The c-Jun N-terminal kinase (JNK) group of mitogen-activated protein kinases 
(MAPKs) are activated by pleiotropic signals including environmental stresses, 
growth factors, and hormones. A subset of JNK can bind to distinct scaffold 
proteins that also bind upstream kinases of the JNK pathway, allowing sequential 
kinase activation within a signaling module. The JNK-interacting protein-1 
(JIP-1) scaffold protein specifically binds JNK, MAP kinase kinase 7, and 
members of the MLK family and is essential for stress-mediated JNK activation in 
neurones. Here we report that JIP-1 also binds the dual-specificity phosphatases 
MKP7 and M3/6 via a region independent of its JNK binding domain. The C-terminal 
region of MKP7, homologous to that of M3/6 but not other DSPs, is required for 
interaction with JIP-1. When MKP7 is bound to JIP-1 it reduces JNK activation 
leading to reduced phosphorylation of the JNK target c-Jun. These results 
indicate that the JIP-1 scaffold protein modulates JNK signaling via association 
with both protein kinases and protein phosphatases that target JNK.