Gene Symbol: Dusp6
Description: dual specificity phosphatase 6
Alias: Mkp3, dual specificity protein phosphatase 6, MAP kinase phosphatase 3, MKP-3, mitogen-activated protein kinase phosphatase 3
Species: rat
Products:     Dusp6

Top Publications

  1. Landry R, Martinez E, DeLeo J, Romero Sandoval E. Spinal cannabinoid receptor type 2 agonist reduces mechanical allodynia and induces mitogen-activated protein kinase phosphatases in a rat model of neuropathic pain. J Pain. 2012;13:836-48 pubmed publisher
    ..A cannabinoid type 2 receptor agonist, JWH015, reduced neuropathic allodynia in rats by reducing MAPK phosphorylation and inducing spinal MAPK phosphatases 1 and 3, the major regulators of MAPKs. ..
  2. 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
    ..Pyst2 binds p42 MAP kinase in vivo and both MAP kinase binding and substrate selectivity correlate with the ability of different recombinant MAP and SAP kinases to cause catalytic activation of the Pyst2 phosphatase in vitro. ..
  3. Höfken T, Keller N, Fleischer F, Goke B, Wagner A. Map kinase phosphatases (MKP's) are early responsive genes during induction of cerulein hyperstimulation pancreatitis. Biochem Biophys Res Commun. 2000;276:680-5 pubmed
    ..Interestingly, inhibition of MKP-1 expression by Ro-31-8220 maximally induced activation of JNK but not of p38 and ERK in acutely isolated acini. These effects indicate that JNK may indeed be a preferred MKP-1 substrate in vivo. ..
  4. Pacitto S, Uetrecht J, Boutros P, Popovic M. Changes in gene expression induced by tienilic Acid and sulfamethoxazole: testing the danger hypothesis. J Immunotoxicol. 2007;4:253-66 pubmed publisher
    ..factor 1, macrophage stimulating protein 1), cytotoxicity (caspase-12), and liver regeneration (p27(Kip1), DUSP6, serine dehyratase, spectrin beta II, inhibin beta(A))...
  5. Takaki M, Ujike H, Kodama M, Takehisa Y, Nakata K, Kuroda S. Two kinds of mitogen-activated protein kinase phosphatases, MKP-1 and MKP-3, are differentially activated by acute and chronic methamphetamine treatment in the rat brain. J Neurochem. 2001;79:679-88 pubmed
  6. Wang H, Cheng Z, Malbon C. Overexpression of mitogen-activated protein kinase phosphatases MKP1, MKP2 in human breast cancer. Cancer Lett. 2003;191:229-37 pubmed
    ..Suppression of MKP activity therapeutically may enable the expression of the pro-apoptotic signals from JNK in malignant cells. ..
  7. Johnson K, Hensley J, Kelso M, Wallace D, Gaido K. Mapping gene expression changes in the fetal rat testis following acute dibutyl phthalate exposure defines a complex temporal cascade of responding cell types. Biol Reprod. 2007;77:978-89 pubmed
    ..1 to 500 mg/kg body weight. Twelve genes (Ctgf, Cxcl10, Dusp6, Edn1, Egr1, Fos, Ier3, Junb, Nr4a1, Stc1, Thbs1, and Tnfrsf12a) were identified with increased expression by 1-3 ..
  8. Kondoh K, Nishida E. Regulation of MAP kinases by MAP kinase phosphatases. Biochim Biophys Acta. 2007;1773:1227-37 pubmed
    ..Here we focus on recent findings regarding regulation and function of the MKP family members as physiological regulators of MAPK signaling. ..
  9. 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

