DUSP6

Summary

Gene Symbol: DUSP6
Description: dual specificity phosphatase 6
Alias: HH19, MKP3, PYST1, dual specificity protein phosphatase 6, MAP kinase phosphatase 3, dual specificity protein phosphatase PYST1, mitogen-activated protein kinase phosphatase 3, serine/threonine specific protein phosphatase
Species: human
Products:     DUSP6

Top Publications

  1. Camps M, Nichols A, Gillieron C, Antonsson B, Muda M, Chabert C, et al. Catalytic activation of the phosphatase MKP-3 by ERK2 mitogen-activated protein kinase. Science. 1998;280:1262-5 pubmed
    ..Catalytic activation of MAP kinase phosphatases through substrate binding may regulate MAP kinase activation by a large number of receptor systems. ..
  2. Zhang Z, Kobayashi S, Borczuk A, Leidner R, LaFramboise T, Levine A, et al. Dual specificity phosphatase 6 (DUSP6) is an ETS-regulated negative feedback mediator of oncogenic ERK signaling in lung cancer cells. Carcinogenesis. 2010;31:577-86 pubmed publisher
    ..In the current study, we focus on the assessment of DUSP6, a cytoplasmic DUSP with high specificity for extracellular signal-regulated kinase (ERK)...
  3. Rodriguez J, Crespo P. Working without kinase activity: phosphotransfer-independent functions of extracellular signal-regulated kinases. Sci Signal. 2011;4:re3 pubmed publisher
  4. 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. ..
  5. Rossig L, Hermann C, Haendeler J, Assmus B, Zeiher A, Dimmeler S. Angiotensin II-induced upregulation of MAP kinase phosphatase-3 mRNA levels mediates endothelial cell apoptosis. Basic Res Cardiol. 2002;97:1-8 pubmed
    ..These results indicate that Ang II-induced apoptosis signaling in human EC is mediated via MKP-3-dependent dephosphorylation of ERK1/2, which in turn leads to the degradation of Bcl-2. ..
  6. Xu S, Furukawa T, Kanai N, Sunamura M, Horii A. Abrogation of DUSP6 by hypermethylation in human pancreatic cancer. J Hum Genet. 2005;50:159-67 pubmed
    Our previous study indicated that DUSP6/MKP-3/PYST1 could act as a tumor suppressor in human pancreatic cancer. DUSP6 was frequently underexpressed in primary pancreatic cancer tissues by an unknown mechanism...
  7. Amit I, Citri A, Shay T, Lu Y, Katz M, Zhang F, et al. A module of negative feedback regulators defines growth factor signaling. Nat Genet. 2007;39:503-12 pubmed
    ..More generally, our study proposes a mechanistic description of the cellular response to growth factors by defining architectural motifs that underlie the function of signaling networks. ..
  8. Okudela K, Yazawa T, Woo T, Sakaeda M, Ishii J, Mitsui H, et al. Down-regulation of DUSP6 expression in lung cancer: its mechanism and potential role in carcinogenesis. Am J Pathol. 2009;175:867-81 pubmed publisher
    ..After a comprehensive search for genes whose expression levels were modulated by KRAS/V12, we focused on DUSP6, a pivotal negative feedback regulator of the RAS-ERK pathway...
  9. Furukawa T, Fujisaki R, Yoshida Y, Kanai N, Sunamura M, Abe T, et al. Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas. Mod Pathol. 2005;18:1034-42 pubmed
    b>DUSP6/MKP-3 is identified as a candidate tumor suppressor gene for pancreatic cancer...

More Information

Publications101 found, 100 shown here

  1. Jurek A, Amagasaki K, Gembarska A, Heldin C, Lennartsson J. Negative and positive regulation of MAPK phosphatase 3 controls platelet-derived growth factor-induced Erk activation. J Biol Chem. 2009;284:4626-34 pubmed publisher
    ..In the present study, we provide evidence that platelet-derived growth factor BB (PDGF-BB) regulates MKP3 (DUSP6), which is considered to be a phosphatase highly selective for Erk...
  2. Nunes Xavier C, Tárrega C, Cejudo Marín R, Frijhoff J, Sandin A, Ostman A, et al. Differential up-regulation of MAP kinase phosphatases MKP3/DUSP6 and DUSP5 by Ets2 and c-Jun converge in the control of the growth arrest versus proliferation response of MCF-7 breast cancer cells to phorbol ester. J Biol Chem. 2010;285:26417-30 pubmed publisher
    ..MKP3/DUSP6 and DUSP5 MAP kinase phosphatases, two negative regulators of ERK1/2, were specifically up-regulated in MCF-7 and ..
  3. Messina S, Frati L, Leonetti C, Zuchegna C, Di Zazzo E, Calogero A, et al. Dual-specificity phosphatase DUSP6 has tumor-promoting properties in human glioblastomas. Oncogene. 2011;30:3813-20 pubmed publisher
    Dual-specificity phosphatase 6 (DUSP6, mitogen-activated protein kinase (MAPK) phosphatase 3 or PYST1) dephosphorylates phosphotyrosine and phosphothreonine residues on extracellular signal-regulated kinase (ERK1/2; MAPK1/2) to ..
  4. Cejudo Marín R, Tárrega C, Nunes Xavier C, Pulido R. Caspase-3 cleavage of DUSP6/MKP3 at the interdomain region generates active MKP3 fragments that regulate ERK1/2 subcellular localization and function. J Mol Biol. 2012;420:128-38 pubmed publisher
    MAPK (MAP kinase) phosphatase 3 (DUSP6/MKP3) is a cytosolic MKP (MAPK phosphatase) that regulates negatively ERK1/2 downstream to growth factor or apoptotic signaling...
