title: The JNK-interacting protein-1 scaffold protein targets MAPK phosphatase-7 to dephosphorylate JNK.
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.
authors.affiliation: Department of Immunology and Molecular Pathology, University College London and Royal Free Medical School, Windeyer Institute, United Kingdom.
authors.forename: Emma A
authors.initials: EA
authors.lastname: Willoughby
authors.forename: Gordon R
authors.initials: GR
authors.lastname: Perkins
authors.forename: Mary K
authors.initials: MK
authors.lastname: Collins
authors.forename: Alan J
authors.initials: AJ
authors.lastname: Whitmarsh
mesh_terms: D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D019556:COS Cells; D002352:Carrier Proteins / Q000378:metabolism* / Q000502:physiology; D054637:Dual-Specificity Phosphatases; D048031:JNK Mitogen-Activated Protein Kinases; D051379:Mice; D054639:Mitogen-Activated Protein Kinase Phosphatases; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism*; D010766:Phosphorylation; D017027:Protein Tyrosine Phosphatases / Q000378:metabolism*; D016755:Proto-Oncogene Proteins c-jun / Q000378:metabolism
chemical_list: D048868:Adaptor Proteins, Signal Transducing; D002352:Carrier Proteins; C490666:MAPK8IP1 protein, human; C408376:MAPK8IP2 protein, human; C490665:Mapk8ip protein, mouse; C486564:Mapk8ip2 protein, mouse; D016755:Proto-Oncogene Proteins c-jun; D048031:JNK Mitogen-Activated Protein Kinases; D020928:Mitogen-Activated Protein Kinases; D054639:Mitogen-Activated Protein Kinase Phosphatases; C439065:DUSP16 protein, human; D054637:Dual-Specificity Phosphatases; D017027:Protein Tyrosine Phosphatases