Inactive BRAF mutants:mutant RAS:GTP bind RAF1

Stable Identifier
R-HSA-8936731
Type
Reaction [binding]
Species
Homo sapiens
Compartment
plasma membrane
ReviewStatus
5/5
Locations in the PathwayBrowser
Expand all
General
SVG | 
PNG
Low
Medium
High
 | PPTX  | SBGN
Inactive BRAF mutants:mutant RAS:GTP bind RAF1
Click the image above or here to open this reaction in the Pathway Browser
The layout of this reaction may differ from that in the pathway view due to the constraints in pathway layout
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
Input
Output
Participates
as an event of
This event is regulated
Negatively by
Regulator
BRAP:KSR1:MARK3 [cytosol] (Homo sapiens)
Positively by
Regulator
MAP3K11 [cytosol] (Homo sapiens)
Normal reaction
RAS:GTP:'activator' RAF homo/heterodimerizes with other RAF monomers (Homo sapiens)
Functional status

Gain of function of chemically or genetically inactive BRAF mutants:mutant RAS:GTP [plasma membrane]

Normal Entity
Disease Entity
Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Rothfels, K  (2015-05-18)
Reviewed
Stephens, RM  (2016-08-05)
Created
Rothfels, K  (2016-08-23)
Cite Us!