More Information


  1. Mortensen O. MKP3 eliminates depolarization-dependent neurotransmitter release through downregulation of L-type calcium channel Cav1.2 expression. Cell Calcium. 2013;53:224-30 pubmed publisher
    ..of the negative regulator of mitogen-activated protein kinase (MAPK) signaling the MAPK phosphatase MKP3/DUSP6 eliminates depolarization-dependent release of dopamine in rat PC12 cells...
  2. Srivastava N, Sudan R, Saha B. CD40-modulated dual-specificity phosphatases MAPK phosphatase (MKP)-1 and MKP-3 reciprocally regulate Leishmania major infection. J Immunol. 2011;186:5863-72 pubmed publisher
    ..The findings reveal a novel parasite-devised immune evasion strategy and an effective target to redirect CD40-regulated immune responses. ..
  3. Mourey R, Vega Q, Campbell J, Wenderoth M, Hauschka S, Krebs E, et al. A novel cytoplasmic dual specificity protein tyrosine phosphatase implicated in muscle and neuronal differentiation. J Biol Chem. 1996;271:3795-802 pubmed
    ..rVH6 protein localizes to the cytoplasm and is the first dsPTP to be localized outside the nucleus. This novel subcellular localization may expose rVH6 to potential substrates that differ from nuclear dsPTPs substrates. ..
  4. NDong C, Landry R, Saha M, Romero Sandoval E. Mitogen-activated protein kinase (MAPK) phosphatase-3 (MKP-3) displays a p-JNK-MAPK substrate preference in astrocytes in vitro. Neurosci Lett. 2014;575:13-8 pubmed publisher
    ..Our results indicate also that astrocytic immune functions can be modulated by MKP-3 induction, a strategy that could be beneficial in neurological conditions in which astrocytes play a pathophysiological role, i.e. persistent pain. ..
  5. Zhou B, Zhang J, Liu S, Reddy S, Wang F, Zhang Z. Mapping ERK2-MKP3 binding interfaces by hydrogen/deuterium exchange mass spectrometry. J Biol Chem. 2006;281:38834-44 pubmed
    ERK2, a prototypic member of the MAPK family, plays a central role in regulating cell growth and differentiation. MKP3, an ERK2-specific phosphatase, terminates ERK2 signaling...
  6. Kodama M, Russell D, Duman R. Electroconvulsive seizures increase the expression of MAP kinase phosphatases in limbic regions of rat brain. Neuropsychopharmacology. 2005;30:360-71 pubmed
    ..In the present study, we analyzed the expression of the MKP1, MKP2, and MKP3 isoforms in rat brain after electroconvulsive seizure (ECS), considered the most effective treatment for depression...
  7. Soriano M, Tessier M, Certa U, Gill R. Parallel gene expression monitoring using oligonucleotide probe arrays of multiple transcripts with an animal model of focal ischemia. J Cereb Blood Flow Metab. 2000;20:1045-55 pubmed
    ..This represented the first example of using high density oligonucleotide probe arrays in studying the expression of many genes in parallel and in discrete brain regions after focal ischemia. ..
  8. 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. ..
  9. Muda M, Theodosiou A, Gillieron C, Smith A, Chabert C, Camps M, et al. The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity. J Biol Chem. 1998;273:9323-9 pubmed
    ..Together, these observations suggest that the physiological specificity of MKP-3 for inactivation of ERK family MAP kinases reflects tight substrate binding by its N-terminal domain. ..
  10. Castelli M, Camps M, Gillieron C, Leroy D, Arkinstall S, Rommel C, et al. MAP kinase phosphatase 3 (MKP3) interacts with and is phosphorylated by protein kinase CK2alpha. J Biol Chem. 2004;279:44731-9 pubmed
    ..Although ERK2 activity is regulated by its phosphorylation state, MKP3 is regulated by physical interaction with ERK2, independent of its enzymatic activity (Camps, M., Nichols, A...
  11. Camps M, Chabert C, Muda M, Boschert U, Gillieron C, Arkinstall S. Induction of the mitogen-activated protein kinase phosphatase MKP3 by nerve growth factor in differentiating PC12. FEBS Lett. 1998;425:271-6 pubmed
    ..Given the clear cytosolic localization of MKP3 in PC12 cells and sympathetic neurons, these results suggest a critical role for inactivating ERK MAP kinases in ..
  12. Donaubauer E, Law N, Hunzicker Dunn M. Follicle-Stimulating Hormone (FSH)-dependent Regulation of Extracellular Regulated Kinase (ERK) Phosphorylation by the Mitogen-activated Protein (MAP) Kinase Phosphatase MKP3. J Biol Chem. 2016;291:19701-12 pubmed publisher
    ..Treatment with MAP kinase phosphatase (MKP3, DUSP6) inhibitors increased ERK(Thr(202)/Tyr(204)) phosphorylation in the absence of FSH to levels comparable with ERK ..
  13. Bowen J, Gibson R, Cummins A, Tyskin A, Keefe D. Irinotecan changes gene expression in the small intestine of the rat with breast cancer. Cancer Chemother Pharmacol. 2007;59:337-48 pubmed
    ..The common pathway of chemotherapy- and radiotherapy-induced damage, which utilises the caspase-cascade, may be a useful target to prevent apoptosis following cancer treatment. ..
  14. 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
  15. 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...
  16. Maillet M, Purcell N, Sargent M, York A, Bueno O, Molkentin J. DUSP6 (MKP3) null mice show enhanced ERK1/2 phosphorylation at baseline and increased myocyte proliferation in the heart affecting disease susceptibility. J Biol Chem. 2008;283:31246-55 pubmed publisher
    ..dephosphorylation plays in vivo through targeted disruption of the gene encoding dual-specificity phosphatase 6 (Dusp6) in the mouse...
  17. 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. ..
  18. Domercq M, Alberdi E, Sánchez Gómez M, Ariz U, Perez Samartin A, Matute C. Dual-specific phosphatase-6 (Dusp6) and ERK mediate AMPA receptor-induced oligodendrocyte death. J Biol Chem. 2011;286:11825-36 pubmed publisher
    ..Here, using microarray analysis and quantitative PCR, we observed that dual-specific phosphatase-6 (Dusp6), an extracellular regulated kinase-specific phosphatase, is up-regulated in oligodendrocyte cultures as well as ..
  19. Saha M, Skopelja S, Martinez E, Alvarez D, Liponis B, Romero Sandoval E. Spinal mitogen-activated protein kinase phosphatase-3 (MKP-3) is necessary for the normal resolution of mechanical allodynia in a mouse model of acute postoperative pain. J Neurosci. 2013;33:17182-7 pubmed publisher