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).