Inactive BRAF mutants bind mutant RAS:GTP

Stable Identifier
R-HSA-6802937
Type
Reaction
Species
Homo sapiens
Compartment
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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
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
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, Belvin, M, Stokoe, D, Ludlam, MJ, Alvarado, R, Morales, T, Jaiswal, BS, Seshagiri, S, Aliagas, I, Sideris, S, Malek, S, Koeppen, H, Gloor, SL, Vigers, G, Brandhuber, BJ, Liu, B, Yen, I, Friedman, LS, Anderson, DJ, Hoeflich, KP, Song, K

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

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

Cell 2010
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
20179705 RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF

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

Nature 2010
Participants
Participates
This event is regulated
Positively by
Normal reaction
Functional status

Gain of function of genetically or chemically inactive BRAF [cytosol]

Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created
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