Reactome | Dissociation of RAS:RAF complex

Dissociation of RAS:RAF complex

Stable Identifier

R-HSA-5672980

Type

Reaction [dissociation]

Species

Homo sapiens

Compartment

plasma membrane

ReviewStatus

5/5

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The mechanisms governing the dissociation or trafficking of activated MAPK signaling complexes at the plasma membrane are not fully worked out. Some active complexes may be endocytosed and targeted to other cellular locations, for example the Golgi complex (Lorentzen et al, 2010). Activated RAF monomers may dissociate and homo- or heterodimerize with additional inactive RAF monomers and in this way amplify the signal (reviewed in Matallanas et al, 2011; Cseh et al, 2014).
Ultimately, active RAF complexes are subject to PP5- and PP2A-mediated dephosphorylation, which promotes a return to the inactive state. Hydrolysis of RAS-bound GTP by the intrinsic GTPase activity, stimulated by association with RAS GAP proteins, ultimately promotes dissociation of RAS from RAF allowing a return to the quiescent state (reviewed in Wellbrock et al, 2004; Matallanas et al, 2011).

Literature References

PubMed ID	Title	Journal	Year
15520807	The RAF proteins take centre stage Wellbrock, C, Karasarides, M, Marais, R	Nat Rev Mol Cell Biol	2004
24937142	"RAF" neighborhood: protein-protein interaction in the Raf/Mek/Erk pathway Baccarini, M, Cseh, B, Doma, E	FEBS Lett.	2014
20858867	Regulation of Ras localization by acylation enables a mode of intracellular signal propagation Lorentzen, A, Bastiaens, PI, Kinkhabwala, A, Vartak, N, Rocks, O	Sci Signal	2010
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