Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants

Stable Identifier
R-HSA-6802918
Type
Reaction [transition]
Species
Homo sapiens
Compartment
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Downstream of kinase-dead or inhibited forms of BRAF, activated MAP2K phosphorylates MAPK on threonine and tyrosine residues in the activation loop (Wan et al, 2004; Garnett et al, 2005; Heidorn et al, 2010; Poulikakos et al, 2010; Hatzivassilliou et al, 2010; reviewed in Samatar and Poulikakos, 2014; Lavoie and Therrien, 2015).

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
Participants
Participant Of
Catalyst Activity
Catalyst Activity
Title
protein serine/threonine/tyrosine kinase activity of RAS:GTP: inactive p-RAF:p-2S MAP2Ks:MAPKs:scaffold proteins [plasma membrane]
Physical Entity
Activity
Normal reaction
Disease
Name Identifier Synonyms
cancer 162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created