Moderate kinase activity BRAF mutants bind RAS:GTP

Stable Identifier
R-HSA-6802915
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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In addition to the prevalent and highly activating V600E mutation, a large number of rare, moderately activating BRAF mutations are also found in human cancers (Wan et al, 2004; Davies et al, 2002). Unlike the V600E mutant, these forms of BRAF require both RAS binding and dimerization to activate MAPK/ERK signaling (Wan et al, 2004; Freeman et al, 2013; reviewed in Lavoie and Therrien, 2015).

Literature References
PubMed ID Title Journal Year
12068308 Mutations of the BRAF gene in human cancer

Davies, H, Bignell, GR, Cox, C, Stephens, P, Edkins, S, Clegg, S, Teague, J, Woffendin, H, Garnett, MJ, Bottomley, W, Davis, N, Dicks, E, Ewing, R, Floyd, Y, Gray, K, Hall, S, Hawes, R, Hughes, J, Kosmidou, V, Menzies, A, Mould, C, Parker, A, Stevens, C, Watt, S, Hooper, S, Wilson, R, Jayatilake, H, Gusterson, BA, Cooper, C, Shipley, J, Hargrave, D, Pritchard-Jones, K, Maitland, N, Chenevix-Trench, G, Riggins, GJ, Bigner, DD, Palmieri, G, Cossu, A, Flanagan, A, Nicholson, A, Ho, JW, Leung, SY, Yuen, ST, Weber, BL, Seigler, HF, Darrow, TL, Paterson, H, Marais, R, Marshall, CJ, Wooster, R, Stratton, MR, Futreal, PA

Nature 2002
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
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
Participants
Participant Of
This event is regulated
Positively by
Normal reaction
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created