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 MKP-3 has been shown to alleviate chronic postoperative pain.
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Kim HS, Song MC, Kwak IH, Park TJ, Lim IK (September 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 Chemistry. 278 (39): 37497–510. doi:10.1074/jbc.M211739200. PMID12840032.
Kim Y, Rice AE, Denu JM (December 2003). "Intramolecular dephosphorylation of ERK by MKP3". Biochemistry. 42 (51): 15197–207. doi:10.1021/bi035346b. PMID14690430.
Karlsson M, Mathers J, Dickinson RJ, Mandl M, Keyse SM (October 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 Chemistry. 279 (40): 41882–91. doi:10.1074/jbc.M406720200. PMID15269220.
Kamata H, Honda S, Maeda S, Chang L, Hirata H, Karin M (March 2005). "Reactive oxygen species promote TNFalpha-induced death and sustained JNK activation by inhibiting MAP kinase phosphatases". Cell. 120 (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 Genetics. 50 (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 (August 2005). "Distinct progression pathways involving the dysfunction of DUSP6/MKP-3 in pancreatic intraepithelial neoplasia and intraductal papillary-mucinous neoplasms of the pancreas". Modern Pathology. 18 (8): 1034–42. doi:10.1038/modpathol.3800383. PMID15832194.