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Gene Review

DUSP4  -  dual specificity phosphatase 4

Homo sapiens

Synonyms: Dual specificity protein phosphatase 4, Dual specificity protein phosphatase hVH2, HVH2, MAP kinase phosphatase 2, MKP-2, ...
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Disease relevance of DUSP4

  • Overexpression of mitogen-activated protein kinase phosphatases MKP1, MKP2 in human breast cancer [1].
  • Antibody activity to herpesvirus hominis type 2 (HVH-2) in 151 women cured of cervical carcinoma (60 in situ, 91 invasive) and in 106 controls differed significantly, especially between the in situ (73%) and control (17%) groups [2].
  • Our data further supported the association between HVH-2 and cervical anaplasia and indicated that CMV may also be implicated in its etiology [2].
  • Taxonomic analysis of four selected strains based on 16S rRNA similarity examinations revealed two Gordonia sp. strains, VH2 and Kb2, and one Mycobacterium fortuitum strain, NF4, belonging to the first group as well as one Micromonospora aurantiaca strain, W2b, belonging to the second group [3].
  • Linkage without a population association suggests that a gene encoded on 14q confers susceptibility to multiple sclerosis, although this is not any of the existing VH-2 polymorphisms [4].

High impact information on DUSP4


Biological context of DUSP4


Anatomical context of DUSP4


Associations of DUSP4 with chemical compounds

  • Through site-directed mutagenesis, we defined the ERK/p38-binding site as a cluster of arginine residues in the NH(2)-terminal domain of MKP-2 [9].
  • We demonstrate that Flag-WT-MKP-2 is able to rescue cells from apoptotic commitment when subjected to UV-C or cisplatin treatment [10].
  • The levels of a dual specificity tyrosine phosphatase, MKP2, were significantly decreased in cerebellar vermis (1716 +/- 465 versus 2372 +/- 429 arbitrary units, U = 12, p < .02) from schizophrenic patients [15].
  • We found that both inhibited the increase in expression of many of the genes, including IL-2 and MKP-2, that were induced early after stimulation of lymphocytes with phorbol myristate acetate and ionomycin [16].
  • Thereby, strains VH2, Kb2, and NF4 directly adhered to and merged into the rubber material, while strain W2b produced mycelial corridors, especially on the surface of IR [3].

Regulatory relationships of DUSP4

  • However, MKP-2 is surprisingly only able to deactivate JNK in vivo [10].

