Gene Symbol: MKP 7
Description: dual specificity phosphatase 16
Alias: MKP-7, MKP7, dual specificity protein phosphatase 16, MAP kinase phosphatase 7, MAPK phosphatase-7, mitogen-activated protein kinase phosphatase 7
Species: human
Products:     MKP 7

Top Publications

  1. Tanoue T, Yamamoto T, Maeda R, Nishida E. A Novel MAPK phosphatase MKP-7 acts preferentially on JNK/SAPK and p38 alpha and beta MAPKs. J Biol Chem. 2001;276:26629-39 pubmed
    ..MKP-5 and CL100/MKP-1 also bind to p38 alpha and -beta, but not gamma or delta. Finally, we propose a tentative classification of MKPs based on the sequence characteristics of their MAPK-docking site. ..
  2. Masuda K, Katagiri C, Nomura M, Sato M, Kakumoto K, Akagi T, et al. MKP-7, a JNK phosphatase, blocks ERK-dependent gene activation by anchoring phosphorylated ERK in the cytoplasm. Biochem Biophys Res Commun. 2010;393:201-6 pubmed publisher
    ..Reporter gene analysis indicated that MKP-7 blocks ERK-mediated transcription. Overall, our data indicate that MKP-7 down-regulates ERK-dependent gene expression by blocking nuclear accumulation of phospho-ERK. ..
  3. Hoornaert I, Marynen P, Goris J, Sciot R, Baens M. MAPK phosphatase DUSP16/MKP-7, a candidate tumor suppressor for chromosome region 12p12-13, reduces BCR-ABL-induced transformation. Oncogene. 2003;22:7728-36 pubmed
    ..Taken together, the functional data point to a context-dependent role for DUSP16 on cell transformation and apoptosis, reflecting the dual role of JNK, and therefore suggest that DUSP16 might be haploinsufficient for tumor suppression. ..
  4. Willoughby E, Collins M. Dynamic interaction between the dual specificity phosphatase MKP7 and the JNK3 scaffold protein beta-arrestin 2. J Biol Chem. 2005;280:25651-8 pubmed
    ..We previously demonstrated that the dual specificity phosphatases (DSPs) MKP7 and M3/6 bind the scaffold JNK-interacting protein-1 (JIP-1) and inactivate the bound subset of JNK (1)...
  5. Venkatesh K, Kumari A, Sen D. MicroRNA signature changes during induction of neural stem cells from human mesenchymal stem cells. Nanomedicine. 2019;: pubmed publisher
    ..The results could help in developing new strategies towards optimizing the in vitro differentiation of NSCs for potential use in future clinical applications. ..
  6. Kang Y, Jeong E, Seok H, Kim S, Hwang J, Choi M, et al. Cks1 regulates human hepatocellular carcinoma cell progression through osteopontin expression. Biochem Biophys Res Commun. 2019;508:275-281 pubmed publisher
    ..In conclusion, our data propose a novel function for Cks1 as a tumor promoter through the expression of the strongly oncogenic protein OPN in HCC. ..
  7. Ferguson B, Nam H, Morrison R. Dual-specificity phosphatases regulate mitogen-activated protein kinase signaling in adipocytes in response to inflammatory stress. Cell Signal. 2019;53:234-245 pubmed publisher
    ..This study highlights important roles for DUSPs as integral components of MAPK signaling and adipocyte inflammatory gene expression. ..
  8. Lu H, Tran L, Park Y, Chen I, Lan J, Xie Y, et al. Reciprocal Regulation of DUSP9 and DUSP16 Expression by HIF1 Controls ERK and p38 MAP Kinase Activity and Mediates Chemotherapy-Induced Breast Cancer Stem Cell Enrichment. Cancer Res. 2018;78:4191-4202 pubmed publisher
    ..i>Cancer Res; 78(15); 4191-202. ©2018 AACR. ..
  9. Zhang Y, Nallaparaju K, Liu X, Jiao H, Reynolds J, Wang Z, et al. MAPK phosphatase 7 regulates T cell differentiation via inhibiting ERK-mediated IL-2 expression. J Immunol. 2015;194:3088-95 pubmed publisher
    ..In this study, we show that MKP7, also known as dual-specificity phosphatase 16, was required for CD4(+) T cell responses in vivo...

More Information


  1. Park H, Park S, Nam S, Ryu S. Discovery of novel DUSP16 phosphatase inhibitors through virtual screening with homology modeled protein structure. J Biomol Screen. 2014;19:1383-90 pubmed publisher
    ..Structural features relevant to the stabilization of the newly identified inhibitors in the active site of DUSP16 are addressed in detail. ..
  2. Feurstein S, Rücker F, Bullinger L, Hofmann W, Manukjan G, Göhring G, et al. Haploinsufficiency of ETV6 and CDKN1B in patients with acute myeloid leukemia and complex karyotype. BMC Genomics. 2014;15:784 pubmed publisher
    ..Reduced gene dosage led to reduced gene expression levels, pointing to haploinsufficiency as the relevant mechanism of inactivation of ETV6 and CDKN1B in CK-AML. ..
