Homo- or heterodimerization of RAF downstream of mutant RAS

Stable Identifier
Reaction [omitted]
Homo sapiens
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Similar to the WT pathway, activation of RAF downstream of oncogenic RAS depends on homo- or heterodimerization of RAF, although the importance of RAF proteins varies among cancer types (Dumaz et al, 2006; Heidorn et al, 2010; Blasco et al, 2011; Karreth et al, 2011; Eser et al, 2013; Heidorn et al, 2010; Poulikakos et al, 2010; Hatzivassiliou et al, 2010; reviewed in Lito et al, 2013). A notable exception to this requirement for RAF dimerization is BRAF V600E, which is RAS-independent and constitutively active as a monomer (Roring et al, 2012; Brummer et al, 2006; Freeman et al, 2013; Garnett et al, 2005).

Literature References
PubMed ID Title Journal Year
21993244 RAS oncogenes: weaving a tumorigenic web

Pylayeva-Gupta, Y, Grabocka, E, Bar-Sagi, D

Nat. Rev. Cancer 2011
16702958 Functional analysis of the regulatory requirements of B-Raf and the B-Raf(V600E) oncoprotein

Brummer, T, Martin, P, Herzog, S, Misawa, Y, Daly, RJ, Reth, M

Oncogene 2006
21514245 c-Raf, but not B-Raf, is essential for development of K-Ras oncogene-driven non-small cell lung carcinoma

Blasco, RB, Francoz, S, Santamaría, D, Cañamero, M, Dubus, P, Charron, J, Baccarini, M, Barbacid, M

Cancer Cell 2011
16364920 Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization

Garnett, MJ, Rana, S, Paterson, H, Barford, D, Marais, R

Mol. Cell 2005
23352452 Effects of Raf dimerization and its inhibition on normal and disease-associated Raf signaling

Freeman, AK, Ritt, DA, Morrison, DK

Mol. Cell 2013
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
22589270 A comprehensive survey of Ras mutations in cancer

Prior, IA, Lewis, PD, Mattos, C

Cancer Res. 2012
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
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
22043453 C-Raf is required for the initiation of lung cancer by K-Ras(G12D)

Karreth, FA, Frese, KK, DeNicola, GM, Baccarini, M, Tuveson, DA

Cancer Discov 2011
17018604 In melanoma, RAS mutations are accompanied by switching signaling from BRAF to CRAF and disrupted cyclic AMP signaling

Dumaz, N, Hayward, R, Martin, J, Ogilvie, L, Hedley, D, Curtin, JA, Bastian, BC, Springer, C, Marais, R

Cancer Res. 2006
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
24202393 Tumor adaptation and resistance to RAF inhibitors

Lito, P, Rosen, N, Solit, DB

Nat. Med. 2013
23453624 Selective requirement of PI3K/PDK1 signaling for Kras oncogene-driven pancreatic cell plasticity and cancer

Eser, S, Reiff, N, Messer, M, Seidler, B, Gottschalk, K, Dobler, M, Hieber, M, Arbeiter, A, Klein, S, Kong, B, Michalski, CW, Schlitter, AM, Esposito, I, Kind, AJ, Rad, L, Schnieke, AE, Baccarini, M, Alessi, DR, Rad, R, Schmid, RM, Schneider, G, Saur, D

Cancer Cell 2013
Participant Of
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Normal reaction
Name Identifier Synonyms
Noonan syndrome 3490 Turner's phenotype, karyotype normal (disorder)
cancer 162 malignant tumor, malignant neoplasm, primary cancer
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