ERK1/2-mediated feedback inhibition down-regulates signalling by ERK1/2-catalysed phosphorylation of SOS, RAF and MEK1/2 to prevent hyperstimulation of ERK signalling. SOS phosphorylation reduces RAS activation. Phosphorylation of RAF prevents dimerisation and therefore kinase signalling. Finally, feedback phosphorylation of MEK1 prevents its activation. Class I BRAF mutants signal as monomers regardless of RAS activity, and are unaffected by ERK1/2 feedback inhibition through SOS and the disruption of RAF dimer formation. Class II BRAF mutants signal constitutively as dimers independently of RAS activity so they are susceptible to feedback disruption of RAF dimers and MEK1/2 activation but are not susceptible to SOS phosphorylation. Finally class III RAF mutants are still reliant on RAS for dimerisation and activity, and therefore are susceptible to all direct feedback inhibition mechanisms of ERK1/2.