Premium
MEK kinase activity is not necessary for Raf‐1 function
Author(s) -
Hüser Martin,
Luckett Jeni,
Chiloeches Antonio,
Mercer Kathryn,
Iwobi Mabel,
Giblett Susan,
Sun XiaoMing,
Brown Jane,
Marais Richard,
Pritchard Catrin
Publication year - 2001
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/20.8.1940
Subject(s) - library science , computer science
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.