PMID- 9101091 OWN - NLM STAT- MEDLINE DCOM- 19970815 LR - 20091119 IS - 1044-9523 (Print) IS - 1044-9523 (Linking) VI - 8 IP - 4 DP - 1997 Apr TI - Inhibition of junction assembly in cultured epithelial cells by hepatocyte growth factor/scatter factor is concomitant with increased stability and altered phosphorylation of the soluble junctional molecules. PG - 451-62 AB - Hepatocyte growth factor/scatter factor (HGF/SF) is a mesenchymally derived glycoprotein with a strong scattering effect on epithelial cells. A receptor tyrosine kinase encoded by the met proto-oncogene has been identified as the cellular receptor for HGF/SF. Following stimulation with HGF/SF, cell scattering occurs concurrent with decreased cell-cell adhesion and disassembly of junctional components. In culture, junction formation is cell-cell contact dependent and can be regulated by modulating the Ca2+ concentrations of the growth media. Decreasing the Ca2+ concentrations below 50 microM causes rapid disassembly of junctions, whereas increasing the Ca2+ concentrations to 1.8 mM induces cell-cell contact and junction assembly. Although associated with decreased cell-cell adhesion and disassembly of the junctional complex, HGF/SF-induced scattering occurs under high extracellular Ca2+ concentrations. To gain insight into the mechanisms of HGF/SF-induced scattering of epithelial cells, we have studied the effect(s) of HGF/SF on junction assembly by examining the solubility, stability, phosphorylation, and subcellular localization of the major components of the adhering junctions, plakoglobin (Pg) and E-cadherin, in Madin-Darby canine kidney (MDCK) epithelial cells and in a MDCK cell line expressing an exogenous chimeric met receptor (CSF-MET) that scatters in response to colony-stimulating factor 1 (CSF-1). The results have shown that in HGF/SF-stimulated MDCK cells, adhering junctions were not assembled upon induction of cell-cell contact. Immunofluorescence analyses showed that larger amounts of Pg and E-cadherin were Triton X-100 extractable, and more significantly, these proteins were homogeneously distributed along the membrane and were not concentrated at the areas of cell-cell contact. Similar results were obtained for CSF-MET expressing MDCK cells in response to CSF-1. In contrast, none of the above effects were detected in MDCK cells expressing a mutant CSF-MET chimera containing a phenylalanine substitution at tyrosine 1356 in met, which fails to scatter in response to CSF-1. When compared with the unstimulated cells, the inhibition of cell adhesion promoted by HGF/SF correlated with an increased stability of the newly synthesized soluble E-cadherin and Pg and an altered phosphorylation pattern of E-cadherin, as determined by partial proteolytic peptide mapping. FAU - Pasdar, M AU - Pasdar M AD - Department of Anatomy and Cell Biology, University of Alberta, Edmonton, Canada. mpasdar@anat.med.ualberta.ca FAU - Li, Z AU - Li Z FAU - Marreli, M AU - Marreli M FAU - Nguyen, B T AU - Nguyen BT FAU - Park, M AU - Park M FAU - Wong, K AU - Wong K 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 (Cadherins) RN - 0 (Cell Adhesion Molecules) RN - 0 (Colony-Stimulating Factors) RN - 0 (Cytoskeletal Proteins) RN - 0 (Desmoplakins) RN - 0 (Proto-Oncogene Proteins) RN - 0 (Recombinant Fusion Proteins) RN - 0 (gamma Catenin) RN - 67256-21-7 (Hepatocyte Growth Factor) RN - 81627-83-0 (Macrophage Colony-Stimulating Factor) RN - EC 2.7.10.1 (Proto-Oncogene Proteins c-met) RN - EC 2.7.10.1 (Receptor Protein-Tyrosine Kinases) SB - IM MH - Animals MH - Cadherins/metabolism MH - Cell Adhesion/drug effects MH - Cell Adhesion Molecules/metabolism MH - Colony-Stimulating Factors/genetics/metabolism MH - Cytoskeletal Proteins/metabolism MH - Desmoplakins MH - Desmosomes/metabolism MH - Dogs MH - Epithelial Cells MH - Epithelium/drug effects MH - Hepatocyte Growth Factor/*pharmacology MH - Intercellular Junctions/*drug effects MH - Macrophage Colony-Stimulating Factor/metabolism MH - Phosphorylation MH - Proto-Oncogene Proteins/genetics/metabolism MH - Proto-Oncogene Proteins c-met MH - Receptor Protein-Tyrosine Kinases/genetics/metabolism MH - Recombinant Fusion Proteins/metabolism MH - gamma Catenin EDAT- 1997/04/01 00:00 MHDA- 1997/04/01 00:01 CRDT- 1997/04/01 00:00 PHST- 1997/04/01 00:00 [pubmed] PHST- 1997/04/01 00:01 [medline] PHST- 1997/04/01 00:00 [entrez] PST - ppublish SO - Cell Growth Differ. 1997 Apr;8(4):451-62.