The tyrosine kinase receptors ron and sea control "Scattering" and morphogenesis of liver progenitor cells in vitro

Enzo Medico, Adriana M. Mongiovi, Janice Huff, Mary Anne Jelinek, Antonia Follenzi, Giovanni Gaudino, J. Thomas Parsons, Paolo M. Comoglio

Research output: Contribution to journalArticlepeer-review

Abstract

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.

Original languageEnglish
Pages (from-to)495-504
Number of pages10
JournalMolecular Biology of the Cell
Volume7
Issue number4
Publication statusPublished - Apr 1996

ASJC Scopus subject areas

  • Cell Biology
  • Genetics
  • Molecular Biology

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