  5. Stewart A, Dowd S, Keyse S, McDonald N. Crystal structure of the MAPK phosphatase Pyst1 catalytic domain and implications for regulated activation. Nat Struct Biol. 1999;6:174-81 pubmed
    The crystal structure of the catalytic domain from the MAPK phosphatase Pyst1 (Pyst1-CD) has been determined at 2.35 A...
  6. Furukawa T, Sunamura M, Motoi F, Matsuno S, Horii A. Potential tumor suppressive pathway involving DUSP6/MKP-3 in pancreatic cancer. Am J Pathol. 2003;162:1807-15 pubmed
    We previously found frequent loss of heterozygosity at 12q21 and 12q22-q23.1 in primary pancreatic cancers, and the DUSP6/MKP-3 gene residing in this region at 12q22 lost its expression in the great majority of pancreatic cancer cell ..
  7. Whetzel A, Bolick D, Hedrick C. Sphingosine-1-phosphate inhibits high glucose-mediated ERK1/2 action in endothelium through induction of MAP kinase phosphatase-3. Am J Physiol Cell Physiol. 2009;296:C339-45 pubmed publisher
    ..Thus, one mechanism for the anti-inflammatory action of S1P in diabetic EC is inhibition of ERK1/2 phosphorylation through induction of MKP-3 expression via the S1P-S1P(1) receptor axis. ..
  8. Degl Innocenti D, Romeo P, Tarantino E, Sensi M, Cassinelli G, Catalano V, et al. DUSP6/MKP3 is overexpressed in papillary and poorly differentiated thyroid carcinoma and contributes to neoplastic properties of thyroid cancer cells. Endocr Relat Cancer. 2013;20:23-37 pubmed publisher
    ..RET/PTC, and TRK oncogenes upregulate the ERK1/2 pathway's attenuator cytoplasmic dual-phase phosphatase DUSP6/MKP3 in thyroid cells...
  9. Groom L, Sneddon A, Alessi D, Dowd S, Keyse S. Differential regulation of the MAP, SAP and RK/p38 kinases by Pyst1, a novel cytosolic dual-specificity phosphatase. EMBO J. 1996;15:3621-32 pubmed
    The Pyst1 and Pyst2 mRNAs encode closely related proteins, which are novel members of a family of dual-specificity MAP kinase phosphatases typified by CL100/MKP-1...
  10. Karlsson M, Mathers J, Dickinson R, Mandl M, Keyse S. Both nuclear-cytoplasmic shuttling of the dual specificity phosphatase MKP-3 and its ability to anchor MAP kinase in the cytoplasm are mediated by a conserved nuclear export signal. J Biol Chem. 2004;279:41882-91 pubmed
    ..Our results reinforce the idea that regulatory proteins such as MKP-3 may play a key role in the spatio-temporal regulation of MAP kinase activity. ..
  11. Arkell R, Dickinson R, Squires M, Hayat S, Keyse S, Cook S. DUSP6/MKP-3 inactivates ERK1/2 but fails to bind and inactivate ERK5. Cell Signal. 2008;20:836-43 pubmed publisher
    ..These include both nuclear (DUSP5) and cytoplasmic (DUSP6) enzymes...
  12. Zhang Y, Wu J, Wang Z. Mitogen-activated protein kinase (MAPK) phosphatase 3-mediated cross-talk between MAPKs ERK2 and p38alpha. J Biol Chem. 2011;286:16150-62 pubmed publisher
    MAPK phosphatase 3 (MKP3) is highly specific for ERK1/2 inactivation via dephosphorylation of both phosphotyrosine and phosphothreonine critical for enzymatic activation...
  13. Dowd S, Sneddon A, Keyse S. Isolation of the human genes encoding the pyst1 and Pyst2 phosphatases: characterisation of Pyst2 as a cytosolic dual-specificity MAP kinase phosphatase and its catalytic activation by both MAP and SAP kinases. J Cell Sci. 1998;111 ( Pt 22):3389-99 pubmed
    We have isolated the human genes encoding the Pyst1 (MKP-3) and Pyst2 (MKP-X) MAP kinase phosphatases...
  14. Rossig L, Haendeler J, Hermann C, Malchow P, Urbich C, Zeiher A, et al. Nitric oxide down-regulates MKP-3 mRNA levels: involvement in endothelial cell protection from apoptosis. J Biol Chem. 2000;275:25502-7 pubmed
    ..These data demonstrate that upstream of the S-nitrosylation of caspase-3, NO exerts additional antiapoptotic effects in endothelial cells, which rely on the down-regulation of MKP-3 mRNA. ..
  15. Marchetti S, Gimond C, Chambard J, Touboul T, Roux D, Pouyssegur J, et al. Extracellular signal-regulated kinases phosphorylate mitogen-activated protein kinase phosphatase 3/DUSP6 at serines 159 and 197, two sites critical for its proteasomal degradation. Mol Cell Biol. 2005;25:854-64 pubmed
    ..Here, we describe a novel posttranslational mechanism for regulating MKP-3/Pyst1/DUSP6, a member of the MKP family that is highly specific for extracellular signal-regulated kinase 1 and 2 (ERK1/..
  16. Xie J, Jiang Y, Jiang Y, Li C, Lim M, An O, et al. Super-Enhancer-Driven Long Non-Coding RNA LINC01503, Regulated by TP63, Is Over-Expressed and Oncogenic in Squamous Cell Carcinoma. Gastroenterology. 2018;154:2137-2151.e1 pubmed publisher
    ..Expression of LINC01503 in ESCC cell lines reduced ERK2 dephosphorylation by DUSP6, leading to activation of ERK signaling via MAPK...
