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MEK kinase activity is not necessary for Raf-1 function.

M Hüser·J Luckett·A Chiloeches·K Mercer·M Iwobi·S Giblett·X M Sun·J Brown·R Marais·C Pritchard
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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.

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AnimalsApoptosisCell DivisionEmbryo, MammalianGenes, EssentialGenotypeHeterozygoteHomozygoteMAP Kinase Kinase Kinase 1MiceMice, Inbred C57BLMice, KnockoutMutationPhenotypeProtein Serine-Threonine KinasesProto-Oncogene Proteins c-rafSignal TransductionYolk SacJournal ArticleResearch Support, Non-U.S. Gov't

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M Hüser, J Luckett, A Chiloeches, K Mercer, M Iwobi, S Giblett, X M Sun, J Brown, R Marais, C Pritchard. 2001-04-17. MEK kinase activity is not necessary for Raf-1 function.. https://doi.org/10.1093/emboj%2F20.8.1940

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