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1.
Previously, we demonstrated that Pseudomonas aeruginosa ExoT induces potent apoptosis in host epithelial cells in a manner that primarily depends on its ADP-ribosyltransferase domain (ADPRT) activity. However, the mechanism underlying ExoT/ADPRT-induced apoptosis remains undetermined. We now report that ExoT/ADPRT disrupts focal adhesion sites, activates p38β and JNK, and interferes with integrin-mediated survival signaling; causing atypical anoikis. We show that ExoT/ADPRT-induced anoikis is mediated by the Crk adaptor protein. We found that Crk-/- knockout cells are significantly more resistant to ExoT-induced apoptosis, while Crk-/- cells complemented with Crk are rendered sensitive to ExoT-induced apoptosis. Moreover, a dominant negative (DN) mutant form of Crk phenocopies ExoT-induced apoptosis both kinetically and mechanistically. Crk is generally believed to be a component of focal adhesion (FA) and its role in cellular survival remains controversial in that it has been found to be either pro-survival or pro-apoptosis. Our data demonstrate that although Crk is recruited to FA sites, its function is likely not required for FA assembly or for survival per se. However, when modified by ExoT or by mutagenesis, it can be transformed into a cytotoxin that induces anoikis by disrupting FA sites and interfering with integrin survival signaling. To our knowledge, this is the first example whereby a bacterial toxin exerts its cytotoxicity by subverting the function of an innocuous host cellular protein and turning it against the host cell. 相似文献
2.
Dr. Josef Murr 《Plant Systematics and Evolution》1888,38(7):237-240
Ohne Zusammenfassung 相似文献
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Domination among strategies in an evolutionary game implies that the geometric mean of the frequencies of certain strategies—the unfit—approaches zero. However, as we show by example no one strategy need be eliminated in the limit. 相似文献
5.
Josef Kisser 《Plant Systematics and Evolution》1925,74(4-6):115-122
Ohne Zusammenfassung 相似文献
6.
Josef Ullepitsch 《Plant Systematics and Evolution》1886,36(12):399-400
Ohne Zusammenfassung 相似文献
7.
Ingenieur Josef Schorstein 《Plant Systematics and Evolution》1910,60(3):112-114
Ohne Zusammenfassung 相似文献
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9.
Heinr Frh v. Handel-Mazzetti Josef Stadlmann Erwin Janchen Franz Faltis 《Plant Systematics and Evolution》1905,55(11):424-438
Ohne Zusammenfassung 相似文献
10.
Hermann-Josef Egger Josef Reiner Gerhard Spiteller 《Journal of chromatography. B, Analytical technologies in the biomedical and life sciences》1978,145(3):359-369
Urine steroid profiles of hirsute womenSteroid profiles of women suffering from idiopathic hirsutism show in more than 50% of the cases a 10–100 fold increase in the excretion of dehydroepiandrosterone (DHEA) compared with normal values.The excretion of DHEA was reduced much more than that of other 17-ketosteroids if the adrenals (NNR) were suppressed by dexamethasone (DXM). Within one week they reached values at the compound noise level of the gas chromatograms. If the ovaries were stimulated with human chorionic gonadotropin during continued suppression of the NNR with DXM no increase of DHEA could be detected. 相似文献