Meta-Biol

• Pathways

Although they occur at much lower frequently than mutations in upstream components of the RAS signaling pathway, activating mutations in MAP2K proteins, encoding MEK1 and MEK2, have been identified in a number of cancers and germline disorders (Marks et al, 2008; Murugan et al, 2009). These mutations cluster in the N-terminal autoinhibitory domain or in the catalytic domain and lead to constitutively active forms of the proteins that phosphorylate MAPK1 and MAPK2 (ERK2 and ERK1) independent of upstream signaling (Nikolaev et al, 2011; Rodriguez-Viciana and Rauen, 2008; Borttoff et al, 1995; Marks et al, 2008; Estep et al, 2007; Van Allen et al, 2014; Chen et al, 2014; Wagle et al, 2011; Waterfall et al, 2014; Rauen et al, 2010; reviewed in Samatar and Poulikakos, 2014; Rauen, 2013; Bezniakow et al, 2014).