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The JNK-interacting protein-1 scaffold protein targets MAPK phosphatase-7 to dephosphorylate JNK.

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 ID: 12524447

Authors

  • Willoughby EA
  • Perkins GR
  • Collins MK
  • Whitmarsh AJ

Journal

The Journal of biological chemistry

Publication Data

March 21, 2003

Associated Grants

None

Mesh Terms

  • Adaptor Proteins, Signal Transducing
  • Animals
  • COS Cells
  • Carrier Proteins
  • Dual-Specificity Phosphatases
  • JNK Mitogen-Activated Protein Kinases
  • Mice
  • Mitogen-Activated Protein Kinase Phosphatases
  • Mitogen-Activated Protein Kinases
  • Phosphorylation
  • Protein Tyrosine Phosphatases
  • Proto-Oncogene Proteins c-jun