  17. Mirmalek Sani S, Stokes P, Tare R, Ralph E, Inglis S, Hanley N, et al. Derivation of a novel undifferentiated human foetal phenotype in serum-free cultures with BMP-2. J Cell Mol Med. 2009;13:3541-55 pubmed publisher
    ..SC4MOL and SQLE), genes involved in morphogenesis (SOX15 and WIF1) and differentiation potential (C1orf19, CHSY-2,DUSP6, HMGCS1 and PPL)...
  18. Moulana F, Priyani A, De Silva M, Dassanayake R. BRAF-Oncogene-Induced Senescence and the Role of Thyroid-Stimulating Hormone Signaling in the Progression of Papillary Thyroid Carcinoma. Horm Cancer. 2018;9:1-11 pubmed publisher
    ..in levels of downstream enzymes such as manganese superoxide dismutase (MnSOD) and dual-specific phosphatase 6 (DUSP6) which eventually results in the production of oncogenic proteins such as c-Myc...
  19. Whittaker S, Barlow C, Martin M, Mancusi C, Wagner S, Self A, et al. Molecular profiling and combinatorial activity of CCT068127: A potent CDK2 and CDK9 inhibitor. Mol Oncol. 2017;: pubmed publisher
    ..CCT068127 caused a dramatic loss in expression of DUSP6 phosphatase, alongside elevated ERK phosphorylation and activation of MAPK pathway target genes...
  20. Wang L, Xia W, Chen H, Xiao Z. ΔNp63α modulates phosphorylation of p38 MAP kinase in regulation of cell cycle progression and cell growth. Biochem Biophys Res Commun. 2019;: pubmed publisher
    ..In addition, MAP Kinase Phosphatase 3 (MKP3) was responsible for ΔNp63α-mediated regulation of p38MAPK phosphorylation...
  21. Lösing P, Niturad C, Harrer M, Reckendorf C, Schätz T, Sinske D, et al. SRF modulates seizure occurrence, activity induced gene transcription and hippocampal circuit reorganization in the mouse pilocarpine epilepsy model. Mol Brain. 2017;10:30 pubmed publisher
    ..Upon SRF ablation, seizure evoked induction of dual specific phosphatases (Dusp5 and Dusp6) was reduced...
  22. Gupta S, M Redmond T, Meng F, Tidball A, Akil H, Watson S, et al. Fibroblast growth factor 2 regulates activity and gene expression of human post-mitotic excitatory neurons. J Neurochem. 2018;145:188-203 pubmed publisher
    ..FGF2-regulated genes previously identified in non-neuronal cell types were up-regulated (EGR1, ETV4, SPRY4, and DUSP6) as a result of chronic FGF2 treatment of siNeurons...
  23. Lv C, Wang H, Tong Y, Yin H, Wang D, Yan Z, et al. The function of BTG3 in colorectal cancer cells and its possible signaling pathway. J Cancer Res Clin Oncol. 2018;144:295-308 pubmed publisher
    ..YWHAB, and signal transducer and activator of transcription (STAT)3 protein levels, but downregulated RAP1A, DUSP6, and STAT1 protein expression, which was consistent with the genomic microarray data...
  24. Doraczynska Kowalik A, Nelke K, Pawlak W, Sasiadek M, Gerber H. Genetic Factors Involved in Mandibular Prognathism. J Craniofac Surg. 2017;28:e422-e431 pubmed publisher
    ..2. The following appear among candidate genes: MATN1, EPB41, growth hormone receptor, COL2A1, COL1A1, MYO1H, DUSP6, ARHGAP21, ADAMTS1, FGF23, FGFR2, TBX5, ALPL, HSPG2, EVC, EVC2, the HoxC gene cluster, insulin-like growth factor ..
  25. Plotnik J, Budka J, Ferris M, Hollenhorst P. ETS1 is a genome-wide effector of RAS/ERK signaling in epithelial cells. Nucleic Acids Res. 2014;42:11928-40 pubmed publisher
    ..cell migration genes, but also identified a surprising role for ETS1 in the repression of genes such as DUSP4, DUSP6 and SPRY4 that provide negative feedback to the RAS/ERK pathway...
  26. Shen C, Kim S, Trousil S, Frederick D, Piris A, Yuan P, et al. Loss of cohesin complex components STAG2 or STAG3 confers resistance to BRAF inhibition in melanoma. Nat Med. 2016;22:1056-61 pubmed publisher
    ..Loss of STAG2 inhibited CCCTC-binding-factor-mediated expression of dual specificity phosphatase 6 (DUSP6), leading to reactivation of mitogen-activated protein kinase (MAPK) signaling (via the MAPKs ERK1 and ERK2; ..
  27. Yeh C, Fan Y, Yang Y, Mann M. Atrial ERK1/2 activation in the embryo leads to incomplete Septal closure: a novel mouse model of atrial Septal defect. J Biomed Sci. 2017;24:89 pubmed publisher
    ..In an alternative transgenic aMEK1 model with elevated atrial MKP3 expression and corresponding suppression of increases in ERK1/2 phosphorylation, animals did not develop ASD...
  28. Lu M, Xu X, Xi B, Dai Q, Li C, Su L, et al. Molecular Network-Based Identification of Competing Endogenous RNAs in Thyroid Carcinoma. Genes (Basel). 2018;9: pubmed publisher
    ..was inferred to be significant for patients' survival with 34 associated ceRNAs, among which RUNX2, DUSP6 and SEMA3D are known oncogenes regulating cellular proliferation and differentiation in thyroid cancer...
  29. Ding Y, Wang C, Li X, Jiang Y, Mei P, Huang W, et al. Novel clinicopathological and molecular characterization of metanephric adenoma: a study of 28 cases. Diagn Pathol. 2018;13:54 pubmed publisher
    ..Highly expressed p16 and DUSP6 may have contributed to these results, which maintained MA as a benign renal tumor...
