Enteropathogenic Escherichia coli use redundant tyrosine kinases to form actin pedestals Journal Article
| Authors: | Swimm, A.; Bommarius, B.; Li, Y.; Cheng, D.; Reeves, P.; Sherman, M.; Veach, D.; Bornmann, W.; Kalman, D. |
| Article Title: | Enteropathogenic Escherichia coli use redundant tyrosine kinases to form actin pedestals |
| Abstract: | Enteropathogenic Escherichia coli (EPEC) are deadly contaminants in water and food and induce protrusion of actin-rich membrane pedestals beneath themselves upon attachment to intestinal epithelia. EPEC then causes intestinal inflammation, diarrhea, and, among children, death. Here, we show that EPEC uses multiple tyrosine kinases for formation of pedestals, each of which is sufficient but not necessary. In particular, we show that Abl and Arg, members of the Abl family of tyrosine kinases, localize and are activated in pedestals. We also show that pyrido[2,3-d]pyrimidine (PD) compounds, which inhibit Abl, Arg, and related kinases, block pedestal formation. Finally, we show that Abl and Arg are sufficient for pedestal formation in the absence of other tyrosine kinase activity, but they are not necessary. Our results suggest that additional kinases that are sensitive to inhibition by PD also can suffice. Together, these results suggest that EPEC has evolved a mechanism to use any of several functionally redundant tyrosine kinases during pathogenesis, perhaps facilitating its capacity to infect different cell types. Moreover, PD compounds are being developed to treat cancers caused by dysregulated Abl. Our results raise the possibility that PD may be useful in treating EPEC infections, and because PD affects host and not bacterium, selecting resistant strains may be far less likely than with conventional antibiotics. |
| Keywords: | diarrhea; nonhuman; animal cell; mouse; animals; mice; actin; enzyme inhibition; cell line; nerve tissue proteins; enzyme activation; abelson kinase; protein tyrosine kinase; pyrimidines; phosphorylation; bacterial strain; bacteria (microorganisms); cell type; animalia; oncogene proteins; escherichia coli; enteritis; protein-tyrosine kinases; point mutation; protein family; actins; enzyme localization; escherichia coli proteins; host; wiskott-aldrich syndrome protein, neuronal; cytoskeletal proteins; receptors, cell surface; microfilaments; bacterium adherence; proto-oncogene proteins c-abl; intestine epithelium; negibacteria; escherichia coli infections; pyrido[2,3 d]pyrimidine derivative; priority journal; article; actin-related protein 2; actin-related protein 3 |
| Journal Title: | Molecular Biology of the Cell |
| Volume: | 15 |
| Issue: | 8 |
| ISSN: | 1059-1524 |
| Publisher: | The American Society for Cell Biology |
| Date Published: | 2004-08-01 |
| Start Page: | 3520 |
| End Page: | 3529 |
| Language: | English |
| DOI: | 10.1091/mbc.E04-02-0093 |
| PROVIDER: | scopus |
| PMCID: | PMC491815 |
| PUBMED: | 15155808 |
| DOI/URL: | |
| Notes: | Mol. Biol. Cell -- Cited By (since 1996):61 -- Export Date: 16 June 2014 -- CODEN: MBCEE -- Source: Scopus |
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