Inactive BRAF mutants:mutant RAS:GTP bind RAF1

Stable Identifier
Reaction [binding]
Homo sapiens
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The paradoxical activation of ERK signaling downstream of kinase-dead or inhibited forms of BRAF appears to result from enhanced dimerization with RAF1/CRAF (Wan et al, 2004; Poulikakos et al, 2010; Heidorn et al, 2010; Hatzivassilliou et al, 2010; Freeman et al, 2013). The propensity to dimerize may be promoted by conformational changes in the BRAF monomer as a result of mutation or inhibitor binding (reviewed in Samatar and Poulikakos, 2014; Lavoie and Therrien, 2015).

Literature References
PubMed ID Title Journal Year
22510884 Distinct requirement for an intact dimer interface in wild-type, V600E and kinase-dead B-Raf signalling

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

EMBO J. 2012
25907612 Regulation of RAF protein kinases in ERK signalling

Lavoie, H, Therrien, M

Nat. Rev. Mol. Cell Biol. 2015
23352452 Effects of Raf dimerization and its inhibition on normal and disease-associated Raf signaling

Freeman, AK, Ritt, DA, Morrison, DK

Mol. Cell 2013
20130576 RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth

Hatzivassiliou, G, Song, K, Yen, I, Brandhuber, BJ, Anderson, DJ, Alvarado, R, Ludlam, MJ, Stokoe, D, Gloor, SL, Vigers, G, Morales, T, Aliagas, I, Liu, B, Sideris, S, Hoeflich, KP, Jaiswal, BS, Seshagiri, S, Koeppen, H, Belvin, M, Friedman, LS, Malek, S

Nature 2010
20141835 Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF

Heidorn, SJ, Milagre, C, Whittaker, S, Nourry, A, Niculescu-Duvas, I, Dhomen, N, Hussain, J, Reis-Filho, JS, Springer, CJ, Pritchard, C, Marais, R

Cell 2010
25435214 Targeting RAS-ERK signalling in cancer: promises and challenges

Samatar, AA, Poulikakos, PI

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

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

Cell 2004
20179705 RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF

Poulikakos, PI, Zhang, C, Bollag, G, Shokat, KM, Rosen, N

Nature 2010
Participant Of
This event is regulated
Positively by
Normal reaction
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
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