  30. Omarjee S, Jacquemetton J, Poulard C, Rochel N, Dejaegere A, Chebaro Y, et al. The molecular mechanisms underlying the ERα-36-mediated signaling in breast cancer. Oncogene. 2017;36:2503-2514 pubmed publisher
    ..Of note, the direct binding of ERα-36 to ERK2 prevents its dephosphorylation by MKP3 and enhances the downstream signaling...
  31. Bagnyukova T, Restifo D, Beeharry N, Gabitova L, Li T, Serebriiskii I, et al. DUSP6 regulates drug sensitivity by modulating DNA damage response. Br J Cancer. 2013;109:1063-71 pubmed publisher
    Dual specificity phosphatase 6 (DUSP6) is a member of a family of mitogen-activated protein kinase phosphatases that dephosphorylates and inhibits activated ERK1/2...
  32. Goedert L, Pereira C, Roszik J, Plaça J, Cardoso C, Chen G, et al. RMEL3, a novel BRAFV600E-associated long noncoding RNA, is required for MAPK and PI3K signaling in melanoma. Oncotarget. 2016;7:36711-36718 pubmed publisher
    ..RMEL3 knockdown led to downregulation of activators or effectors of these pathways, including FGF2, FGF3, DUSP6, ITGB3 and GNG2...
  33. Zhou B, Ritt D, Morrison D, Der C, Cox A. Protein Kinase CK2? Maintains Extracellular Signal-regulated Kinase (ERK) Activity in a CK2? Kinase-independent Manner to Promote Resistance to Inhibitors of RAF and MEK but Not ERK in BRAF Mutant Melanoma. J Biol Chem. 2016;291:17804-15 pubmed publisher
    ..We found that CK2? post-translationally regulates the ERK-specific phosphatase dual specificity phosphatase 6 (DUSP6) in a kinase dependent-manner, decreasing its abundance...
  34. Ma L, Bayram Y, McLaughlin H, Cho M, Krokosky A, Turner C, et al. De novo missense variants in PPP1CB are associated with intellectual disability and congenital heart disease. Hum Genet. 2016;135:1399-1409 pubmed
    ..Our data suggest that our heterozygous de novo PPP1CB pathogenic variants are associated with syndromic intellectual disability. ..
  35. Rodrigues B, Kuga G, Muñoz V, Gaspar R, Tavares M, Botezelli J, et al. Overexpression of Mitogen-activated protein kinase phosphatase-3 (MKP-3) reduces FoxO1 phosphorylation in mice hypothalamus. Neurosci Lett. 2017;659:14-17 pubmed publisher
    ..In the present study, we overexpressed the DUSP6 gene through an injection of adenovirus directly into the hypothalamic third ventricle of Swiss mice...
  36. Muda M, Boschert U, Dickinson R, Martinou J, Martinou I, Camps M, et al. MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase. J Biol Chem. 1996;271:4319-26 pubmed
  37. Bergholz J, Zhang Y, Wu J, Meng L, Walsh E, Rai A, et al. ?Np63? regulates Erk signaling via MKP3 to inhibit cancer metastasis. Oncogene. 2014;33:212-24 pubmed publisher
    ..We identified mitogen-activated protein (MAP) kinase phosphatase 3 (MKP3) as a downstream target of ?Np63? that is required for mediating these effects...
  38. Kaltenmeier C, Vollmer L, Vernetti L, Caprio L, Davis K, Korotchenko V, et al. A Tumor Cell-Selective Inhibitor of Mitogen-Activated Protein Kinase Phosphatases Sensitizes Breast Cancer Cells to Lymphokine-Activated Killer Cell Activity. J Pharmacol Exp Ther. 2017;361:39-50 pubmed publisher
    ..is devoid of developmental toxicity and restores defective MAPK activity caused by overexpression of DUSP1 and DUSP6 in mammalian cells. Here, we hypothesized that BCI-215 could selectively affect survival of transformed cells...
  39. Huang X, Liao W, Huang Y, Jiang M, Chen J, Wang M, et al. Neuroprotective effect of dual specificity phosphatase 6 against glutamate-induced cytotoxicity in mouse hippocampal neurons. Biomed Pharmacother. 2017;91:385-392 pubmed publisher
    Dual specificity phosphatase 6 (DUSP6), a member of the dual specificity protein phosphatase subfamily, can inactivate ERK1/2. However, its possible role in glutamate-induced oxidative cytotoxicity effects is not clear...
  40. Nakanishi Y, Mizuno H, Sase H, Fujii T, Sakata K, Akiyama N, et al. ERK Signal Suppression and Sensitivity to CH5183284/Debio 1347, a Selective FGFR Inhibitor. Mol Cancer Ther. 2015;14:2831-9 pubmed publisher
    ..efficacy in a collection of cell lines with the ERK signature and identified dual-specificity phosphatase 6 (DUSP6) as a candidate marker...
  41. Sharma N, Kubaczka C, Kaiser S, Nettersheim D, Mughal S, Riesenberg S, et al. Tpbpa-Cre-mediated deletion of TFAP2C leads to deregulation of Cdkn1a, Akt1 and the ERK pathway, causing placental growth arrest. Development. 2016;143:787-98 pubmed publisher
    ..5 results in growth arrest of the junctional zone. TFAP2C regulates its target genes Cdkn1a (previously p21) and Dusp6, which are involved in repression of MAPK signaling. Loss of TFAP2C reduces activation of ERK1/2 in the placenta...
  42. Ma Y, Tian S, He S, Chen Q, Wang Z, Xiao X, et al. The mechanism of action of FXR1P-related miR-19b-3p in SH-SY5Y. Gene. 2016;588:62-8 pubmed publisher
    ..We determined that miR-19b-3p could regulate the expression of not only USP32, RAB18 and Dusp6 but also FXR1, and FXR1 could in turn regulate the expression of miR-19b-3p...
