A conserved docking motif in MAP kinases common to substrates, activators and regulators

Mitogen-activated protein kinases (MAPKs) are specifically phosphorylated a nd activated by the MAPK kinases, phosphorylate various targets such as MAR K-activated protein kinases and transcription factors, and are inactivated by specific phosphatases. Recently, docking interactions via the non-cataly tic regions of MAPKs have been suggested to be important in regulating thes e reactions. Here we identify docking sites in MAPKs and in MAPK-interactin g enzymes. A docking domain in extracellular-signal-regulated kinase (ERK), a MAPK, serves as a common site for binding to the MAPK kinase MEK1, the M ARK-activated protein kinase MNK1 and the MAPK phosphatase MKP3. Two aspart ic acids in this domain are essential for docking, one of which is mutated in the sevenmaker mutant of Drosophila ERK/Rolled. A corresponding domain i n the MAPKs p38 and JNK/SAPK also serves as a common docking site for their MEKs, MAPK-activated protein kinases and MKPs. These docking interactions increase the efficiency of the enzymatic reactions. These findings reveal a hitherto unidentified docking motif in MAPKs that is used in common for re cognition of their activators, substrates and regulators.