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Gene Review

Dusp1  -  dual specificity phosphatase 1

Rattus norvegicus

Synonyms: 3CH134, CL100, Cl100, Dual specificity protein phosphatase 1, MAP kinase phosphatase 1, ...
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Disease relevance of Dusp1


Psychiatry related information on Dusp1

  • In PHT gastric mucosa, MKP-1 mRNA and protein expression were increased at baseline versus SO rats and were increased further following alcohol injury with values higher by 20%-40% at each study time versus SO rats [6].
  • MKP-1 induced in rat brain after electroconvulsive shock is independent of regulation of 42- and 44-kDa MAPK activity [7].

High impact information on Dusp1


Chemical compound and disease context of Dusp1

  • Cobalt and deferoxamine also increased MKP-1 mRNA levels, suggesting that hypoxia-inducible factor proteins may play a role in the regulation of MKP-1 by hypoxia [4].
  • We now show that prolonged treatment of VSMCs with 100 nM insulin and high glucose (25 mM) for 12-24 h, to mimic hyperinsulinemia and hyperglycemia, completely blocked MKP-1 mRNA and protein expression in response to subsequent acute insulin treatment [10].

Biological context of Dusp1


Anatomical context of Dusp1


Associations of Dusp1 with chemical compounds

  • TG selectively induced a sustained increase in MAPK phosphatase-1 (MKP-1) mRNA and protein, and these effects were decreased by 2-APB, but not by nimodipine [16].
  • Inhibition of MKP-1 by a protein tyrosine phosphatase inhibitor (vanadate) enhanced H(2)O(2)-triggered apoptosis [11].
  • Selective inhibitors of individual MAP kinases or a dominant-negative mutant of c-jun significantly suppressed the expression of MKP-1 by H(2)O(2) [11].
  • In this study, we investigated the mechanisms through which norepinephrine (NE) regulates MAPK phosphatase-1 (MKP-1) expression in rat pinealocytes [17].
  • At the postreceptor level, treatment with dibutyryl cAMP caused parallel increases in MKP-1 mRNA and protein [17].

Physical interactions of Dusp1

  • Site-directed mutagenesis of the reporter construct combined with band-shift and in vivo studies revealed that part of the constitutive activity of the MKP-1 promoter resides in two GC boxes bound by Sp1 and Sp3 transcription factors in the minimal promoter [18].

Enzymatic interactions of Dusp1


Regulatory relationships of Dusp1

  • Overexpression of wild-type MKP-1 inhibited the phosphorylation of JNK and p38 in cardiomyocytes [20].
  • Both actinomycin D and MKP-1 antisense oligonucleotides inhibited MKP-1 mRNA expression and caused prolonged activation of the p42 and p44 MAP kinases as measured by in-gel-kinase assays and Western blot [21].
  • Vascular smooth muscle cells from spontaneous hypertensive rats exhibited a marked decrease in MKP-1 induction due to defects in insulin-induced iNOS expression because of reductions in PI3-kinase activity [22].
  • MAPK kinase inhibitor PD 98059 did abolish AA-stimulated activation of extracellular signal-regulated kinases but not MKP-1 induction [23].
  • In addition, in CCL39 cells expressing an estradiol-inducible deltaRaf-1::ER chimera, activation of Raf alone is sufficient to induce MKP-1 and MKP-2 [24].

Other interactions of Dusp1

  • These data elucidate, for the first time, that induction of MKP-1 by H(2)O(2) is mediated by the MAP kinase-AP-1 pathway and that the induced MKP-1 is involved in cellular defense against oxidative stress-induced apoptosis of mesangial cells [11].
  • Immunofluorescent image analysis demonstrated trapping of phospho-p38 MAPK in the cytoplasm by MKP-1/CS/green fluorescent protein [25].
  • ET-1-stimulated expression of COX-2 was increased in MKP-1/CS versus LacZ or green fluorescent protein-infected control cells [25].
  • 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 [26].
  • Insulin-mediated MKP-1 expression was preceded by inducible NOS (iNOS) induction and cGMP production [22].