  43. Parveen S, Bandhyopadhyay S, Das S, Majumdar S, Jawed J, Chowdhury B, et al. Mycobacterium indicus pranii (Mw)-mediated protection against visceral leishmaniasis by reciprocal regulation of host dual-specificity phosphatases. Int Immunol. 2016;28:585-595 pubmed publisher
    ..Here, we show that Mycobacterium indicus pranii (Mw), an immunomodulator, reciprocally regulates DUSP1 and DUSP6 through the TLR4 pathway...
  44. Ouyang P, Lin B, Du J, Pan H, Yu H, He R, et al. Global gene expression analysis of knockdown Triosephosphate isomerase (TPI) gene in human gastric cancer cell line MGC-803. Gene. 2018;647:61-72 pubmed publisher
    ..01), which contained common cancer-related genes, such as DUSP6, ETV5, IL6, PLAU, PPARG and HMGA2...
  45. Kim Y, Choi Y, Han J, Lee J, Soh E, Park S, et al. TSH signaling overcomes B-RafV600E-induced senescence in papillary thyroid carcinogenesis through regulation of DUSP6. Neoplasia. 2014;16:1107-20 pubmed publisher
    ..down-regulation of p-extracellular signal-regulated kinases 1/2 and up-regulation of dual specific phosphatase 6 (DUSP6) in the PTC with B-RafV600E mutation...
  46. Ham J, Oh E, Kim D, Choi S. Differential expression profiles and roles of inducible DUSPs and ERK1/2-specific constitutive DUSP6 and DUSP7 in microglia. Biochem Biophys Res Commun. 2015;467:254-60 pubmed publisher
    ..the inducible DUSPs which also dephosphorylate p38 MAPK and JNK in the major inflammatory pathways, constitutive DUSP6 and DUSP7 are specific to ERK1/2 and have not been studied in microglia and other immune cells to date...
  47. Koo J, Wang S, Kang N, Hur S, Bahk Y. Induction of MAP kinase phosphatase 3 through Erk/MAP kinase activation in three oncogenic Ras (H-, K- and N-Ras)-expressing NIH/3T3 mouse embryonic fibroblast cell lines. BMB Rep. 2016;49:370-5 pubmed
    ..In the present study, using three inducible Ras-expressing NIH/3T3 cell lines, we demonstrated that MKP3 upregulation requires the activation of the Erk1/2 pathway, which correlates with the shutdown of this pathway...
  48. Wu Y, Hwang Y, Perng W, Chian C, Ho C, Lee S, et al. CPEB4 and IRF4 expression in peripheral mononuclear cells are potential prognostic factors for advanced lung cancer. J Formos Med Assoc. 2017;116:114-122 pubmed publisher
    ..cDNA synthesis, and real-time polymerase chain reaction (PCR) for the expression profiling of eight genes: DUSP6, MMD, CPEB4, RNF4, STAT2, NF1, IRF4, and ZNF264...
  49. Noro R, Ishigame T, Walsh N, Shiraishi K, Robles A, Ryan B, et al. A Two-Gene Prognostic Classifier for Early-Stage Lung Squamous Cell Carcinoma in Multiple Large-Scale and Geographically Diverse Cohorts. J Thorac Oncol. 2017;12:65-76 pubmed publisher
    ..Dual specificity phosphatase 6 gene (DUSP6) and actinin alpha 4 gene (ACTN4) were associated with prognostic outcome in two independent patient cohorts...
  50. Wang T, Ren Y, Wang H, Yu H, Zhao Y. Association of Topoisomerase II (TOP2A) and Dual-Specificity Phosphatase 6 (DUSP6) Single Nucleotide Polymorphisms with Radiation Treatment Response and Prognosis of Lung Cancer in Han Chinese. Med Sci Monit. 2017;23:984-993 pubmed
    ..DNA topoisomerase II (TOP2A) are associated with chemotherapy resistance, whereas dual-specificity phosphatase 6 (DUSP6) negatively regulates members of the mitogen-activated protein (MAP) kinase superfamily to control cell ..
  51. Pourteymour S, Hjorth M, Lee S, Holen T, Langleite T, Jensen J, et al. Dual specificity phosphatase 5 and 6 are oppositely regulated in human skeletal muscle by acute exercise. Physiol Rep. 2017;5: pubmed publisher
    ..The two ERK1/2-specific MKPs, dual specificity phosphatase 5 (DUSP5) and DUSP6, were the most regulated MKPs in skeletal muscle after acute exercise...
  52. Li W, Song L, Ritchie A, Melton D. Increased levels of DUSP6 phosphatase stimulate tumourigenesis in a molecularly distinct melanoma subtype. Pigment Cell Melanoma Res. 2012;25:188-99 pubmed publisher
    The mitogen-activated protein kinase (MAPK) pathway is important in melanoma. In this pathway, DUSP6 phosphatase negatively controls the activation of extracellular signal-regulated (ERK) kinase...
  53. Morita K, Masamoto Y, Kataoka K, Koya J, Kagoya Y, Yashiroda H, et al. BAALC potentiates oncogenic ERK pathway through interactions with MEKK1 and KLF4. Leukemia. 2015;29:2248-56 pubmed publisher
    ..interaction with a scaffold protein MEK kinase-1 (MEKK1), which inhibits the interaction between ERK and MAP kinase phosphatase 3 (MKP3/DUSP6)...
  54. Carpio L, Bradley E, Westendorf J. Histone deacetylase 3 suppresses Erk phosphorylation and matrix metalloproteinase (Mmp)-13 activity in chondrocytes. Connect Tissue Res. 2017;58:27-36 pubmed publisher
    ..were hyperphosphorylated as a result of decreased expression and activity of the Erk1/2 specific phosphatase, Dusp6. Erk1/2 kinase inhibitors and Dusp6 adenoviruses reduced Mmp13 expression and partially rescued matrix production ..
