RAF is phosphorylated downstream of moderate kinase activity BRAF mutants

Stable Identifier
Reaction [transition]
Homo sapiens
Locations in the PathwayBrowser
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Homo- or heterodimerization (with RAF1, also known as CRAF) downstream of moderate kinase activity BRAF mutants leads to phosphorylation and activation of the 'receiver' kinase. Unlike the case for the highly active V600E BRAF mutation, pathway activation downstream of moderately activated BRAF mutants depends both on RAS binding and on dimerization (Wan et al, 2004; Roring et al, 2012; Freeman et al, 2013; reviewed in Samatar and Poulikakos, 2014; Lavoie and Therrien, 2015)

Literature References
PubMed ID Title Journal Year
25907612 Regulation of RAF protein kinases in ERK signalling

Lavoie, H, Therrien, M

Nat. Rev. Mol. Cell Biol. 2015
22510884 Distinct requirement for an intact dimer interface in wild-type, V600E and kinase-dead B-Raf signalling

Fiala, GJ, Herr, R, Röring, M, Heilmann, K, Schamel, WW, Saunders, DN, Halbach, S, Capper, D, Brummer, T, Braun, S, von Deimling, A, Eisenhardt, AE

EMBO J. 2012
25435214 Targeting RAS-ERK signalling in cancer: promises and challenges

Poulikakos, PI, Samatar, AA

Nat Rev Drug Discov 2014
15035987 Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF

Niculescu-Duvaz, D, Lee, S, Marais, R, Marshall, CJ, Barford, D, Jones, CM, Good, VM, Springer, CJ, Wan, PT, Garnett, MJ, Roe, SM

Cell 2004
19933846 Impact of feedback phosphorylation and Raf heterodimerization on normal and mutant B-Raf signaling

Specht, SI, Monson, DM, Morrison, DK, Ritt, DA

Mol. Cell. Biol. 2010
Catalyst Activity

protein serine/threonine/tyrosine kinase activity of RAF activating kinases [plasma membrane]

Normal reaction
Functional status

Gain of function of RAS:GTP:moderate kinase activity BRAF mutants:RAF:YWHAB [plasma membrane]

Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
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