Phosphatase Subfamily DSP14
Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily DSP14
Eumetazoan-specific subfamily acting on MAPK cascade.
Evolution
DSP14 emerged in eumetazoa and duplicated in vertebrates, giving rise to four human members: DUSP14 (MKP6), DUSP18, DUSP21 and DUSP28.
Domain
DSP14 subfamily has a single phosphatase domain.
Function
DUSP14 (MKP6) dephosphorylates TGF-beta-activated kinase 1 (TAK1), a member of MAPKKK, at Thr-187 within its kinase activation loop. Thus, DUSP14 negatively regulates TNF- or IL-1-induced NF-kappaB activation [1]. DUSP14 is widely expressed in different tissues with highest expression in skin tissues (see GTEx).
DUSP18 interacts with and dephosphorylates SAPK/JNK in vitro and in vivo. It does not dephosphorylate p38 or ERK1 [2]. USP18 was widely expressed in different tissues as evidenced by RT-PCR [3]. RNA-seq from GTEx shows a high expression in testis and pituitary, and a low expression in skeleton.
DUSP21 plays an important role in sustaining human hepatocellular carcinoma cell proliferation [4].
DUSP28 (VHP) is widely expressed in different tissues according to RNA-seq data from GTEx, but its function is unknown.
References
- Zheng H, Li Q, Chen R, Zhang J, Ran Y, He X, Li S, and Shu HB. The dual-specificity phosphatase DUSP14 negatively regulates tumor necrosis factor- and interleukin-1-induced nuclear factor-κB activation by dephosphorylating the protein kinase TAK1. J Biol Chem. 2013 Jan 11;288(2):819-25. DOI:10.1074/jbc.M112.412643 |
- Wu Q, Huang S, Sun Y, Gu S, Lu F, Dai J, Yin G, Sun L, Zheng D, Dou C, Feng C, Ji C, Xie Y, and Mao Y. Dual specificity phosphotase 18, interacting with SAPK, dephosphorylates SAPK and inhibits SAPK/JNK signal pathway in vivo. Front Biosci. 2006 Sep 1;11:2714-24. DOI:10.2741/2001 |
- Wu Q, Gu S, Dai J, Dai J, Wang L, Li Y, Zeng L, Xu J, Ye X, Zhao W, Ji C, Xie Y, and Mao Y. Molecular cloning and characterization of a novel dual-specificity phosphatase18 gene from human fetal brain. Biochim Biophys Acta. 2003 Feb 20;1625(3):296-304. DOI:10.1016/s0167-4781(02)00629-2 |
- Deng Q, Li KY, Chen H, Dai JH, Zhai YY, Wang Q, Li N, Wang YP, and Han ZG. RNA interference against cancer/testis genes identifies dual specificity phosphatase 21 as a potential therapeutic target in human hepatocellular carcinoma. Hepatology. 2014 Feb;59(2):518-30. DOI:10.1002/hep.26665 |
