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MKP-7, a novel mitogen-activated protein kinase phosphatase, functions as a shuttle protein.

Mitogen-activated protein kinase (MAPK) phosphatases (MKPs) negatively regulate MAPK activity. In the present study, we have identified a novel MKP, designated MKP-7, and mapped it to human chromosome 12p12. MKP-7 possesses a long C-terminal stretch containing both a nuclear export signal and a nuclear localization signal, in addition to the rhodanese-like domain and the dual specificity phosphatase catalytic domain, both of which are conserved among MKP family members. When expressed in mammalian cells MKP-7 protein was localized exclusively in the cytoplasm, but this localization became exclusively nuclear following leptomycin B treatment or introduction of a mutation in the nuclear export signal. These findings indicate that MKP-7 is the first identified leptomycin B-sensitive shuttle MKP. Forced expression of MKP-7 suppressed activation of MAPKs in COS-7 cells in the order of selectivity, JNK p38 > ERK. Furthermore, a mutant form MKP-7 functioned as a dominant negative particularly against the dephosphorylation of JNK, suggesting that MKP-7 works as a JNK-specific phosphatase in vivo. Co-immunoprecipitation experiments and histological analysis suggested that MKP-7 determines the localization of MAPKs in the cytoplasm.

Pubmed ID: 11489891

Authors

  • Masuda K
  • Shima H
  • Watanabe M
  • Kikuchi K

Journal

The Journal of biological chemistry

Publication Data

October 19, 2001

Associated Grants

None

Mesh Terms

  • Active Transport, Cell Nucleus
  • Amino Acid Motifs
  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Blotting, Northern
  • COS Cells
  • Carrier Proteins
  • Catalytic Domain
  • Cell Nucleus
  • Chromosome Mapping
  • Chromosomes, Human, Pair 12
  • Cytoplasm
  • DNA, Complementary
  • Databases as Topic
  • Dual-Specificity Phosphatases
  • Exons
  • Expressed Sequence Tags
  • Fatty Acids, Unsaturated
  • Genes, Dominant
  • HeLa Cells
  • Humans
  • JNK Mitogen-Activated Protein Kinases
  • MAP Kinase Kinase 4
  • MAP Kinase Signaling System
  • Mice
  • Mitogen-Activated Protein Kinase Kinases
  • Mitogen-Activated Protein Kinase Phosphatases
  • Mitogen-Activated Protein Kinases
  • Models, Genetic
  • Molecular Sequence Data
  • Mutation
  • Phosphorylation
  • Plasmids
  • Precipitin Tests
  • Protein Binding
  • Protein Structure, Tertiary
  • Protein Tyrosine Phosphatases
  • Sequence Homology, Amino Acid
  • Substrate Specificity
  • Tissue Distribution
  • Transfection
  • p38 Mitogen-Activated Protein Kinases