| First Author | Jesenberger V | Year | 2001 |
| Journal | J Exp Med | Volume | 193 |
| Issue | 3 | Pages | 353-64 |
| PubMed ID | 11157055 | Mgi Jnum | J:93687 |
| Mgi Id | MGI:3497906 | Doi | 10.1084/jem.193.3.353 |
| Citation | Jesenberger V, et al. (2001) Protective role of Raf-1 in Salmonella-induced macrophage apoptosis. J Exp Med 193(3):353-64 |
| abstractText | Invasive Salmonella induces macrophage apoptosis via the activation of caspase-1 by the bacterial protein SipB. Here we show that infection of macrophages with Salmonella causes the activation and degradation of Raf-1, an important intermediate in macrophage proliferation and activation. Raf-1 degradation is SipB- and caspase-1-dependent, and is prevented by proteasome inhibitors. To study the functional significance of Raf-1 in this process, the c-raf-1 gene was inactivated by Cre-loxP-mediated recombination in vivo. Macrophages lacking c-raf-1 are hypersensitive towards pathogen-induced apoptosis. Surprisingly, activation of the antiapoptotic mitogen-activated protein kinase kinase (MEK)/extracellular signal-regulated kinase (ERK) and nuclear factor kappaB pathways is normal in Raf-1-deficient macrophages, and mitochondrial fragility is not increased. Instead, pathogen-mediated activation of caspase-1 is enhanced selectively, implying that Raf-1 antagonizes stimulus-induced caspase-1 activation and apoptosis. |