  3. Li X, HE J, Li B, Gao M, Zeng Y, Lian J, et al. The PPAR? agonist rosiglitazone sensitizes the BH3 mimetic (-)-gossypol to induce apoptosis in cancer cells with high level of Bcl-2. Mol Carcinog. 2018;57:1213-1222 pubmed publisher
    ..This study may provide novel insights into the cancer therapeutics based on the combination of PPAR? agonists and BH3 mimetics. ..
  4. Maor Nof M, Romi E, Sar Shalom H, Ulisse V, Raanan C, Nof A, et al. Axonal Degeneration Is Regulated by a Transcriptional Program that Coordinates Expression of Pro- and Anti-degenerative Factors. Neuron. 2016;92:991-1006 pubmed publisher
    ..Overall, these results reveal that physiological axonal elimination is regulated by a transcriptional program that integrates regressive and progressive elements and identify Dusp16 as a new axonal preserving factor. ..
  5. Pan Q, Zhao F, Ye B. Eis, a novel family of arylalkylamine N-acetyltransferase (EC Sci Rep. 2018;8:2435 pubmed publisher
    ..These findings shed insights into the molecular mechanism of Eis, and reveal potential clinical implications for many gram-positive pathogens. ..
  6. Hwang J, Ham S, Yoo T, Lee W, Paek K, Kim J, et al. Upregulation of MKP-7 in response to rosiglitazone treatment ameliorates lipopolysaccharide-induced destabilization of SIRT1 by inactivating JNK. Pharmacol Res. 2016;114:47-55 pubmed publisher
    ..These results indicate that PPAR?-dependent upregulation of MKP-7 improves the stability of SIRT1 by inactivating JNK during inflammatory responses of LPS-activated macrophages. ..
  7. Guan Y, Wang S, Huang X, Xie Q, Xu Y, Shang D, et al. Nicotinamide Mononucleotide, an NAD+ Precursor, Rescues Age-Associated Susceptibility to AKI in a Sirtuin 1-Dependent Manner. J Am Soc Nephrol. 2017;28:2337-2352 pubmed publisher
    ..Furthermore, manipulation of SIRT1 activity by NMN seems to be a potential pharmaceutical intervention for AKI that could contribute to the precise treatment of aged patients with AKI. ..
  8. Ham S, Kang E, Lee H, Hwang J, Yoo T, Paek K, et al. PPAR? inhibits UVB-induced secretion of MMP-1 through MKP-7-mediated suppression of JNK signaling. J Invest Dermatol. 2013;133:2593-2600 pubmed publisher
    ..These results suggest that PPAR?-mediated inhibition of MMP-1 secretion prevents some effects of photoaging and maintains the integrity of skin by inhibiting the degradation of the collagenous extracellular matrix. ..
  9. Nizamutdinova I, Kim Y, Lee J, Chang K, Kim H. MKP-7, a negative regulator of JNK, regulates VCAM-1 expression through IRF-1. Cell Signal. 2012;24:866-72 pubmed publisher
    ..Thus, we suggest that MKP-7, a negative regulator of JNK, regulates VCAM-1 expression in activated endothelial cells through IRF-1 but not GATA6. ..
  10. Lee S, Syed N, Taylor J, Smith P, Griffin B, Baens M, et al. DUSP16 is an epigenetically regulated determinant of JNK signalling in Burkitt's lymphoma. Br J Cancer. 2010;103:265-74 pubmed publisher
    ..DUSP16 is a new epigenetically regulated determinant of JNK activation in BL. ..
  11. Willoughby E, Perkins G, Collins M, Whitmarsh A. The JNK-interacting protein-1 scaffold protein targets MAPK phosphatase-7 to dephosphorylate JNK. J Biol Chem. 2003;278:10731-6 pubmed
    ..Here we report that JIP-1 also binds the dual-specificity phosphatases MKP7 and M3/6 via a region independent of its JNK binding domain...
  12. Liu X, Zhang C, Lu C, Lin S, Wu J, Wang Z. A conserved motif in JNK/p38-specific MAPK phosphatases as a determinant for JNK1 recognition and inactivation. Nat Commun. 2016;7:10879 pubmed publisher
    ..Here we report the crystal structure of JNK1 bound to the catalytic domain of MKP7 at 2.4-Å resolution, providing high-resolution structural insight into the FXF-docking interaction...
  13. Masuda K, Shima H, Katagiri C, Kikuchi K. Activation of ERK induces phosphorylation of MAPK phosphatase-7, a JNK specific phosphatase, at Ser-446. J Biol Chem. 2003;278:32448-56 pubmed
    ..The COOH-terminal stretch of MKP-7 was shown to determine JNK preference for MKP-7 by masking MKP-7 activity toward p38 and is a domain bound by ERK. These data strongly suggested that Ser-446 of MKP-7 is phosphorylated by ERK. ..
