MH  - Proto-Oncogene Proteins c-met
MH  - Signal Transduction/*drug effects
MH  - Tyrosine/metabolism
EDAT- 1992/11/01 00:00
MHDA- 1992/11/01 00:01
CRDT- 1992/11/01 00:00
PHST- 1992/11/01 00:00 [pubmed]
PHST- 1992/11/01 00:01 [medline]
PHST- 1992/11/01 00:00 [entrez]
PST - ppublish
SO  - Oncogene. 1992 Nov;7(11):2195-206.