| Autor: |
Vincent TS; Departments of Pathology and Laboratory Medicine, Medical University of South Carolina, Charleston 29425, USA. vincents@musc.edu, Fraylick JE, McGuffie EM, Olson JC |
| Jazyk: |
angličtina |
| Zdroj: |
Molecular microbiology [Mol Microbiol] 1999 Jun; Vol. 32 (5), pp. 1054-64. |
| DOI: |
10.1046/j.1365-2958.1999.01420.x |
| Abstrakt: |
The exoenzyme S (ExoS)-producing Pseudomonas aeruginosa strain, 388, and corresponding ExoS knock-out strain, 388deltaexoS, were used in a bacterial and mammalian co-culture system as a model for the contact-dependent delivery of ExoS into host cells. Examination of DNA synthesis and Ras ADP-ribosylation in tumour cell lines expressing normal and mutant Ras revealed a decrease in DNA synthesis concomitant with ADP-ribosylation of Ras proteins after exposure to ExoS-producing bacteria, but not after exposure to non-ExoS-producing bacteria. Examination of normal H-Ras, K-Ras and N-Ras by two-dimensional electrophoresis after exposure to bacteria revealed differences in the degree of ADP-ribosylation by ExoS, with H-Ras being modified most extensively. ADP-ribosylation of oncogenic forms of Ras was examined in vivo using cancer lines expressing mutant forms of H-, N- or K-Ras. The mutant Ras proteins were modified in a manner qualitatively similar to their normal counterparts. Using Ras/Raf-1 co-immunoprecipitation after co-culture, it was found that exposure to ExoS-producing bacteria caused a decrease in the amount of Raf-1 associated with EGF-activated Ras and oncogenic Ras. The results from this study indicate that ExoS ADP-ribosylates both normal and mutant Ras proteins in vivo and inhibits signalling through Ras. |
| Databáze: |
MEDLINE |
| Externí odkaz: |
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