  55. Leng Y, Ma Y, Li X, Chen R, Zeng P, Li X, et al. l-Homocysteine-induced cathepsin V mediates the vascular endothelial inflammation in hyperhomocysteinaemia. Br J Pharmacol. 2018;175:1157-1172 pubmed publisher
    ..Increased cathepsin V promoted the degradation of DUSP6 and DUSP7, phosphorylation and subsequent nuclear translocation of ERK1/2, phosphorylation of STAT1 and expression ..
  56. Mark J, Aubin R, Smith S, Hefford M. Inhibition of mitogen-activated protein kinase phosphatase 3 activity by interdomain binding. J Biol Chem. 2008;283:28574-83 pubmed publisher
    Mitogen-activated protein (MAP) kinase phosphatase 3 (MKP3) is a cytoplasmic dual specificity phosphatase that functions to attenuate signaling via dephosphorylation and subsequent deactivation of its substrate and allosteric regulator, ..
  57. Yang B, Tan Y, Sun H, Fan J, Tang Z, Ji Y. Higher intratumor than peritumor expression of DUSP6/MKP-3 is associated with recurrence after curative resection of hepatocellular carcinoma. Chin Med J (Engl). 2014;127:1211-7 pubmed
    ..b>DUSP6 is a cytoplasmic MKP that can inactivate ERK. DUSP6 has been implicated in the development of some tumors...
  58. Díaz García C, Agudo López A, Pérez C, Prieto García E, Iglesias L, Ponce S, et al. Prognostic value of dual-specificity phosphatase 6 expression in non-small cell lung cancer. Tumour Biol. 2015;36:1199-206 pubmed publisher
    Dual-specificity phosphatase 6 (DUSP6/MKP-3) is a mitogen-activated protein kinase phosphatase that regulates extracellular signal-regulated kinases (ERKs) activity via feedback mechanisms, with an increasingly recognized role in tumour ..
  59. Zhang H, Chi Y, Gao K, Zhang X, Yao J. p53 protein-mediated up-regulation of MAP kinase phosphatase 3 (MKP-3) contributes to the establishment of the cellular senescent phenotype through dephosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2). J Biol Chem. 2015;290:1129-40 pubmed publisher
    ..Impairment of ERK1/2 activation could be an important mechanism by which p53 controls cellular senescence. ..
  60. Sarközi R, Miller B, Pollack V, Feifel E, Mayer G, Sorokin A, et al. ERK1/2-driven and MKP-mediated inhibition of EGF-induced ERK5 signaling in human proximal tubular cells. J Cell Physiol. 2007;211:88-100 pubmed
    ..Expression of Ad-caMEK1 in HK-2 cells resulted in the upregulation of the dual-specificity phosphatases MKP-3/DUSP6, MKP-1/DUSP1, and DUSP5...
  61. Tang J, Niu J, Xu D, Li Z, Li Q, Chen J. Alteration of nuclear matrix-intermediate filament system and differential expression of nuclear matrix proteins during human hepatocarcinoma cell differentiation. World J Gastroenterol. 2007;13:2791-7 pubmed
    ..Meanwhile, 21 NM proteins changed remarkably during SMMC-7721 cell differentiation. Four proteins, i.e. mutant Pyst1, hypothetical protein, nucleophosmin 1, and LBP were downregulated, whereas four other proteins, eIF6, p44 subunit,..
  62. Mortensen O, Larsen M, Prasad B, Amara S. Genetic complementation screen identifies a mitogen-activated protein kinase phosphatase, MKP3, as a regulator of dopamine transporter trafficking. Mol Biol Cell. 2008;19:2818-29 pubmed publisher
    ..complementation screen in Xenopus oocytes to identify a mitogen-activated protein (MAP) kinase phosphatase, MKP3/Pyst1/DUSP6, as a molecule that inhibits protein kinase C-induced (PKC) internalization of transporters, resulting in ..
  63. Chiappinelli K, Rimel B, Massad L, Goodfellow P. Infrequent methylation of the DUSP6 phosphatase in endometrial cancer. Gynecol Oncol. 2010;119:146-50 pubmed publisher
    Dual-specificity phosphatase six (DUSP6, MKP3, or PYST1) dephosphorylates phosphotyrosine and phosphothreonine residues on ERK-2 (MAPK1) to inactivate the ERK-2 kinase...
  64. Zhou Y, Li G, Ren J, Wang L, Zhao J, Ning S, et al. Protection of CD4+ T cells from hepatitis C virus infection-associated senescence via ?Np63-miR-181a-Sirt1 pathway. J Leukoc Biol. 2016;100:1201-1211 pubmed
    ..We have previously shown a decline in miR-181a, which regulates CD4+ T cell responses via DUSP6 overexpression, in individuals with hepatitis C virus (HCV) infection...
  65. Li S, Hao G, Li J, Peng W, Geng X, Sun J. Comparative analysis of dual specificity protein phosphatase genes 1, 2 and 5 in response to immune challenges in Japanese flounder Paralichthys olivaceus. Fish Shellfish Immunol. 2017;68:368-376 pubmed publisher
    ..Our previous studies have shown the involvement of DUSP6 in regulating innate immunity in Japanese flounder Paralichthys olivaceus...
  66. Lee K, Ahn Y, Joo E, Chang J, Kim Y. The association of DUSP6 gene with schizophrenia and bipolar disorder: its possible role in the development of bipolar disorder. Mol Psychiatry. 2006;11:425-6 pubmed
  67. Piya S, Kim J, Bae J, Seol D, Moon A, Kim T. DUSP6 is a novel transcriptional target of p53 and regulates p53-mediated apoptosis by modulating expression levels of Bcl-2 family proteins. FEBS Lett. 2012;586:4233-40 pubmed publisher
    ..Dual specificity phosphatase 6 (DUSP6) is a cytosolic phosphatase that inactivates the extracellular-signal-regulated kinase 1/2 (ERK1/2)...
