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Gene Review

Dusp4  -  dual specificity phosphatase 4

Rattus norvegicus

Synonyms: Dual specificity protein phosphatase 4, MAP kinase phosphatase 2, MKP-2, Mitogen-activated protein kinase phosphatase 2, Mkp-2, ...
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Disease relevance of Dusp4


High impact information on Dusp4

  • RA up-regulated the expression level of MAP kinase phosphatase-1 (MKP-1) and MKP-2, and the time course was correlated with the inhibitory effect of RA on activation of MAP kinases [3].
  • Mitogen-activated protein (MAP) kinase phosphatase-1 (MKP-1) and MKP-2 are two members of a recently described family of dual specificity phosphatases that are capable of dephosphorylating p42/p44MAPK [4].
  • To analyze the contribution of the MAP kinase cascade to MKP-1 and MKP-2 induction, we examined CCL39 cells transformed with either v-ras or a constitutively active direct upstream activator of MAP kinase, mitogen-activated protein kinase kinase-1 (MKK-1; MKK-1(SD/SD) mutant) [4].
  • Overexpression of MKP-1 or MKP-2 inhibits MAP kinase-dependent intracellular signaling events and fibroblast proliferation [4].
  • We report the identification of a second widely expressed MKP, termed MKP-2, isolated from PC12 cells [5].

Biological context of Dusp4

  • MKP-2 differed from MKP-1 in its tissue distribution and in its extent of induction by growth factors and agents that induce cellular stress, suggesting that these MKPs may have distinct physiological functions [5].
  • The MKP-2 mRNA level was increased with expression of malignant phenotypes in hepatomas [2].

Anatomical context of Dusp4

  • In contrast, MKP2 is induced mainly in the dentate gyrus and MKP3 is preferentially increased in the CA1 and CA3 cell layers [6].
  • MAP kinase phosphatase-2 (MKP-2) is a member of a family of dual specificity phosphatases (DSPs) that function in both the cytosol and nucleus to inactivate the MAP kinases [7].

Associations of Dusp4 with chemical compounds


Other interactions of Dusp4


  1. The I(1)-imidazoline receptor in PC12 pheochromocytoma cells reverses NGF-induced ERK activation and induces MKP-2 phosphatase. Edwards, L., Ernsberger, P. Brain Res. (2003) [Pubmed]
  2. The characteristic gene expressions of MAPK phosphatases 1 and 2 in hepatocarcinogenesis, rat ascites hepatoma cells, and regenerating rat liver. Yokoyama, A., Karasaki, H., Urushibara, N., Nomoto, K., Imai, Y., Nakamura, K., Mizuno, Y., Ogawa, K., Kikuchi, K. Biochem. Biophys. Res. Commun. (1997) [Pubmed]
  3. Mitogen-activated protein kinases and mitogen-activated protein kinase phosphatases mediate the inhibitory effects of all-trans retinoic acid on the hypertrophic growth of cardiomyocytes. Palm-Leis, A., Singh, U.S., Herbelin, B.S., Olsovsky, G.D., Baker, K.M., Pan, J. J. Biol. Chem. (2004) [Pubmed]
  4. The dual specificity mitogen-activated protein kinase phosphatase-1 and -2 are induced by the p42/p44MAPK cascade. Brondello, J.M., Brunet, A., Pouysségur, J., McKenzie, F.R. J. Biol. Chem. (1997) [Pubmed]
  5. A novel mitogen-activated protein kinase phosphatase. Structure, expression, and regulation. Misra-Press, A., Rim, C.S., Yao, H., Roberson, M.S., Stork, P.J. J. Biol. Chem. (1995) [Pubmed]
  6. 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]
  7. Disruption of two putative nuclear localization sequences is required for cytosolic localization of mitogen-activated protein kinase phosphatase-2. Sloss, C.M., Cadalbert, L., Finn, S.G., Fuller, S.J., Plevin, R. Cell. Signal. (2005) [Pubmed]
  8. Activation of mitogen-activated protein kinase phosphatase 2 by gonadotropin-releasing hormone. Zhang, T., Mulvaney, J.M., Roberson, M.S. Mol. Cell. Endocrinol. (2001) [Pubmed]
  9. Sleep deprivation impairs spatial memory and decreases extracellular signal-regulated kinase phosphorylation in the hippocampus. Guan, Z., Peng, X., Fang, J. Brain Res. (2004) [Pubmed]
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