The BioGRID | PUBLICATION VIEW

	J. Biol. Chem. Mar (2003); 278(12):10731-6
The JNK-interacting protein-1 scaffold protein targets MAPK phosphatase-7 to dephosphorylate JNK.
Willoughby EA, Perkins GR, Collins MK, Whitmarsh AJ
Department of Immunology and Molecular Pathology, University College London and Royal Free Medical School, Windeyer Institute, United Kingdom.
Abstract: 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.
[PUBMED: 12524447]