| First Author | Hüser M | Year | 2001 |
| Journal | EMBO J | Volume | 20 |
| Issue | 8 | Pages | 1940-51 |
| PubMed ID | 11296227 | Mgi Jnum | J:89619 |
| Mgi Id | MGI:3040858 | Doi | 10.1093/emboj/20.8.1940 |
| Citation | Huser M, et al. (2001) MEK kinase activity is not necessary for Raf-1 function. EMBO J 20(8):1940-51 |
| abstractText | Raf-1 protein kinase has been identified as an integral component of the Ras/Raf/MEK/ERK signalling pathway in mammals. Activation of Raf-1 is achieved by RAS:GTP binding and other events at the plasma membrane including tyrosine phosphorylation at residues 340/341. We have used gene targeting to generate a 'knockout' of the raf-1 gene in mice as well as a rafFF mutant version of endogenous Raf-1 with Y340FY341F mutations. Raf-1(-/-) mice die in embryogenesis and show vascular defects in the yolk sac and placenta as well as increased apoptosis of embryonic tissues. Cell proliferation is not affected. Raf-1 from cells derived from raf-1(FF/FF) mice has no detectable activity towards MEK in vitro, and yet raf-1(FF/FF) mice survive to adulthood, are fertile and have an apparently normal phenotype. In cells derived from both the raf-1(-/-) and raf-1(FF/FF) mice, ERK activation is normal. These results strongly argue that MEK kinase activity of Raf-1 is not essential for normal mouse development and that Raf-1 plays a key role in preventing apoptosis. |