Analytical, diagnostic and therapeutic context of Dusp1


  1. Oxidative stress-inducible protein tyrosine phosphatase in glomerulonephritis. Feng, L., Xia, Y., Seiffert, D., Wilson, C.B. Kidney Int. (1995) [Pubmed]
  2. Osmotic regulation of the heat shock response in H4IIE rat hepatoma cells. Schliess, F., Wiese, S., Haussinger, D. FASEB J. (1999) [Pubmed]
  3. Defective mitogen-activated protein kinase (ERK2) signaling in gastric mucosa of portal hypertensive rats: potential therapeutic implications. Kawanaka, H., Tomikawa, M., Jones, M.K., Szabo, I.L., Pai, R., Baatar, D., Tsugawa, K., Sugimachi, K., Sarfeh, I.J., Tarnawski, A.S. Hepatology (2001) [Pubmed]
  4. Hypoxia-induced regulation of MAPK phosphatase-1 as identified by subtractive suppression hybridization and cDNA microarray analysis. Seta, K.A., Kim, R., Kim, H.W., Millhorn, D.E., Beitner-Johnson, D. J. Biol. Chem. (2001) [Pubmed]
  5. Induction of mitogen-activated protein kinase phosphatase-1 during acute hypertension. Xu, Q., Fawcett, T.W., Gorospe, M., Guyton, K.Z., Liu, Y., Holbrook, N.J. Hypertension (1997) [Pubmed]
  6. Portal hypertensive gastric mucosa has reduced activation of MAP kinase (ERK2) in response to alcohol injury: a key to impaired healing? Kawanaka, H., Tomikawa, M., Jones, M.K., Pai, R., Szabo, I.L., Sugimachi, K., Sarfeh, I.J., Tarnawski, A.S. FASEB J. (2001) [Pubmed]
  7. MKP-1 induced in rat brain after electroconvulsive shock is independent of regulation of 42- and 44-kDa MAPK activity. Jeon, S.H., Yoo, B.H., Kang, U.K., Ahn, Y.M., Bae, C.D., Park, J.B., Kim, Y.S. Biochem. Biophys. Res. Commun. (1998) [Pubmed]
  8. Characterization of gene expression in resting and activated mast cells. Chen, H., Centola, M., Altschul, S.F., Metzger, H. J. Exp. Med. (1998) [Pubmed]
  9. Mitogen-activated protein kinase phosphatase-1 in rat arterial smooth muscle cell proliferation. Lai, K., Wang, H., Lee, W.S., Jain, M.K., Lee, M.E., Haber, E. J. Clin. Invest. (1996) [Pubmed]
  10. High glucose and insulin inhibit VSMC MKP-1 expression by blocking iNOS via p38 MAPK activation. Begum, N., Ragolia, L. Am. J. Physiol., Cell Physiol. (2000) [Pubmed]
  11. Cellular defense against H2O2-induced apoptosis via MAP kinase-MKP-1 pathway. Xu, Q., Konta, T., Nakayama, K., Furusu, A., Moreno-Manzano, V., Lucio-Cazana, J., Ishikawa, Y., Fine, L.G., Yao, J., Kitamura, M. Free Radic. Biol. Med. (2004) [Pubmed]
  12. Molecular genetic responses to lysergic acid diethylamide include transcriptional activation of MAP kinase phosphatase-1, C/EBP-beta and ILAD-1, a novel gene with homology to arrestins. Nichols, C.D., Sanders-Bush, E. J. Neurochem. (2004) [Pubmed]
  13. Biochemical and biological characterization of a neuroendocrine-associated phosphatase. Wang, J.Y., Lin, C.H., Yang, C.H., Tan, T.H., Chen, Y.R. J. Neurochem. (2006) [Pubmed]
  14. Enhanced cortical and accumbal molecular reactivity associated with conditioned heroin, but not sucrose-seeking behaviour. Koya, E., Spijker, S., Voorn, P., Binnekade, R., Schmidt, E.D., Schoffelmeer, A.N., De Vries, T.J., Smit, A.B. J. Neurochem. (2006) [Pubmed]
  15. Mitogen-activated protein kinase phosphatase-1 (MKP-1): >100-fold nocturnal and norepinephrine-induced changes in the rat pineal gland. Price, D.M., Chik, C.L., Terriff, D., Weller, J., Humphries, A., Carter, D.A., Klein, D.C., Ho, A.K. FEBS Lett. (2004) [Pubmed]
  16. Ca2+ source-dependent transcription of CRE-containing genes in vascular smooth muscle. Pulver-Kaste, R.A., Barlow, C.A., Bond, J., Watson, A., Penar, P.L., Tranmer, B., Lounsbury, K.M. Am. J. Physiol. Heart Circ. Physiol. (2006) [Pubmed]
  17. Norepinephrine induction of mitogen-activated protein kinase phosphatase-1 expression in rat pinealocytes: distinct roles of alpha- and beta-adrenergic receptors. Price, D.M., Chik, C.L., Ho, A.K. Endocrinology (2004) [Pubmed]
  18. Stimulated initiation of mitogen-activated protein kinase phosphatase-1 (MKP-1) gene transcription involves the synergistic action of multiple cis-acting elements in the proximal promoter. Ryser, S., Massiha, A., Piuz, I., Schlegel, W. Biochem. J. (2004) [Pubmed]
  19. Abnormal PTEN expression in portal hypertensive gastric mucosa: a key to impaired PI 3-kinase/Akt activation and delayed injury healing? Tsugawa, K., Jones, M.K., Akahoshi, T., Moon, W.S., Maehara, Y., Hashizume, M., Sarfeh, I.J., Tarnawski, A.S. FASEB J. (2003) [Pubmed]
  20. 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]
  21. Mitogen-activated protein (MAP) kinase is regulated by the MAP kinase phosphatase (MKP-1) in vascular smooth muscle cells. Effect of actinomycin D and antisense oligonucleotides. Duff, J.L., Monia, B.P., Berk, B.C. J. Biol. Chem. (1995) [Pubmed]
  22. Regulation of mitogen-activated protein kinase phosphatase-1 induction by insulin in vascular smooth muscle cells. Evaluation of the role of the nitric oxide signaling pathway and potential defects in hypertension. Begum, N., Ragolia, L., Rienzie, J., McCarthy, M., Duddy, N. J. Biol. Chem. (1998) [Pubmed]
  23. Induction of mitogen-activated protein kinase phosphatase-1 by arachidonic acid in vascular smooth muscle cells. Metzler, B., Hu, Y., Sturm, G., Wick, G., Xu, Q. J. Biol. Chem. (1998) [Pubmed]
  24. 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]
  25. Alterations in subcellular localization of p38 MAPK potentiates endothelin-stimulated COX-2 expression in glomerular mesangial cells. Pratt, P.F., Bokemeyer, D., Foschi, M., Sorokin, A., Dunn, M.J. J. Biol. Chem. (2003) [Pubmed]
  26. 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]
  27. Angiotensin II induces 3CH134, a protein-tyrosine phosphatase, in vascular smooth muscle cells. Duff, J.L., Marrero, M.B., Paxton, W.G., Charles, C.H., Lau, L.F., Bernstein, K.E., Berk, B.C. J. Biol. Chem. (1993) [Pubmed]
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