Reactome | RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs

RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs

Stable Identifier

R-HSA-6802914

Type

Reaction [binding]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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RAS:GTP:moderate kinase activity p-RAF complexes bind MAP2Ks and MAPKs

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RAF dimerization and phosphorylation downstream of moderately activating BRAF mutations is associated with increased MAP2K and MAPK phosphorylation (Wan et al, 2004; Freeman et al, 2013; Roring et al, 2012; reviewed in Holderfield et al, 2014; Lavoie and Therrien, 2015). Although the interactions between oncogenic RAS or RAFs and downstream effectors hasn'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
25907612	Regulation of RAF protein kinases in ERK signalling Lavoie, H, Therrien, M	Nat. Rev. Mol. Cell Biol.	2015
22510884	Distinct requirement for an intact dimer interface in wild-type, V600E and kinase-dead B-Raf signalling Fiala, GJ, Herr, R, Röring, M, Heilmann, K, Schamel, WW, Saunders, DN, Halbach, S, Capper, D, Brummer, T, Braun, S, von Deimling, A, Eisenhardt, AE	EMBO J.	2012
24957944	Targeting RAF kinases for cancer therapy: BRAF-mutated melanoma and beyond McCormick, F, Deuker, MM, McMahon, M, Holderfield, M	Nat. Rev. Cancer	2014
23352452	Effects of Raf dimerization and its inhibition on normal and disease-associated Raf signaling Freeman, AK, Ritt, DA, Morrison, DK	Mol. Cell	2013
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
21779496	Raf family kinases: old dogs have learned new tricks Romano, D, Matallanas, D, Rauch, J, Zebisch, A, Birtwistle, M, Kolch, W, von Kriegsheim, A	Genes Cancer	2011