  68. Lee E, Chung K, Yang S, Park M, Min H, Kim S, et al. DNA methylation of MAPK signal-inhibiting genes in papillary thyroid carcinoma. Anticancer Res. 2013;33:4833-9 pubmed
    ..the mitogen-activated protein kinase (MAPK) signal-inhibiting genes dual-specificity phosphatase 4 (DUSP4) and 6 (DUSP6); and serpin peptidase inhibitor A member 5 (SERPINA5) in thyroid cancer...
  69. Wu Q, Liao Y, Lu Y, Wang Y, Lu J, Zeng Z, et al. Pharmacological inhibition of DUSP6 suppresses gastric cancer growth and metastasis and overcomes cisplatin resistance. Cancer Lett. 2018;412:243-255 pubmed publisher
    ..Here, we demonstrated that dual-specificity phosphatases 6 (DUSP6) was overexpressed in GC and predicted poor overall survival and progression-free survival...
  70. Kim H, Song M, Kwak I, Park T, Lim I. Constitutive induction of p-Erk1/2 accompanied by reduced activities of protein phosphatases 1 and 2A and MKP3 due to reactive oxygen species during cellular senescence. J Biol Chem. 2003;278:37497-510 pubmed
    ..were efficiently dephosphorylated in vitro by protein phosphatases 1 and 2A (PP1/2A) and MAPK phosphatase 3 (MKP3)...
  71. Chan D, Liu V, Tsao G, Yao K, Furukawa T, Chan K, et al. Loss of MKP3 mediated by oxidative stress enhances tumorigenicity and chemoresistance of ovarian cancer cells. Carcinogenesis. 2008;29:1742-50 pubmed publisher
    ..Intriguingly, the loss of MKP3 protein was associated with ubiquitination/proteosome degradation mediated by high intracellular reactive oxygen ..
  72. Zeliadt N, Mauro L, Wattenberg E. Reciprocal regulation of extracellular signal regulated kinase 1/2 and mitogen activated protein kinase phosphatase-3. Toxicol Appl Pharmacol. 2008;232:408-17 pubmed publisher
    ..Altogether, these results suggest that under the pressure of oncogenic Ras expression, MKP-3 reins in ERK1/2 by serving in ERK1/2-dependent negative feedback pathways. ..
  73. Nikopensius T, Saag M, Jagomagi T, Annilo T, Kals M, Kivistik P, et al. A missense mutation in DUSP6 is associated with Class III malocclusion. J Dent Res. 2013;92:893-8 pubmed publisher
    ..We identified a rare heterozygous missense mutation, c.545C>T (p.Ser182Phe), in the DUSP6 gene, a likely causal variant...
  74. Mishra A, Oulès B, Pisco A, Ly T, Liakath Ali K, Walko G, et al. A protein phosphatase network controls the temporal and spatial dynamics of differentiation commitment in human epidermis. elife. 2017;6: pubmed publisher
    ..Cell detachment induces several protein phosphatases, five of which - DUSP6, PPTC7, PTPN1, PTPN13 and PPP3CA - promote differentiation by negatively regulating ERK MAPK and positively ..
  75. Smith A, Price C, Cullen M, Muda M, King A, Ozanne B, et al. Chromosomal localization of three human dual specificity phosphatase genes (DUSP4, DUSP6, and DUSP7). Genomics. 1997;42:524-7 pubmed
    ..The genes were localized to three different chromosomes, MKP2 (DUSP4) to 8p11-p12, MKP3 (DUSP6) to 12q22-q23, and MKPX (DUSP7) to 3p21...
  76. Geetha N, Mihaly J, Stockenhuber A, Blasi F, Uhrin P, Binder B, et al. Signal integration and coincidence detection in the mitogen-activated protein kinase/extracellular signal-regulated kinase (ERK) cascade: concomitant activation of receptor tyrosine kinases and of LRP-1 leads to sustained ERK phosphorylation via down. J Biol Chem. 2011;286:25663-74 pubmed publisher
    ..of phospho-ERK was accounted for by enhanced proteasomal degradation of dual specificity phosphatases DUSP1 and DUSP6, which precluded dephosphorylation of cytosolic ERK...
  77. Yang D, Xie P, Liu Z. Ischemia/reperfusion-induced MKP-3 impairs endothelial NO formation via inactivation of ERK1/2 pathway. PLoS ONE. 2012;7:e42076 pubmed publisher
  78. Hrustanovic G, Olivas V, Pazarentzos E, Tulpule A, Asthana S, Blakely C, et al. RAS-MAPK dependence underlies a rational polytherapy strategy in EML4-ALK-positive lung cancer. Nat Med. 2015;21:1038-47 pubmed publisher
    ..number of copies of the gene encoding wild-type K-RAS (KRAS(WT)) or decreased expression of the MAPK phosphatase DUSP6 promoted resistance to ALK inhibitors in vitro, and each was associated with resistance to ALK inhibitors in ..
  79. Pfuhlmann K, Pfluger P, Schriever S, Müller T, Tschop M, Stemmer K. Dual specificity phosphatase 6 deficiency is associated with impaired systemic glucose tolerance and reversible weight retardation in mice. PLoS ONE. 2017;12:e0183488 pubmed publisher
    Here, we aimed to investigate the potential role of DUSP6, a dual specificity phosphatase, that specifically inactivates extracellular signal-regulated kinase (ERK), for the regulation of body weight and glucose homeostasis...
