DUSP4 explained

Dual specificity protein phosphatase 4 is an enzyme that in humans is encoded by the DUSP4 gene.^{[1] [2] [3]}

Function

The protein encoded by this gene is a member of the dual specificity protein phosphatase subfamily. These phosphatases inactivate their target kinases by dephosphorylating both the phosphoserine/threonine and phosphotyrosine residues. They negatively regulate members of the mitogen-activated protein (MAP) kinase superfamily (MAPK/ERK, SAPK/JNK, p38), which are associated with cellular proliferation and differentiation. Different members of the family of dual specificity phosphatases show distinct substrate specificities for various MAP kinases, different tissue distribution and subcellular localization, and different modes of inducibility of their expression by extracellular stimuli. This gene product inactivates ERK1, ERK2 and JNK, is expressed in a variety of tissues, and is localized in the nucleus. Two alternatively spliced transcript variants, encoding distinct isoforms, have been observed for this gene. In addition, multiple polyadenylation sites have been reported.^[3]

In melanocytic cells DUSP4 gene expression may be regulated by MITF.^[4]

Further reading

• King AG, Ozanne BW, Smythe C, Ashworth A . Isolation and characterisation of a uniquely regulated threonine, tyrosine phosphatase (TYP 1) which inactivates ERK2 and p54jnk . Oncogene . 11 . 12 . 2553–63 . Dec 1995 . 8545112 .
• Chu Y, Solski PA, Khosravi-Far R, Der CJ, Kelly K . 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 . The Journal of Biological Chemistry . 271 . 11 . 6497–501 . Mar 1996 . 8626452 . 10.1074/jbc.271.11.6497 . free .
• Bonaldo MF, Lennon G, Soares MB . Normalization and subtraction: two approaches to facilitate gene discovery . Genome Research . 6 . 9 . 791–806 . Sep 1996 . 8889548 . 10.1101/gr.6.9.791 . free .
• Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG . Proteomic analysis of NMDA receptor-adhesion protein signaling complexes . Nature Neuroscience . 3 . 7 . 661–9 . Jul 2000 . 10862698 . 10.1038/76615 . 1842/742 . 14392630 . free .
• Chen P, Hutter D, Yang X, Gorospe M, Davis RJ, Liu Y . 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 . The Journal of Biological Chemistry . 276 . 31 . 29440–9 . Aug 2001 . 11387337 . 10.1074/jbc.M103463200 . free .
• Cadalbert L, Sloss CM, Cameron P, Plevin R . 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 . Cellular Signalling . 17 . 10 . 1254–64 . Oct 2005 . 16038800 . 10.1016/j.cellsig.2005.01.003 .
• Huda Zoghbi . Rual JF, Venkatesan K, Hao T, Hirozane-Kishikawa T, Dricot A, Li N, Berriz GF, Gibbons FD, Dreze M, Ayivi-Guedehoussou N, Klitgord N, Simon C, Boxem M, Milstein S, Rosenberg J, Goldberg DS, Zhang LV, Wong SL, Franklin G, Li S, Albala JS, Lim J, Fraughton C, Llamosas E, Cevik S, Bex C, Lamesch P, Sikorski RS, Vandenhaute J, Zoghbi HY, Smolyar A, Bosak S, Sequerra R, Doucette-Stamm L, Cusick ME, Hill DE, Roth FP, Vidal M . Towards a proteome-scale map of the human protein-protein interaction network . Nature . 437 . 7062 . 1173–8 . Oct 2005 . 16189514 . 10.1038/nature04209 . 2005Natur.437.1173R . 4427026 .
• Tresini M, Lorenzini A, Torres C, Cristofalo VJ . Modulation of replicative senescence of diploid human cells by nuclear ERK signaling . The Journal of Biological Chemistry . 282 . 6 . 4136–51 . Feb 2007 . 17145763 . 10.1074/jbc.M604955200 . free .
• Wang J, Shen WH, Jin YJ, Brandt-Rauf PW, Yin Y . A molecular link between E2F-1 and the MAPK cascade . The Journal of Biological Chemistry . 282 . 25 . 18521–31 . Jun 2007 . 17452331 . 10.1074/jbc.M610538200 . free .

Notes and References

1. Guan KL, Butch E . Isolation and characterization of a novel dual specific phosphatase, HVH2, which selectively dephosphorylates the mitogen-activated protein kinase . The Journal of Biological Chemistry . 270 . 13 . 7197–203 . Mar 1995 . 7535768 . 10.1074/jbc.270.13.7197 . free .
2. Smith A, Price C, Cullen M, Muda M, King A, Ozanne B, Arkinstall S, Ashworth A . Chromosomal localization of three human dual specificity phosphatase genes (DUSP4, DUSP6, and DUSP7) . Genomics . 42 . 3 . 524–7 . Jun 1997 . 9205128 . 10.1006/geno.1997.4756 .
3. Web site: Entrez Gene: DUSP4 dual specificity phosphatase 4.
4. Hoek KS, Schlegel NC, Eichhoff OM, Widmer DS, Praetorius C, Einarsson SO, Valgeirsdottir S, Bergsteinsdottir K, Schepsky A, Dummer R, Steingrimsson E . Novel MITF targets identified using a two-step DNA microarray strategy . Pigment Cell & Melanoma Research . 21 . 6 . 665–76 . Dec 2008 . 19067971 . 10.1111/j.1755-148X.2008.00505.x . 24698373 . free .