Dissociation of RAS:RAF complex

Stable Identifier
Reaction [dissociation]
Homo sapiens
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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
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