Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions

MAP kinases (MAPKs) form a complex with MAPK kinases (MAPKKs), MAPK-specifi c phosphatases (MKPs) and various targets including MAPKAPKs, These docking interactions contribute to regulation of the specificity and efficiency of the enzymatic reactions. We have previously identified a docking site on M APKs, termed the CD (common docking) domain, which is utilized commonly for docking interactions with MAPKKs, MKPs and MAPKAPKs, However, the CD domai n alone does not determine the docking specificity. Here we have identified a novel site on p38 and ERK2 MAPKs that regulates the docking specificity towards MAPKAPKs, Remarkably, exchange of two amino acids in this site of E RK2 for corresponding residues of p38 converted the docking specificity for MAPKAPK-3/3pk, which is a dominant target of p38, from the ERK2 type to th e p38 type, and vice versa, Furthermore, our detailed analyses with a numbe r of MAPKAPKs and MKPs suggest that a groove in the steric structure of MAP Ks, which comprises the CD domain and the site identified here, serves as a common docking region for various MAPK-interacting molecules.