Increased focal adhesion kinase- and urokinase-type plasminogen activator receptor-associated cell signaling in endothelial cells exposed to asbestos
| Autor: | L C Elmore, M D Treadwell, Aaron Barchowsky, B.M. Lannon |
|---|---|
| Rok vydání: | 1997 |
| Předmět: |
Swine
Health Toxicology and Mutagenesis PTK2 Receptor tyrosine kinase Focal adhesion Plasminogen Activator Inhibitor 1 Chrysotile Cell Adhesion Plasminogen Activator Inhibitor 2 Animals Endothelium biology Public Health Environmental and Occupational Health Asbestos Protein-Tyrosine Kinases Precipitin Tests Molecular biology Urokinase receptor src-Family Kinases Gene Expression Regulation Carcinogens biology.protein Signal transduction Tyrosine kinase Signal Transduction Research Article Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Environmental Health Perspectives |
| ISSN: | 1552-9924 0091-6765 |
| Popis: | Exposure of low-passage endothelial cells in culture to nonlethal amounts of asbestos, but not refractory ceramic fiber-1, increases cell motility and gene expression. These changes may be initiated by the fibers mimicking matrix proteins as ligands for receptors on the cell surface. In the present study, 1- to 3-hr exposures of endothelial cells to 5 mg/cm2 of chrysotile asbestos caused marked cell elongation and motility. However, little morphological change was seen when chrysotile was added to cells pretreated with either mannosamine to prevent assembly of glycophosphatidylinositol (GPI)-anchored receptors or with herbimycin A to inhibit tyrosine kinase activity. Affinity purification of GPI-anchored urokinase-type plasminogen activator receptor (uPAR) from chrysotile-exposed cells demonstrated that asbestos altered the profile of proteins and phosphoproteins complexed with this receptor. Tyrosine kinase activities in the complexes were also increased by asbestos. Immunoprecipitations with selective monoclonal antibodies demonstrated that both chrysotile and crocidolite asbestos increase kinase activities associated with p60 Src or p120 focal adhesion kinase (FAK). Further, chrysotile also changed the profile of proteins and phosphoproteins associated with FAK in intact cells. These data suggest that asbestos initiates endothelial cell phenotypic change through interactions with uPAR-containing complexes and that this change is mediated through tyrosine kinase cascades. Images Figure 1. A Figure 1. B Figure 1. C Figure 1. D Figure 1. E Figure 1. F Figure 1. G Figure 1. H Figure 2. A Figure 2. B Figure 3. A Figure 3. B Figure 3. C Figure 3. D |
| Databáze: | OpenAIRE |
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