Cell invasion of Yersinia pseudotuberculosis by invasin and YadA requires protein kinase C, phospholipase C-γ1 and Akt kinase |
| |
Authors: | Frank Uliczka Tina Kornprobst Julia Eitel Daniela Schneider Petra Dersch |
| |
Affiliation: | Institut für Mikrobiologie, Technische Universität Braunschweig, 38106 Braunschweig, Germany.; Abteilung Molekulare Infektionsbiologie, Helmholtz-Zentrum für Infektionsforschung, 38124 Braunschweig, Germany. |
| |
Abstract: | The outer membrane proteins YadA and invasin of Yersinia pseudotuberculosis promote invasion into mammalian cells through β1-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 Cγ1 are required for efficient cell invasion. Inhibition of Akt or phospholipase C-γ (PLC-γ)1 by pharmaceutical agents as well as reduced expression of the isoforms Akt1 and Akt2, and of PLC-γ1 by RNA interference decreased entry of YadA- and Inv-expressing bacteria significantly. In addition, we report that the conventional protein kinases C (PKC)α and -β, positioned downstream of PLC-γ1, 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-γ1, 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-γ1, PKCα and -β downstream of PI3 kinase, separate from the MAPK-dependent pathway that triggers IL-8 production. |
| |
Keywords: | |
|
|