RAS:GTP:p-RAF complexes paradoxically bind MAP2Ks and MAPKs

Stable Identifier
R-HSA-6802942
Type
Reaction [binding]
Species
Homo sapiens
Compartment
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Dimerization of kinase-dead or inhibited versions of BRAF to RAF1/CRAF leads to the recruitment and phosphorylation of MAP2Ks and MAPKs (Wan et al, 2004; Garnett et al, 2005; Heidorn et al, 2010; Poulikakos et al, 2010; Hatzivassiliou et al, 2010; reviewed in Samatar and Poulikakos, 2014; Lavoie and Therrien, 2015). Although the interactions haven't been studied in detail, these disease pathways are presumed to recruit MAP2Ks and MAPKs in a scaffold-dependent manner similar to WT (reviewed in Matallanas et al, 2011).

Literature References
PubMed ID Title Journal Year
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
25907612 Regulation of RAF protein kinases in ERK signalling

Lavoie, H, Therrien, M

Nat. Rev. Mol. Cell Biol. 2015
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
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
25435214 Targeting RAS-ERK signalling in cancer: promises and challenges

Samatar, AA, Poulikakos, PI

Nat Rev Drug Discov 2014
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
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
21779496 Raf family kinases: old dogs have learned new tricks

Matallanas, D, Birtwistle, M, Romano, D, Zebisch, A, Rauch, J, von Kriegsheim, A, Kolch, W

Genes Cancer 2011
Participants
Participant Of
This event is regulated
Normal reaction
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created