Meta-Biol

• Pathways

The atypical MAPKs MAPK6 (also known as ERK3) and MAPK4 (also known as ERK4) lack the conserved activation loop T-X-Y motif of the conventional MAPKs, and are thus not substrates for the dual-specificity MAPK kinases (reviewed in Coulombe and Meloche, 2007; Cargnello and Roux, 2011). The corresponding loop of MAPK6 and 4 instead contain a S-E-G motif that is phosphorylated at serine 189 and serine 186, respectively, by class I p21 activated kinases (PAKs) in a RAC- or CDC42-dependent manner (Deleris et al, 2008; Perander et al, 2008; Deleris et al, 2011; De La Mota-Peynado et al, 2011). Phosphorylation of the atypical MAPKs is not responsive to any identified extracellular stimulus, but rather occurs constitutively (Deleris et al, 2008).