PMID- 8043510
OWN - NLM
STAT- MEDLINE
DCOM- 19940831
LR  - 20091119
IS  - 1044-9523 (Print)
IS  - 1044-9523 (Linking)
VI  - 5
IP  - 4
DP  - 1994 Apr
TI  - Receptor chimeras indicate that the met tyrosine kinase mediates the motility and 
      morphogenic responses of hepatocyte growth/scatter factor.
PG  - 359-66
AB  - The met protooncogene is a receptor tyrosine kinase for hepatocyte growth 
      factor/scatter factor (HGF/SF). HGF/SF is a multifunctional cytokine secreted 
      mainly by mesenchymal cells that stimulates movement, invasion, and morphogenesis 
      of some epithelial and endothelial cells and mitogenicity of others. Although the 
      met receptor tyrosine kinase is a high affinity receptor for HGF/SF, it is not 
      known whether this receptor can mediate the pleiotropic functions of HGF/SF. To 
      investigate this in epithelial cells that normally respond to HGF/SF, we 
      generated a chimeric receptor containing the extracellular domain from the colony 
      stimulating factor 1 (CSF-1) receptor fused to the transmembrane and cytoplasmic 
      domain of the met receptor. We show that the CSF-MET chimera, when expressed in 
      Madin-Darby canine kidney (MDCK) epithelial cells, is fully functional. Treatment 
      of MDCK cells expressing the chimera with CSF-1 leads to cell dissociation and 
      scattering, as well as invasion and tubule formation of cells grown in collagen 
      matrices. This effect is dependent on a functional met kinase. Stimulation of the 
      receptor chimera with CSF-1 leads to activation of the met kinase and tyrosine 
      phosphorylation of the chimeras in vivo, whereas a kinase inactive mutant chimera 
      shows no biological response to CSF-1. These findings demonstrate that 
      stimulation of the met kinase is sufficient and essential to mediate the 
      motogenic, invasive, and morphogenic responses of MDCK cells to HGF/SF and that 
      this is a suitable system for a detailed analysis of the molecular signaling 
      events involved in these responses.
FAU - Zhu, H
AU  - Zhu H
AD  - Molecular Oncology Group, Royal Victoria Hospital, Montreal, Quebec, Canada.
FAU - Naujokas, M A
AU  - Naujokas MA
FAU - Park, M
AU  - Park M
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - Cell Growth Differ
JT  - Cell growth & differentiation : the molecular biology journal of the American 
      Association for Cancer Research
JID - 9100024
RN  - 0 (Recombinant Fusion Proteins)
RN  - 67256-21-7 (Hepatocyte Growth Factor)
RN  - 81627-83-0 (Macrophage Colony-Stimulating Factor)
RN  - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases)
SB  - IM
GS  - met
MH  - Amino Acid Sequence
MH  - Animals
MH  - Base Sequence
MH  - Cell Line
MH  - Cell Movement/physiology
MH  - Dogs
MH  - Epithelial Cells
MH  - Epithelium/physiology
MH  - Hepatocyte Growth Factor/*physiology
MH  - Humans
MH  - Kidney/cytology/*physiology
MH  - Kidney Tubules/physiology
MH  - Macrophage Colony-Stimulating Factor/genetics
MH  - Molecular Sequence Data
MH  - Morphogenesis/physiology
MH  - Phosphorylation
MH  - Receptor Protein-Tyrosine Kinases/genetics/*physiology
MH  - Recombinant Fusion Proteins/genetics/*physiology
MH  - Signal Transduction/genetics
EDAT- 1994/04/01 00:00
MHDA- 1994/04/01 00:01
CRDT- 1994/04/01 00:00
PHST- 1994/04/01 00:00 [pubmed]
PHST- 1994/04/01 00:01 [medline]
PHST- 1994/04/01 00:00 [entrez]
PST - ppublish
SO  - Cell Growth Differ. 1994 Apr;5(4):359-66.