Meta-Biol

• Pathways

Fusion mutants of BRAF and RAF1 are believed to form constitutive dimers and activate downstream signaling independent of RAS and external stimuli (Jones et al, 2008; Cin et al, 2011; Palanisamy et al, 2010; Ciampi et al, 2005; Stransky et al, 2014; Hutchinson et al, 2013; Zhang et al, 2013; Lee et al, 2012; Ricarte-Filho et al, 2013; reviewed in Lavoie and Therrien et al, 2015). The RAF portion of the fusion mutants may undergo phosphorylation of the N-region and activation loops similar to WT as shown in this reaction, although this has not been studied in detail. While WT RAF phosphorylation happens in the context of a complex with with RAS, this is unlikely to be the case for the fusion mutants, as many of these proteins lack the N-terminal RAS binding domain (reviewed in Lavoie and Therrien, 2015).