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.
In melanocytic cells DUSP4 gene expression may be regulated by MITF.
^Guan KL, Butch E (Mar 1995). "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. doi:10.1074/jbc.270.13.7197. PMID7535768.
^Smith A, Price C, Cullen M, Muda M, King A, Ozanne B, Arkinstall S, Ashworth A (Jun 1997). "Chromosomal localization of three human dual specificity phosphatase genes (DUSP4, DUSP6, and DUSP7)". Genomics. 42 (3): 524–7. doi:10.1006/geno.1997.4756. PMID9205128.
King AG, Ozanne BW, Smythe C, Ashworth A (Dec 1995). "Isolation and characterisation of a uniquely regulated threonine, tyrosine phosphatase (TYP 1) which inactivates ERK2 and p54jnk". Oncogene. 11 (12): 2553–63. PMID8545112.
Chu Y, Solski PA, Khosravi-Far R, Der CJ, Kelly K (Mar 1996). "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. doi:10.1074/jbc.271.11.6497. PMID8626452.
Bonaldo MF, Lennon G, Soares MB (Sep 1996). "Normalization and subtraction: two approaches to facilitate gene discovery". Genome Research. 6 (9): 791–806. doi:10.1101/gr.6.9.791. PMID8889548.
Husi H, Ward MA, Choudhary JS, Blackstock WP, Grant SG (Jul 2000). "Proteomic analysis of NMDA receptor-adhesion protein signaling complexes". Nature Neuroscience. 3 (7): 661–9. doi:10.1038/76615. PMID10862698.
Chen P, Hutter D, Yang X, Gorospe M, Davis RJ, Liu Y (Aug 2001). "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. doi:10.1074/jbc.M103463200. PMID11387337.
Cadalbert L, Sloss CM, Cameron P, Plevin R (Oct 2005). "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. doi:10.1016/j.cellsig.2005.01.003. PMID16038800.
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 (Oct 2005). "Towards a proteome-scale map of the human protein-protein interaction network". Nature. 437 (7062): 1173–8. doi:10.1038/nature04209. PMID16189514.
Tresini M, Lorenzini A, Torres C, Cristofalo VJ (Feb 2007). "Modulation of replicative senescence of diploid human cells by nuclear ERK signaling". The Journal of Biological Chemistry. 282 (6): 4136–51. doi:10.1074/jbc.M604955200. PMID17145763.
Wang J, Shen WH, Jin YJ, Brandt-Rauf PW, Yin Y (Jun 2007). "A molecular link between E2F-1 and the MAPK cascade". The Journal of Biological Chemistry. 282 (25): 18521–31. doi:10.1074/jbc.M610538200. PMID17452331.