Other interactions of DUSP4


Analytical, diagnostic and therapeutic context of DUSP4


  1. Overexpression of mitogen-activated protein kinase phosphatases MKP1, MKP2 in human breast cancer. Wang, H.Y., Cheng, Z., Malbon, C.C. Cancer Lett. (2003) [Pubmed]
  2. Herpesvirus antibodies and antigens in patients with cervical anaplasia and in controls. Pacsa, A.S., Kummerländer, L., Pejtsik, B., Pali, K. J. Natl. Cancer Inst. (1975) [Pubmed]
  3. Biodegradation of cis-1,4-polyisoprene rubbers by distinct actinomycetes: microbial strategies and detailed surface analysis. Linos, A., Berekaa, M.M., Reichelt, R., Keller, U., Schmitt, J., Flemming, H.C., Kroppenstedt, R.M., Steinbüchel, A. Appl. Environ. Microbiol. (2000) [Pubmed]
  4. Susceptibility to multiple sclerosis and the immunoglobulin heavy chain variable region. Wood, N.W., Sawcer, S.J., Kellar-Wood, H.F., Holmans, P., Clayton, D., Robertson, N., Compston, D.A. J. Neurol. (1995) [Pubmed]
  5. Analysis of genetic variation reveals human immunoglobulin VH-region gene organization. Walter, M.A., Cox, D.W. Am. J. Hum. Genet. (1988) [Pubmed]
  6. Inactivation of dual-specificity phosphatases is involved in the regulation of extracellular signal-regulated kinases by heat shock and hsp72. Yaglom, J., O'Callaghan-Sunol, C., Gabai, V., Sherman, M.Y. Mol. Cell. Biol. (2003) [Pubmed]
  7. Mitogen-activated protein kinase phosphatase 2: a novel transcription target of p53 in apoptosis. Shen, W.H., Wang, J., Wu, J., Zhurkin, V.B., Yin, Y. Cancer Res. (2006) [Pubmed]
  8. Isolation and characterization of a novel dual specific phosphatase, HVH2, which selectively dephosphorylates the mitogen-activated protein kinase. Guan, K.L., Butch, E. J. Biol. Chem. (1995) [Pubmed]
  9. Discordance between the binding affinity of mitogen-activated protein kinase subfamily members for MAP kinase phosphatase-2 and their ability to activate the phosphatase catalytically. Chen, P., Hutter, D., Yang, X., Gorospe, M., Davis, R.J., Liu, Y. J. Biol. Chem. (2001) [Pubmed]
  10. Conditional expression of MAP kinase phosphatase-2 protects against genotoxic stress-induced apoptosis by binding and selective dephosphorylation of nuclear activated c-jun N-terminal kinase. Cadalbert, L., Sloss, C.M., Cameron, P., Plevin, R. Cell. Signal. (2005) [Pubmed]
  11. The mitogen-activated protein kinase phosphatases PAC1, MKP-1, and MKP-2 have unique substrate specificities and reduced activity in vivo toward the ERK2 sevenmaker mutation. Chu, Y., Solski, P.A., Khosravi-Far, R., Der, C.J., Kelly, K. J. Biol. Chem. (1996) [Pubmed]
  12. Mechanisms regulating the constitutive activation of the extracellular signal-regulated kinase (ERK) signaling pathway in ovarian cancer and the effect of ribonucleic acid interference for ERK1/2 on cancer cell proliferation. Steinmetz, R., Wagoner, H.A., Zeng, P., Hammond, J.R., Hannon, T.S., Meyers, J.L., Pescovitz, O.H. Mol. Endocrinol. (2004) [Pubmed]
  13. Mitogen-activated protein kinase phosphatases inactivate stress-activated protein kinase pathways in vivo. Hirsch, D.D., Stork, P.J. J. Biol. Chem. (1997) [Pubmed]
  14. Isolation and characterisation of a uniquely regulated threonine, tyrosine phosphatase (TYP 1) which inactivates ERK2 and p54jnk. King, A.G., Ozanne, B.W., Smythe, C., Ashworth, A. Oncogene (1995) [Pubmed]
  15. Mitogen-activated protein kinases in schizophrenia. Kyosseva, S.V., Elbein, A.D., Griffin, W.S., Mrak, R.E., Lyon, M., Karson, C.N. Biol. Psychiatry (1999) [Pubmed]
  16. Effects of a redox-active agent on lymphocyte activation and early gene expression patterns. Hardy, K., Hunt, N.H. Free Radic. Biol. Med. (2004) [Pubmed]
  17. Pancreatic tumor cells with mutant K-ras suppress ERK activity by MEK-dependent induction of MAP kinase phosphatase-2. Yip-Schneider, M.T., Lin, A., Marshall, M.S. Biochem. Biophys. Res. Commun. (2001) [Pubmed]
  18. Inhibition of Gluconeogenesis through Transcriptional Activation of EGR1 and DUSP4 by AMP-activated Kinase. Berasi, S.P., Huard, C., Li, D., Shih, H.H., Sun, Y., Zhong, W., Paulsen, J.E., Brown, E.L., Gimeno, R.E., Martinez, R.V. J. Biol. Chem. (2006) [Pubmed]
  19. Differential gene expression in ovarian tumors reveals Dusp 4 and Serpina 5 as key regulators for benign behavior of serous borderline tumors. Sieben, N.L., Oosting, J., Flanagan, A.M., Prat, J., Roemen, G.M., Kolkman-Uljee, S.M., van Eijk, R., Cornelisse, C.J., Fleuren, G.J., van Engeland, M. J. Clin. Oncol. (2005) [Pubmed]
  20. Inactivation of JNK activity by mitogen-activated protein kinase phosphatase-2 in EAhy926 endothelial cells is dependent upon agonist-specific JNK translocation to the nucleus. Robinson, C.J., Sloss, C.M., Plevin, R. Cell. Signal. (2001) [Pubmed]
  21. Reciprocal modulation of mitogen-activated protein kinases and mitogen-activated protein kinase phosphatase 1 and 2 in failing human myocardium. Communal, C., Colucci, W.S., Remondino, A., Sawyer, D.B., Port, J.D., Wichman, S.E., Bristow, M.R., Singh, K. J. Card. Fail. (2002) [Pubmed]
  22. Detection of primate herpesvirus antibodies including Herpesvirus simiae by enzyme immunoassay. Eichberg, J.W., Heberling, R.L., Guajardo, J.E., Kalter, S.S. Dev. Biol. Stand. (1980) [Pubmed]
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