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Gene Review

Dusp6  -  dual specificity phosphatase 6

Rattus norvegicus

Synonyms: Dual specificity protein phosphatase 6, MAP kinase phosphatase 3, MKP-3, Mitogen-activated protein kinase phosphatase 3, Mkp3
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Disease relevance of Dusp6

  • The neuroprotective effect of the MKP3 C293S mutant, which enhances ERK1/2 phosphorylation but blocks its nuclear translocation, demonstrates the necessity for active ERK1/2 nuclear localization for oxidative toxicity in neurons [1].

High impact information on Dusp6


Biological context of Dusp6

  • Despite the presence of MKP-3, ERK activity can be further stimulated by NGF, but it fails to translocate into the nucleus and consequently to induce immediate-early gene transcription [6].
  • These results suggest that MKP-1 and MKP-3 may be involved in the early steps of apoptosis in vivo in rat olfactory neuroepithelium [7].

Associations of Dusp6 with chemical compounds

  • Consistent with a role mediating inhibition of PC12 cell MAP kinases, NGF-stimulated ERK2 activation was suppressed considerably following pretreatment with fibroblast growth factor and 9-cis-retinal, two additional differentiation factors found to induce powerfully MKP-3 expression [5].
  • We have studied expression of four DS-PTPs (MKP-1, MKP-X, MKP-3 and B23) in rat brain and examined changes during post-natal development and following kainic acid induced seizure activity [8].
  • Following kainate treatment, MKP-1, MKP-3 and B23 all exhibit striking changes in expression within hippocampal subfields CA1-3 and dentate gyrus [8].

Other interactions of Dusp6

  • 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 non-nuclear compartments during essential stages of NGF-mediated PC12 differentiation [5].
  • Induction of the mitogen-activated protein kinase phosphatase MKP3 by nerve growth factor in differentiating PC12 [5].
  • The sequence of these 23 individual clones revealed that two clones were identical to the rat dsPTP, MKP-3, and the other 21 clones were identical to the rat dsPTP, MKP-1 [7].
  • We have now employed cDNA representational difference analysis to identify four genes (activity-regulated cytoskeletal protein, collagenase 1, plasminogen activator inhibitor-1, and VH6/MKP-3) as genes preferentially induced withing 4 hours by NGF in PC12 cells [9].

Analytical, diagnostic and therapeutic context of Dusp6


  1. Reversible oxidation of ERK-directed protein phosphatases drives oxidative toxicity in neurons. Levinthal, D.J., Defranco, D.B. J. Biol. Chem. (2005) [Pubmed]
  2. Electroconvulsive seizures increase the expression of MAP kinase phosphatases in limbic regions of rat brain. Kodama, M., Russell, D.S., Duman, R.S. Neuropsychopharmacology (2005) [Pubmed]
  3. 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. Takaki, M., Ujike, H., Kodama, M., Takehisa, Y., Nakata, K., Kuroda, S. J. Neurochem. (2001) [Pubmed]
  4. Modification of representational difference analysis applied to the isolation of forskolin-regulated genes from Schwann cells. Bermingham, J.R., Shumas, S., Whisenhunt, T., Rosenfeld, M.G., Scherer, S.S. J. Neurosci. Res. (2001) [Pubmed]
  5. Induction of the mitogen-activated protein kinase phosphatase MKP3 by nerve growth factor in differentiating PC12. Camps, M., Chabert, C., Muda, M., Boschert, U., Gillieron, C., Arkinstall, S. FEBS Lett. (1998) [Pubmed]
  6. Abrogation of nerve growth factor-induced terminal differentiation by ret oncogene involves perturbation of nuclear translocation of ERK. Colucci-D'Amato, G.L., D'Alessio, A., Califano, D., Cali, G., Rizzo, C., Nitsch, L., Santelli, G., de Franciscis, V. J. Biol. Chem. (2000) [Pubmed]
  7. Identification of dual specificity phosphatases induced by olfactory bulbectomy in rat olfactory neuroepithelium. Ishibashi, T., Shinogami, M., Ishimoto, S., Nibu, K., Suzuki, M., Kaga, K. Brain Res. (2001) [Pubmed]
  8. Regulated expression of dual specificity protein phosphatases in rat brain. Boschert, U., Dickinson, R., Muda, M., Camps, M., Arkinstall, S. Neuroreport (1998) [Pubmed]
  9. Identification of genes preferentially induced by nerve growth factor versus epidermal growth factor in PC12 pheochromocytoma cells by means of representational difference analysis. Vician, L., Basconcillo, R., Herschman, H.R. J. Neurosci. Res. (1997) [Pubmed]
  10. Map kinase phosphatases (MKP's) are early responsive genes during induction of cerulein hyperstimulation pancreatitis. Höfken, T., Keller, N., Fleischer, F., Göke, B., Wagner, A.C. Biochem. Biophys. Res. Commun. (2000) [Pubmed]
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