Difference between revisions of "Phosphatase Subfamily DSP10"

Revision as of 19:28, 12 September 2018

Phosphatase Classification: Fold CC1: Superfamily CC1: Family DSP: Subfamily DSP10 (MKP5)

Human DSP10 selectively dephosphorylates p38 and JNK. It is conserved across holozoa but lost in nematodes.

Evolution

The DSP10 (MKP5) subfamily is found in most holozoa. DSP10 is usually one copy per genome, e.g. DUSP10 (MKP5) in human. DSP10 is lost from nematodes, and dipteran insects have lost the rhodanese domain.

Domain

The DSP10 (MKP5) has two domains: rhodanese domain and phosphatase domain. The rhodanese domain can bind to kinases [1]. Drosophila has lost the whole rhodanese domain.

Function

Human DUSP10 is a phosphatase specific for p38 and SAPK/JNK. It binds to p38 and SAPK/JNK, but not to MAPK/ERK, and inactivates p38 and SAPK/JNK, but not MAPK/ERK. p38 is a preferred substrate. It is present evenly in both the cytoplasm and the nucleus. DUSP10 is widely expressed in various tissues and organs, and its expression in cultured cells is elevated by stress stimuli [2, 3, 4].

On the other hand, it has been reported that human DUSP10 interacts with ERK, retains it in the cytoplasm, suppresses its activation and downregulates ERK-dependent transcription [5].

Human DUSP10 is frequently upregulated in colorectal cancer (CRC). Certain mutations in DUSP10 correlate with the incidence of CRC. DUSP10/MKP5 also negatively regulates intestinal epithelial cell growth [6].

Human DUSP10 (MKP5) is implicated in immune system. It functions in the type I interferon system responding to viral infection. It interacts with, dephosphorylates and inactivates Interferon regulatory factor 3 (IRF3), an interferon regulatory factor which plays an important role in the type I interferon system. Increased type I interferon responses were observed in DUSP10/MKP5-deficient cells and animals upon various RNA virus infection, including H1N1 influenza virus, vesicular stomatitis virus and sendai virus [7]. DUSP10/MKP5 also regulates adipose tissue inflammation and insulin resistance [8].

Technical notes

Rhodanese domain lost in diptera

We observed the lost of rhodanese domain in Drosophila melanogaster. We then asked when the lose happened, it was lost in D. melanogaster only, or in all arthropods, or somewhere in between. We obtained all the DSP10s from our internal orthology database, searched the Pfam domains using Pfam web server (E-value cutoff 1.0), and eyeballed the presence and absence of rhodanese domain in 31 arthropods. We found the rhodanese domain was lost in diptera and is generally present in other arthropods.

References

1. Tao X and Tong L. Crystal structure of the MAP kinase binding domain and the catalytic domain of human MKP5. Protein Sci. 2007 May;16(5):880-6. DOI:10.1110/ps.062712807 | PubMed ID:17400920 | HubMed [Tao07]
2. Tanoue T, Moriguchi T, and Nishida E. Molecular cloning and characterization of a novel dual specificity phosphatase, MKP-5. J Biol Chem. 1999 Jul 9;274(28):19949-56. DOI:10.1074/jbc.274.28.19949 | PubMed ID:10391943 | HubMed [Tanoue99]
3. Theodosiou A, Smith A, Gillieron C, Arkinstall S, and Ashworth A. MKP5, a new member of the MAP kinase phosphatase family, which selectively dephosphorylates stress-activated kinases. Oncogene. 1999 Nov 25;18(50):6981-8. DOI:10.1038/sj.onc.1203185 | PubMed ID:10597297 | HubMed [Theodosiou99]
4. Jeong DG, Yoon TS, Kim JH, Shim MY, Jung SK, Son JH, Ryu SE, and Kim SJ. Crystal structure of the catalytic domain of human MAP kinase phosphatase 5: structural insight into constitutively active phosphatase. J Mol Biol. 2006 Jul 28;360(5):946-55. DOI:10.1016/j.jmb.2006.05.059 | PubMed ID:16806267 | HubMed [Jeong06]
5. Nomura M, Shiiba K, Katagiri C, Kasugai I, Masuda K, Sato I, Sato M, Kakugawa Y, Nomura E, Hayashi K, Nakamura Y, Nagata T, Otsuka T, Katakura R, Yamashita Y, Sato M, Tanuma N, and Shima H. Novel function of MKP-5/DUSP10, a phosphatase of stress-activated kinases, on ERK-dependent gene expression, and upregulation of its gene expression in colon carcinomas. Oncol Rep. 2012 Sep;28(3):931-6. DOI:10.3892/or.2012.1862 | PubMed ID:22711061 | HubMed [Nomura12]
6. Png CW, Weerasooriya M, Guo J, James SJ, Poh HM, Osato M, Flavell RA, Dong C, Yang H, and Zhang Y. DUSP10 regulates intestinal epithelial cell growth and colorectal tumorigenesis. Oncogene. 2016 Jan 14;35(2):206-17. DOI:10.1038/onc.2015.74 | PubMed ID:25772234 | HubMed [Png15]
7. James SJ, Jiao H, Teh HY, Takahashi H, Png CW, Phoon MC, Suzuki Y, Sawasaki T, Xiao H, Chow VTK, Yamamoto N, Reynolds JM, Flavell RA, Dong C, and Zhang Y. MAPK Phosphatase 5 Expression Induced by Influenza and Other RNA Virus Infection Negatively Regulates IRF3 Activation and Type I Interferon Response. Cell Rep. 2015 Mar 17;10(10):1722-1734. DOI:10.1016/j.celrep.2015.02.030 | PubMed ID:25772359 | HubMed [James15]
8. Zhang Y, Nguyen T, Tang P, Kennedy NJ, Jiao H, Zhang M, Reynolds JM, Jaeschke A, Martin-Orozco N, Chung Y, He WM, Wang C, Jia W, Ge B, Davis RJ, Flavell RA, and Dong C. Regulation of Adipose Tissue Inflammation and Insulin Resistance by MAPK Phosphatase 5. J Biol Chem. 2015 Jun 12;290(24):14875-83. DOI:10.1074/jbc.M115.660969 | PubMed ID:25922079 | HubMed [Zhang15]