| First Author | Masuda K | Year | 2001 |
| Journal | J Biol Chem | Volume | 276 |
| Issue | 42 | Pages | 39002-11 |
| PubMed ID | 11489891 | Mgi Jnum | J:72184 |
| Mgi Id | MGI:2151972 | Doi | 10.1074/jbc.M104600200 |
| Citation | Masuda K, et al. (2001) Mkp-7, a novel mitogen-activated protein kinase phosphatase, functions as a shuttle protein. J Biol Chem 276(42):39002-11 |
| abstractText | 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. |
