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The phosphoinositol-3-kinase-protein kinase B/Akt pathway is critical for Pseudomonas aeruginosa strain PAK internalization.
- Source :
-
Molecular biology of the cell [Mol Biol Cell] 2005 May; Vol. 16 (5), pp. 2577-85. Date of Electronic Publication: 2005 Mar 16. - Publication Year :
- 2005
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Abstract
- Several Pseudomonas aeruginosa strains are internalized by epithelial cells in vitro and in vivo, but the host pathways usurped by the bacteria to enter nonphagocytic cells are not clearly understood. Here, we report that internalization of strain PAK into epithelial cells triggers and requires activation of phosphatidylinositol 3-kinase (PI3K) and protein kinase B/Akt (Akt). Incubation of Madin-Darby canine kidney (MDCK) or HeLa cells with the PI3K inhibitors LY294002 (LY) or wortmannin abrogated PAK uptake. Addition of the PI3K product phosphatidylinositol 3,4,5-trisphosphate [PtdIns(3,4,5)P3] to polarized MDCK cells was sufficient to increase PAK internalization. PtdIns(3,4,5)P3 accumulated at the site of bacterial binding in an LY-dependent manner. Akt phosphorylation correlated with PAK invasion. The specific Akt phosphorylation inhibitor SH-5 inhibited PAK uptake; internalization also was inhibited by small interfering RNA-mediated depletion of Akt phosphorylation. Expression of constitutively active Akt was sufficient to restore invasion when PI3K signaling was inhibited. Together, these results demonstrate that the PI3K signaling pathway is necessary and sufficient for the P. aeruginosa entry and provide the first example of a bacterium that requires Akt for uptake into epithelial cells.
- Subjects :
- Animals
Cell Line
Dogs
Enzyme Activation
Epithelial Cells microbiology
HeLa Cells
Humans
Phosphatidylinositol Phosphates metabolism
Phosphatidylinositol Phosphates pharmacology
Protein Serine-Threonine Kinases antagonists & inhibitors
Protein Serine-Threonine Kinases genetics
Proto-Oncogene Proteins antagonists & inhibitors
Proto-Oncogene Proteins genetics
Proto-Oncogene Proteins c-akt
RNA, Small Interfering genetics
Signal Transduction
Phosphatidylinositol 3-Kinases metabolism
Protein Serine-Threonine Kinases metabolism
Proto-Oncogene Proteins metabolism
Pseudomonas aeruginosa metabolism
Pseudomonas aeruginosa pathogenicity
Subjects
Details
- Language :
- English
- ISSN :
- 1059-1524
- Volume :
- 16
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Molecular biology of the cell
- Publication Type :
- Academic Journal
- Accession number :
- 15772151
- Full Text :
- https://doi.org/10.1091/mbc.e04-08-0717