Mitogen-activated protein kinases (MAPKs) are specifically phosphorylated
and activated by the MAPK kinases, phosphorylate various targets such as MAPK-activated
protein kinases and transcription factors, and are inactivated by specific
phosphatases. Recently, docking interactions via the non-catalytic regions
of MAPKs have been suggested to be important in regulating these reactions.
Here we identify docking sites in MAPKs and in MAPK-interacting 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 MAPK-activated protein
kinase MNK1 and the MAPK phosphatase MKP3. Two aspartic acids in this domain
are essential for docking, one of which is mutated in the sevenmaker
mutant of Drosophila ERK/Rolled. A corresponding domain in 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 recognition of their activators,
substrates and regulators.
