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- Title
MEK kinase activity is not necessary for Raf-1 function.
- Authors
Hüser, M; Luckett, J; Chiloeches, A; Mercer, K; Iwobi, M; Giblett, S; Sun, X M; Brown, J; Marais, R; Pritchard, C
- Abstract
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.
- Publication
The EMBO journal, 2001, Vol 20, Issue 8, p1940
- ISSN
0261-4189
- Publication type
Journal Article
- DOI
10.1093/emboj/20.8.1940