  14. Patterson K, Brummer T, O Brien P, Daly R. Dual-specificity phosphatases: critical regulators with diverse cellular targets. Biochem J. 2009;418:475-89 pubmed
    ..The present review provides an overview of the DUSP family before focusing on atypical DUSPs, emerging as a group of proteins with vastly diverse substrate specificity and function. ..
  15. Zega K, Jovanovic V, Vitic Z, Niedzielska M, Knaapi L, Jukic M, et al. Dusp16 Deficiency Causes Congenital Obstructive Hydrocephalus and Brain Overgrowth by Expansion of the Neural Progenitor Pool. Front Mol Neurosci. 2017;10:372 pubmed publisher
    ..Moreover our results suggest that a lack of functional Dusp16 could play a central role in the molecular mechanisms linking brain overgrowth and hydrocephalus. ..
  16. Liu L, Zhu S, Jiang X, Ren J, Lin Y, Zhang N, et al. LncRNA Expression in CD4+ T Cells in Neurosyphilis Patients. Front Cell Infect Microbiol. 2017;7:461 pubmed publisher
    ..pallidum infection in neurosyphilis patients. LncRNAs are involved in key biological processes that comprise the CD4+ T cell response to the T. pallidum infection...
  17. Bose A, Janes K. A high-throughput assay for phosphoprotein-specific phosphatase activity in cellular extracts. Mol Cell Proteomics. 2013;12:797-806 pubmed publisher
    ..Our assay platform should be beneficial for phosphoproteomic surveys and computational-systems models of signaling, where phosphatases are known to be important but their activities are rarely measured. ..
  18. Katagiri C, Masuda K, Urano T, Yamashita K, Araki Y, Kikuchi K, et al. Phosphorylation of Ser-446 determines stability of MKP-7. J Biol Chem. 2005;280:14716-22 pubmed
    ..These results indicate that activation of the ERK pathway strongly blocks JNK activation through stabilization of MKP-7 mediated by phosphorylation. ..
  19. Masuda K, Shima H, Watanabe M, Kikuchi K. MKP-7, a novel mitogen-activated protein kinase phosphatase, functions as a shuttle protein. J Biol Chem. 2001;276:39002-11 pubmed
    ..Co-immunoprecipitation experiments and histological analysis suggested that MKP-7 determines the localization of MAPKs in the cytoplasm. ..
  20. Li J, Zhou J, Xu Z, Huang H, Chen M, Ji J. MicroRNA-27a-3p inhibits cell viability and migration through down-regulating DUSP16 in hepatocellular carcinoma. J Cell Biochem. 2017;: pubmed publisher
    ..This article is protected by copyright. All rights reserved...
  21. Zhang H, Zheng H, Mu W, He Z, Yang B, Ji Y, et al. DUSP16 ablation arrests the cell cycle and induces cellular senescence. FEBS J. 2015;282:4580-94 pubmed publisher
    ..Taken together, our findings indicate that DUSP16 plays a role in tumorigenesis by protecting cancer cells from senescence. ..
  22. Kumar G, Zettl H, Page R, Peti W. Structural basis for the regulation of the mitogen-activated protein (MAP) kinase p38? by the dual specificity phosphatase 16 MAP kinase binding domain in solution. J Biol Chem. 2013;288:28347-56 pubmed publisher
    ..Together, these structural and energetic differences in p38? engagement highlight the fine-tuning necessary to achieve MAPK specificity and regulation among multiple regulatory proteins. ..
  23. Al Shehhi H, Konn Z, Schwab C, Erhorn A, Barber K, Wright S, et al. Abnormalities of the der(12)t(12;21) in ETV6-RUNX1 acute lymphoblastic leukemia. Genes Chromosomes Cancer. 2013;52:202-13 pubmed publisher
    ..In conclusion, this study has defined novel abnormalities in ETV6-RUNX1 BCP-ALL, which implicate new genes involved in leukemogenesis. ..
  24. Finch A, Caunt C, Perrett R, Tsaneva Atanasova K, McArdle C. Dual specificity phosphatases 10 and 16 are positive regulators of EGF-stimulated ERK activity: indirect regulation of ERK signals by JNK/p38 selective MAPK phosphatases. Cell Signal. 2012;24:1002-11 pubmed publisher
  25. Pi X, Wu Y, Ferguson J, Portbury A, Patterson C. SDF-1alpha stimulates JNK3 activity via eNOS-dependent nitrosylation of MKP7 to enhance endothelial migration. Proc Natl Acad Sci U S A. 2009;106:5675-80 pubmed publisher
    ..SDF-1alpha-induced signaling cascade that involves endothelial nitric oxide synthase (eNOS), JNK3, and MAPK phosphatase 7 (MKP7)...
  26. Jeong D, Wei C, Ku B, Jeon T, Chien P, Kim J, et al. The family-wide structure and function of human dual-specificity protein phosphatases. Acta Crystallogr D Biol Crystallogr. 2014;70:421-35 pubmed publisher
    ..The family-wide structures of DUSPs form a basis for the understanding of phosphorylation-mediated signal transduction and the development of therapeutics. ..