| First Author | Piazzolla D | Year | 2005 |
| Journal | J Cell Biol | Volume | 171 |
| Issue | 6 | Pages | 1013-22 |
| PubMed ID | 16365167 | Mgi Jnum | J:104536 |
| Mgi Id | MGI:3612236 | Doi | 10.1083/jcb.200504137 |
| Citation | Piazzolla D, et al. (2005) Raf-1 sets the threshold of Fas sensitivity by modulating Rok-{alpha} signaling. J Cell Biol 171(6):1013-22 |
| abstractText | Ablation of the Raf-1 protein causes fetal liver apoptosis, embryonic lethality, and selective hypersensitivity to Fas-induced cell death. Furthermore, Raf-1-deficient cells show defective migration as a result of the deregulation of the Rho effector kinase Rok-alpha. In this study, we show that the kinase-independent modulation of Rok-alpha signaling is also the basis of the antiapoptotic function of Raf-1. Fas activation stimulates the formation of Raf-1-Rok-alpha complexes, and Rok-alpha signaling is up-regulated in Raf-1-deficient cells. This leads to increased clustering and membrane expression of Fas, which is rescued both by kinase-dead Raf-1 and by interfering with Rok-alpha or its substrate ezrin. Increased Fas clustering and membrane expression are also evident in the livers of Raf-1-deficient embryos, and genetically reducing Fas expression counteracts fetal liver apoptosis, embryonic lethality, and the apoptotic defects of embryonic fibroblasts. Thus, Raf-1 has an essential function in regulating Fas expression and setting the threshold of Fas sensitivity during embryonic life. |
