| First Author | Ehrenreiter K | Year | 2005 |
| Journal | J Cell Biol | Volume | 168 |
| Issue | 6 | Pages | 955-64 |
| PubMed ID | 15753127 | Mgi Jnum | J:98083 |
| Mgi Id | MGI:3577128 | Doi | 10.1083/jcb.200409162 |
| Citation | Ehrenreiter K, et al. (2005) Raf-1 regulates Rho signaling and cell migration. J Cell Biol 168(6):955-64 |
| abstractText | Raf kinases relay signals inducing proliferation, differentiation, and survival. The Raf-1 isoform has been extensively studied as the upstream kinase linking Ras activation to the MEK/ERK module. Recently, however, genetic experiments have shown that Raf-1 plays an essential role in counteracting apoptosis, and that it does so independently of its ability to activate MEK. By conditional gene ablation, we now show that Raf-1 is required for normal wound healing in vivo and for the migration of keratinocytes and fibroblasts in vitro. Raf-1-deficient cells show a symmetric, contracted appearance, characterized by cortical actin bundles and by a disordered vimentin cytoskeleton. These defects are due to the hyperactivity and incorrect localization of the Rho-effector Rok-alpha to the plasma membrane. Raf-1 physically associates with Rok-alpha in wild-type (WT) cells, and reintroduction of either WT or kinase-dead Raf-1 in knockout fibroblasts rescues their defects in shape and migration. Thus, Raf-1 plays an essential, kinase-independent function as a spatial regulator of Rho downstream signaling during migration. |
