Reactome | Homo- or heterodimerization of RAF downstream of mutant RAS

Homo- or heterodimerization of RAF downstream of mutant RAS

Stable Identifier

R-HSA-6803240

Type

Reaction [omitted]

Species

Homo sapiens

Compartment

plasma membrane

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Homo- or heterodimerization of RAF downstream of mutant RAS

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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