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 ERK2, is expressed in a variety of tissues with the highest levels in heart and pancreas and, unlike most other members of this family, is localized in the cytoplasm. Two transcript variants encoding different isoforms have been found for this gene. Upregulation of spinal MKP-3 has been shown to alleviate chronic postoperative pain.
^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)". Genomics42 (3): 524–7. doi:10.1006/geno.1997.4756. PMID9205128.
^Muda M, Theodosiou A, Gillieron C, Smith A, Chabert C, Camps M, Boschert U, Rodrigues N, Davies K, Ashworth A, Arkinstall S (Apr 1998). "The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity". The Journal of Biological Chemistry273 (15): 9323–9. doi:10.1074/jbc.273.15.9323. PMID9535927.
Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". Gene138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID8125298.
Muda M, Boschert U, Dickinson R, Martinou JC, Martinou I, Camps M, Schlegel W, Arkinstall S (Feb 1996). "MKP-3, a novel cytosolic protein-tyrosine phosphatase that exemplifies a new class of mitogen-activated protein kinase phosphatase". The Journal of Biological Chemistry271 (8): 4319–26. doi:10.1074/jbc.271.8.4319. PMID8626780.
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)". Genomics42 (3): 524–7. doi:10.1006/geno.1997.4756. PMID9205128.
Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". Gene200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID9373149.
Muda M, Theodosiou A, Gillieron C, Smith A, Chabert C, Camps M, Boschert U, Rodrigues N, Davies K, Ashworth A, Arkinstall S (Apr 1998). "The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity". The Journal of Biological Chemistry273 (15): 9323–9. doi:10.1074/jbc.273.15.9323. PMID9535927.
Furukawa T, Yatsuoka T, Youssef EM, Abe T, Yokoyama T, Fukushige S, Soeda E, Hoshi M, Hayashi Y, Sunamura M, Kobari M, Horii A (1999). "Genomic analysis of DUSP6, a dual specificity MAP kinase phosphatase, in pancreatic cancer". Cytogenetics and Cell Genetics82 (3-4): 156–9. doi:10.1159/000015091. PMID9858808.
Stewart AE, Dowd S, Keyse SM, McDonald NQ (Feb 1999). "Crystal structure of the MAPK phosphatase Pyst1 catalytic domain and implications for regulated activation". Nature Structural Biology6 (2): 174–81. doi:10.1038/5861. PMID10048930.
Rössig L, Hermann C, Haendeler J, Assmus B, Zeiher AM, Dimmeler S (Jan 2002). "Angiotensin II-induced upregulation of MAP kinase phosphatase-3 mRNA levels mediates endothelial cell apoptosis". Basic Research in Cardiology97 (1): 1–8. doi:10.1007/s395-002-8381-2. PMID11998972.
Kim HS, Song MC, Kwak IH, Park TJ, Lim IK (Sep 2003). "Constitutive induction of p-Erk1/2 accompanied by reduced activities of protein phosphatases 1 and 2A and MKP3 due to reactive oxygen species during cellular senescence". The Journal of Biological Chemistry278 (39): 37497–510. doi:10.1074/jbc.M211739200. PMID12840032.
Karlsson M, Mathers J, Dickinson RJ, Mandl M, Keyse SM (Oct 2004). "Both nuclear-cytoplasmic shuttling of the dual specificity phosphatase MKP-3 and its ability to anchor MAP kinase in the cytoplasm are mediated by a conserved nuclear export signal". The Journal of Biological Chemistry279 (40): 41882–91. doi:10.1074/jbc.M406720200. PMID15269220.
Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M (Mar 2005). "Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases". Cell120 (5): 649–61. doi:10.1016/j.cell.2004.12.041. PMID15766528.
Xu S, Furukawa T, Kanai N, Sunamura M, Horii A (2005). "Abrogation of DUSP6 by hypermethylation in human pancreatic cancer". Journal of Human Genetics50 (4): 159–67. doi:10.1007/s10038-005-0235-y. PMID15824892.
Furukawa T, Fujisaki R, Yoshida Y, Kanai N, Sunamura M, Abe T, Takeda K, Matsuno S, Horii A (Aug 2005). "Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas". Modern Pathology18 (8): 1034–42. doi:10.1038/modpathol.3800383. PMID15832194.