MKP-7, a novel mitogen-activated protein kinase phosphatase, functions as a shuttle protein
In: The Journal of biological chemistry, Jg. 276 (2001-08-08), Heft 42
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Zugriff:
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.
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MKP-7, a novel mitogen-activated protein kinase phosphatase, functions as a shuttle protein
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Autor/in / Beteiligte Person: | Kikuchi, Kunimi ; Shima, Hiroshi ; Watanabe, Masahiko ; Masuda, Kouhei |
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Zeitschrift: | The Journal of biological chemistry, Jg. 276 (2001-08-08), Heft 42 |
Veröffentlichung: | 2001 |
Medientyp: | unknown |
ISSN: | 0021-9258 (print) |
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