Phosphatase Subfamily DSP8

Phosphatase Classification: Superfamily CC1: Family DSP: Subfamily DSP8

Evolution

DSP8 is found in metazoan, typically single-copy, but expanded to two genes, DUSP8 and DUSP16 in human.

Domain Structure

Human DUSP16 possesses a long C-terminal stretch containing both a nuclear export signal and a nuclear localization signal, in addition to the rhodanese domain and the dual specificity phosphatase catalytic domain, both of which are conserved among MKP family members.

Functions

DUSP16 (MKP7)

DUSP16 is predominantly localized in the cytoplasm when expressed in cultured cells, whereas DUSP8 (hVH5) is both in the nucleus and the cytoplasm. Its localization became exclusively nuclear following leptomycin B treatment or introduction of a mutation in the nuclear export signal. DUSP16 binds to and inactivates p38 MAPK and JNK/SAPK, but not ERK. In particular, DUSP16 binds to and inactivates p38 alpha and -beta isoforms, but not gamma or delta. A mutant form DUSP16 functioned as a dominant negative particularly against the dephosphorylation of JNK, suggesting that DUSP16 works as a JNK-specific phosphatase in vivo [1, 2].

References

1. Masuda K, Shima H, Watanabe M, and Kikuchi K. MKP-7, a novel mitogen-activated protein kinase phosphatase, functions as a shuttle protein. J Biol Chem. 2001 Oct 19;276(42):39002-11. DOI:10.1074/jbc.M104600200 |
2. Tanoue T, Yamamoto T, Maeda R, and Nishida E. A Novel MAPK phosphatase MKP-7 acts preferentially on JNK/SAPK and p38 alpha and beta MAPKs. J Biol Chem. 2001 Jul 13;276(28):26629-39. DOI:10.1074/jbc.M101981200 |