Format

Send to

Choose Destination
J Biol Chem. 2001 Oct 19;276(42):39002-11. Epub 2001 Aug 6.

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

Author information

1
Division of Biochemical Oncology and Immunology, Institute for Genetic Medicine, Hokkaido University, Kita-15, Nishi-7, Kita-ku, Sapporo 060-0815, Japan.

Abstract

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.

PMID:
11489891
DOI:
10.1074/jbc.M104600200
[Indexed for MEDLINE]
Free full text

Publication type, MeSH terms, Substances, Secondary source ID

Publication type

MeSH terms

Substances

Secondary source ID

Supplemental Content

Full text links

Icon for HighWire
Loading ...
Support Center