Loading...
Please wait, while we are loading the content...
Similar Documents
Toxoplasma gondii triggers Gi-dependent PI 3-kinase signaling required for inhibition of host cell apoptosis.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Kim, Leesun |
| Copyright Year | 2006 |
| Abstract | Infection with the intracellular parasite Toxoplasma gondii renders cells resistant to multiple pro-apoptotic signals, but underlying mechanisms have not been delineated. The phosphoinositide 3-kinase (PI 3-kinase) pathway and the immediate downstream effector protein kinase B (PKB/Akt) play important roles in cell survival and apoptosis inhibition. Here, we show that Toxoplasma infection of mouse macrophages activates PKB/Akt in vivo and in vitro. In a mixed population of infected and non-infected macrophages, activation is only observed in parasite-infected cells. The PI 3-kinase inhibitors wortmannin and LY294002 block parasite-induced PKB phosphorylation. PKB activation occurs independently of Toll-like receptor adaptor protein MyD88 but uncoupling of Gi-protein-mediated signaling with pertussis toxin prevents PKB phosphorylation. Moreover, in the presence of PI 3-kinase inhibitors or pertussis toxin, not only PKB activation but also ERK1/2 activation during T. gondii infection is defective. Most importantly, the parasite's ability to induce macrophage resistance to pro-apoptotic signaling is prevented by incubation with PI 3-kinase inhibitors. This study demonstrates that T. gondii exploits host Gi-protein-dependent PI 3-kinase signaling to prevent induction of apoptosis in infected macrophages. |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | http://jcs.biologists.org/content/joces/119/10/2119.full.pdf |
| PubMed reference number | 16638808v1 |
| Volume Number | 119 |
| Part | 10 |
| Journal | Journal of cell science |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Adaptor Proteins, Signal Transducing Atrioventricular Block Cell Survival IGF2R protein, human Isoelectric Point LY 294002 Negative Regulation of Apoptosis Pertussis Toxin Phosphatidylinositols Positive Regulation of Apoptosis Precipitating Factors Protein Kinases Proto-Oncogene Proteins c-akt RAC-Alpha Serine/Threonine Kinase TLR4 protein, human Toxoplasma gondii apoptotic signaling pathway wortmannin |
| Content Type | Text |
| Resource Type | Article |
