JNK scaffold proteins bind JNK and upstream kinases to activate subsets of JNK 
and localize activated JNK to specific subcellular sites. We previously 
demonstrated that the dual specificity phosphatases (DSPs) MKP7 and M3/6 bind 
the scaffold JNK-interacting protein-1 (JIP-1) and inactivate the bound subset 
of JNK (1). The G protein-coupled receptor (GPCR) adaptor beta-arrestin 2 is 
also a JNK3 scaffold. It binds the upstream kinases ASK1 and MKK4 and couples 
stimulation of the angiotensin II receptor AT1aR to activation of a cytoplasmic 
pool of JNK3. Here we report that MKP7 also binds beta-arrestin 2 via amino 
acids 394-443 of MKP7, the same region that interacts with JIP-1. This region of 
MKP7 interacts with beta-arrestin 2 at a central region near the JNK binding 
domain. MKP7 dephosphorylates JNK3 bound to beta-arrestin 2, either following 
activation by ASK1 overexpression or following AT1aR stimulation. Initial AT1aR 
stimulation causes a rapid (within 5 min) dissociation of MKP7 from 
beta-arrestin 2. MKP7 then reassociates with beta-arrestin 2 on endocytic 
vesicles 30-60 min after initial receptor stimulation. This dynamic interaction 
between phosphatase and scaffold permits signal transduction through a module 
that binds both positive and negative regulators.