Activated MAP2Ks phosphorylate MAPKs downstream of inactive BRAF mutants

Stable Identifier
R-HSA-6802918
Type
Reaction [transition]
Species
Homo sapiens
Compartment
ReviewStatus
5/5
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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
25907612 Regulation of RAF protein kinases in ERK signalling

Lavoie, H, Therrien, M

Nat. Rev. Mol. Cell Biol. 2015
20130576 RAF inhibitors prime wild-type RAF to activate the MAPK pathway and enhance growth

Hatzivassiliou, G, Belvin, M, Stokoe, D, Ludlam, MJ, Alvarado, R, Morales, T, Jaiswal, BS, Seshagiri, S, Aliagas, I, Sideris, S, Malek, S, Koeppen, H, Gloor, SL, Vigers, G, Brandhuber, BJ, Liu, B, Yen, I, Friedman, LS, Anderson, DJ, Hoeflich, KP, Song, K

Nature 2010
20141835 Kinase-dead BRAF and oncogenic RAS cooperate to drive tumor progression through CRAF

Reis-Filho, JS, Heidorn, SJ, Springer, CJ, Pritchard, C, Nourry, A, Milagre, C, Whittaker, S, Dhomen, N, Marais, R, Niculescu-Duvas, I, Hussain, J

Cell 2010
16364920 Wild-type and mutant B-RAF activate C-RAF through distinct mechanisms involving heterodimerization

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

Mol. Cell 2005
25435214 Targeting RAS-ERK signalling in cancer: promises and challenges

Poulikakos, PI, Samatar, AA

Nat Rev Drug Discov 2014
15035987 Mechanism of activation of the RAF-ERK signaling pathway by oncogenic mutations of B-RAF

Niculescu-Duvaz, D, Lee, S, Marais, R, Marshall, CJ, Barford, D, Jones, CM, Good, VM, Springer, CJ, Wan, PT, Garnett, MJ, Roe, SM

Cell 2004
20179705 RAF inhibitors transactivate RAF dimers and ERK signalling in cells with wild-type BRAF

Shokat, KM, Zhang, C, Bollag, G, Rosen, N, Poulikakos, PI

Nature 2010
Participants
Participates
Catalyst Activity

protein serine/threonine/tyrosine kinase activity of RAS:GTP: inactive p-RAF:p-2S MAP2Ks:MAPKs:scaffold proteins [plasma membrane]

Normal reaction
Functional status

Gain of function of RAS:GTP: inactive p-RAF:p-2S MAP2Ks:MAPKs:scaffold proteins [plasma membrane]

Status
Disease
Name Identifier Synonyms
cancer DOID:162 malignant tumor, malignant neoplasm, primary cancer
Authored
Reviewed
Created
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