The tyrosine kinase receptors Ron and Sea control "scattering" and morphogenesis of liver progenitor cells in vitro.
The mammalian RON and the avian sea genes encode tyrosine kinase receptors of poorly characterized biological functions. We recently identified macrophage-stimulating protein as the ligand for Ron; no ligand has yet been found for Sea. In this work we investigated the biological response to macrophage-stimulating protein in mouse liver progenitor cells expressing Ron. These cells were also transfected with a chimeric cDNA encoding the cytoplasmic domain of Sea, fused to the extracellular domain of Trk (nerve growth factor receptor). In the presence of nanomolar concentrations of the respective ligands, both receptors induced cell "scattering", extracellular matrix invasion, and DNA synthesis. When liver progenitor cells were grown in a tri-dimensional type-I collagen matrix, ligand-induced stimulation of either Ron or Sea induced sprouting of branched cell cords, evolving into ductular-like tubules. The motogenic, mitogenic, and morphogenic responses were also elicited by triggering the structurally related hepatocyte growth factor receptor (Met) but not epidermal growth factor or platelet-derived growth factor receptors. These data show that Ron, Sea, and Met belong to a receptor subfamily that elicits a distinctive biological response in epithelial cells.
Medico
E
E
Institute for Cancer Research (I.R.C.C.), University of Torino School of Medicine, Italy.
Mongiovi
A M
AM
Huff
J
J
Jelinek
M A
MA
Follenzi
A
A
Gaudino
G
G
Parsons
J T
JT
Comoglio
P M
PM
D000595:Amino Acid Sequence; D000818:Animals; D030161:Avian Proteins; D001483:Base Sequence; D015153:Blotting, Western; D002454:Cell Differentiation / Q000502:physiology; D002478:Cells, Cultured; D006224:Cricetinae; D004261:DNA Replication; D066298:In Vitro Techniques; D008099:Liver / Q000166:cytology*; D051379:Mice; D008854:Microscopy, Electron; D008969:Molecular Sequence Data; D010641:Phenotype; D011505:Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D011518:Proto-Oncogene Proteins / Q000235:genetics; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics / Q000502:physiology*; D020917:Receptor, trkA; D011956:Receptors, Cell Surface / Q000235:genetics / Q000502:physiology*; D017475:Receptors, Nerve Growth Factor / Q000235:genetics; D011993:Recombinant Fusion Proteins / Q000235:genetics; D013234:Stem Cells / Q000166:cytology*; D014162:Transfection
D030161:Avian Proteins; D011518:Proto-Oncogene Proteins; D011956:Receptors, Cell Surface; D017475:Receptors, Nerve Growth Factor; D011993:Recombinant Fusion Proteins; C082018:sea protein, Gallus gallus; D011505:Protein-Tyrosine Kinases; C080835:RON protein; D020794:Receptor Protein-Tyrosine Kinases; D020917:Receptor, trkA