MAP kinases are inactivated by dual-specificity protein phosphatases (DUSP) that differ in their substrate specificity, tissue distribution, inducibility by extracellular stimuli and cellular localization. DUSPs, also known as MAPK phosphatases (MKP), specifically dephosphorylate both threonine and tyrosine residues in MAPK P-loops and have been shown to play important roles in regulating the function of the MAPK family (1,2). At least 13 members of the family (DUSP1-10, DUSp14, DUSP16, and DUSP22) display unique substrate specificities for various MAP kinases (3). MAPK phosphatases typically contain an amino-terminal rhodanese-fold responsible for DUSP docking to MAPK family members and a carboxy-terminal catalytic domain (4). These phosphatases can play important roles in development, immune system function, stress responses and metabolic homeostasis (5), and also in the development of cancer and the response of cancer cells to chemotherapy (6).DUSP6 specifically dephosphorylates ERK MAP kinase (7).
