Meta-Biol

• Pathways

MAPKs are inactivated by dephosphorylation of the activation loop T and Y residues by dual-specificity MAPK phosphatases (DUSPs) (reviewed in Roskoski, 2012b). Class 1 DUSPs, including DUSP 1, 2, 4 and 5 are nuclear and are generally activated by the same extracellular stimuli that promote MAPK signaling, establishing a negative feedback loop. DUSP5 is specific for MAPK3 and 1, while the other class 1 enzymes have broad specificity. Nuclear MAPKs may also be inactivated by nuclear forms of class III DUSPs, including DUSP8, 10 and 16, although the preferred substrate of these enzymes are the p38 and JNK MAP kinases (reviewed in Bermudez et al, 2010; Kondoh and Nishida, 2007).