期刊
CELLULAR MICROBIOLOGY
卷 11, 期 12, 页码 1782-1801出版社
WILEY
DOI: 10.1111/j.1462-5822.2009.01371.x
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资金
- Deutsche Forschungsgemeinschaft [RTG 1121]
- Bundesministerium fur Bildung und Forschung [FBI-Zoo, 01 KI 07121]
- Fonds der Deutschen Chemie
The outer membrane proteins YadA and invasin of Yersinia pseudotuberculosis promote invasion into mammalian cells through beta(1)-integrins and trigger the production of interleukin (IL)-8. FAK, c-Src and the PI3 kinase were previously found to be important for both YadA-and invasin-promoted uptake. Here, we demonstrate that two different downstream effectors of PI3 kinase, Akt and phospholipase C gamma 1 are required for efficient cell invasion. Inhibition of Akt or phospholipase C-gamma (PLC-gamma)1 by pharmaceutical agents as well as reduced expression of the isoforms Akt1 and Akt2, and of PLC-gamma 1 by RNA interference decreased entry of YadA- and Inv-expressing bacteria significantly. In addition, we report that the conventional protein kinases C (PKC)alpha and -beta, positioned downstream of PLC-gamma 1, are activated upon Inv- or YadA-promoted cell entry. They colocalize with intracellular bacteria and their depletion by siRNA treatment also resulted in a strong reduction of cell entry. In contrast, neither Akt nor PLC-gamma 1, and the PKCs are essential for YadA-and Inv-mediated IL-8 synthesis and release. We conclude that YadA and invasin of Y. pseudotuberculosis both trigger similar signal transduction pathways during integrin-mediated phagocytosis into epithelial cells, which lead to the activation of Akt, PLC-gamma 1, PKC alpha and -beta downstream of PI3 kinase, separate from the MAPK-dependent pathway that triggers IL-8 production.
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