  80. Wong V, Chen H, Ko J, Chan K, Chan Y, Law S, et al. Tumor suppressor dual-specificity phosphatase 6 (DUSP6) impairs cell invasion and epithelial-mesenchymal transition (EMT)-associated phenotype. Int J Cancer. 2012;130:83-95 pubmed publisher
    Suppressive effects of DUSP6 in tumorigenesis and EMT-associated properties were observed...
  81. Guo Q, Zhang H, Zhao X, Fu Y, Zhang J, Li M. Loss of expressions of Dusp6, Sprouty4, and Sef, negative regulators of FGF2/ERK1/2 signaling, in the endometrium of women with adenomyosis. Int J Gynecol Pathol. 2014;33:288-97 pubmed publisher
    Dual-specificity phosphatase 6 (Dusp6), Sprouty4, and similar expression to FGF (Sef) are negative modulators of FGF2/ERK1/2 signaling...
  82. Wittig Blaich S, Wittig R, Schmidt S, Lyer S, Bewerunge Hudler M, Gronert Sum S, et al. Systematic screening of isogenic cancer cells identifies DUSP6 as context-specific synthetic lethal target in melanoma. Oncotarget. 2017;8:23760-23774 pubmed publisher
    ..method and we proved its potential to identify new drug targets via the identification of the tumor suppressor DUSP6 as potential synthetic lethal target in melanoma cell lines with BRAF V600E mutations and high DUSP6 expression.
  83. Mortensen O, Larsen M, Amara S. MAP Kinase Phosphatase 3 (MKP3) Preserves Norepinephrine Transporter Activity by Modulating ERK1/2 Kinase-Mediated Gene Expression. Front Cell Neurosci. 2017;11:253 pubmed publisher
    ..Previously we identified a MAP kinase phosphatase 3 (MKP3), as an important modulator of protein kinase C (PKC) mediated internalization of the related ..
  84. Buffet C, Hecale Perlemoine K, Bricaire L, Dumont F, Baudry C, Tissier F, et al. DUSP5 and DUSP6, two ERK specific phosphatases, are markers of a higher MAPK signaling activation in BRAF mutated thyroid cancers. PLoS ONE. 2017;12:e0184861 pubmed publisher
    ..by Dual Specificity Phosphatases (DUSPs), especially two ERK-specific DUSPs, DUSP5 (nuclear) and DUSP6 (cytosolic). These negative MAPK regulators may play a role in thyroid carcinogenesis...
  85. Wu X, Miao J, Jiang J, Liu F. Analysis of methylation profiling data of hyperplasia and primary and metastatic endometrial cancers. Eur J Obstet Gynecol Reprod Biol. 2017;217:161-166 pubmed publisher
    ..g. PAX6 and INSR) and 6 common hypomethylated DMGs (e.g. PRDM8, KLHL14, and DUSP6) were found. For primary-hyperplasia DMG set and metastasis-hyperplasia DMG set, 527 common DMGs were found...
  86. Wang Z, Reinach P, Zhang F, Vellonen K, Urtti A, Turner H, et al. DUSP5 and DUSP6 modulate corneal epithelial cell proliferation. Mol Vis. 2010;16:1696-704 pubmed
    ..Three DUSPs, DUSP1, DUSP5, and DUSP6, are overexpressed in ocular surface side population stem cells (SPSCs)...
  87. Lee H, Kim J, Huang S, Park S, Kim D, Kim D, et al. Differential expression of DUSP6 with expression of ERK and Ki-67 in non-small cell lung carcinoma. Pathol Res Pract. 2011;207:428-32 pubmed publisher
    Dual specificity phosphatase 6 (DUSP6) is a member of the MAP kinase phophatase family. DUSP6 inactivates extracellular signal-regulated kinase (ERK), belonging to the MAP kinase family, and can act in tumor suppressive pathways...
  88. Jing J, Greshock J, Holbrook J, Gilmartin A, Zhang X, McNeil E, et al. Comprehensive predictive biomarker analysis for MEK inhibitor GSK1120212. Mol Cancer Ther. 2012;11:720-9 pubmed publisher
    ..We identified a single gene DUSP6, whose expression was associated with sensitivity to GSK1120212 and lack of expression associated with resistance ..
  89. Zhai X, Han Q, Shan Z, Qu X, Guo L, Zhou Y. Dual specificity phosphatase 6 suppresses the growth and metastasis of prostate cancer cells. Mol Med Rep. 2014;10:3052-8 pubmed publisher
    Dual specificity phosphatase 6 (DUSP6) is expressed at low levels in numerous types of human cancer. The loss of DUSP6 plays a pivotal role in tumor progression; however, the role of DUSP6 in prostate cancer remains unclear...
  90. Zhang H, Yan L, Bai Y, Li C, Guo Q, Wang C, et al. Dual-specificity phosphatase 6 predicts the sensitivity of progestin therapy for atypical endometrial hyperplasia. Gynecol Oncol. 2015;136:549-53 pubmed publisher
    We previously found that Dual-specificity phosphatase 6 (Dusp6) over-expression enhanced the growth-promoting effect of estrogen in endometrial adenocarcinoma cells...
  91. Xie X, Nie X, Wu J, Zhang F, Zhao L, Lin Y, et al. Smooth muscle 22α facilitates angiotensin II-induced signaling and vascular contraction. J Mol Med (Berl). 2015;93:547-58 pubmed publisher
    ..of ERK1/2 activity was associated with increased expression of mitogen-activated protein kinase phosphatase 3 (MKP3). Inhibition of MKP3 activity rescued ERK1/2 activity...
  92. Lu C, Liu X, Zhang C, Gong H, Wu J, Wang Z. Structural and Dynamic Insights into the Mechanism of Allosteric Signal Transmission in ERK2-Mediated MKP3 Activation. Biochemistry. 2017;56:6165-6175 pubmed publisher
    ..combination of experimental and computational techniques to elucidate the molecular mechanism for the ERK2-induced MKP3 activation...