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Mitogen-activated protein kinase kinase 3
Symbols MAP2K3; MAPKK3; MEK3; MKK3; PRKMK3
External IDs OMIM602315 MGI1346868 HomoloGene56430 GeneCards: MAP2K3 Gene
Species Human Mouse
Entrez 5606 26397
Ensembl n/a ENSMUSG00000018932
UniProt n/a Q3TJG7
RefSeq (mRNA) XM_001130488 NM_008928
RefSeq (protein) XP_001130488 NP_032954
Location (UCSC) n/a Chr 11:
60.75 - 60.77 Mb
PubMed search [1] [2]

Dual specificity mitogen-activated protein kinase kinase 3 is an enzyme that in humans is encoded by the MAP2K3 gene.[1]

The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase is activated by mitogenic and environmental stress, and participates in the MAP kinase-mediated signaling cascade. It phosphorylates and thus activates MAPK14/p38-MAPK. This kinase can be activated by insulin, and is necessary for the expression of glucose transporter. Expression of RAS oncogene is found to result in the accumulation of the active form of this kinase, which thus leads to the constitutive activation of MAPK14, and confers oncogenic transformation of primary cells. The inhibition of this kinase is involved in the pathogenesis of Yersina pseudotuberculosis. Multiple alternatively spliced transcript variants that encode distinct isoforms have been reported for this gene.[2]


MAP2K3 has been shown to interact with TAOK2[3] and PLCB2.[4]


  1. ^ Rampoldi L, Zimbello R, Bortoluzzi S, Tiso N, Valle G, Lanfranchi G, Danieli GA (Mar 1998). "Chromosomal localization of four MAPK signaling cascade genes: MEK1, MEK3, MEK4 and MEKK5". Cytogenet Cell Genet 78 (3-4): 301–3. PMID 9465908.  
  2. ^ "Entrez Gene: MAP2K3 mitogen-activated protein kinase kinase 3".  
  3. ^ Chen, Z; Cobb M H (May. 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. (United States) 276 (19): 16070–5. doi:10.1074/jbc.M100681200. ISSN 0021-9258. PMID 11279118.  
  4. ^ Barr, Alastair J; Marjoram Robin, Xu Jing, Snyderman Ralph (Apr. 2002). "Phospholipase C-beta 2 interacts with mitogen-activated protein kinase kinase 3". Biochem. Biophys. Res. Commun. (United States) 293 (1): 647–52. doi:10.1016/S0006-291X(02)00259-0. ISSN 0006-291X. PMID 12054652.  

Further reading

  • Ben-Levy R, Hooper S, Wilson R, et al. (1999). "Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2.". Curr. Biol. 8 (19): 1049–57. doi:10.1016/S0960-9822(98)70442-7. PMID 9768359.  
  • Doza YN, Cuenda A, Thomas GM, et al. (1995). "Activation of the MAP kinase homologue RK requires the phosphorylation of Thr-180 and Tyr-182 and both residues are phosphorylated in chemically stressed KB cells.". FEBS Lett. 364 (2): 223–8. doi:10.1016/0014-5793(95)00346-B. PMID 7750576.  
  • Dérijard B, Raingeaud J, Barrett T, et al. (1995). "Independent human MAP-kinase signal transduction pathways defined by MEK and MKK isoforms.". Science 267 (5198): 682–5. doi:10.1126/science.7839144. PMID 7839144.  
  • Maruyama K, Sugano S (1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides.". Gene 138 (1-2): 171–4. doi:10.1016/0378-1119(94)90802-8. PMID 8125298.  
  • Zheng CF, Guan KL (1993). "Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases.". J. Biol. Chem. 268 (32): 23933–9. PMID 8226933.  
  • Raingeaud J, Whitmarsh AJ, Barrett T, et al. (1996). "MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway.". Mol. Cell. Biol. 16 (3): 1247–55. PMID 8622669.  
  • Stein B, Brady H, Yang MX, et al. (1996). "Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade.". J. Biol. Chem. 271 (19): 11427–33. doi:10.1074/jbc.271.19.11427. PMID 8626699.  
  • Moriguchi T, Toyoshima F, Gotoh Y, et al. (1996). "Purification and identification of a major activator for p38 from osmotically shocked cells. Activation of mitogen-activated protein kinase kinase 6 by osmotic shock, tumor necrosis factor-alpha, and H2O2.". J. Biol. Chem. 271 (43): 26981–8. doi:10.1074/jbc.271.43.26981. PMID 8900184.  
  • Han J, Wang X, Jiang Y, et al. (1997). "Identification and characterization of a predominant isoform of human MKK3.". FEBS Lett. 403 (1): 19–22. doi:10.1016/S0014-5793(97)00021-5. PMID 9038352.  
  • Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, et al. (1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library.". Gene 200 (1-2): 149–56. doi:10.1016/S0378-1119(97)00411-3. PMID 9373149.  
  • Hutchison M, Berman KS, Cobb MH (1998). "Isolation of TAO1, a protein kinase that activates MEKs in stress-activated protein kinase cascades.". J. Biol. Chem. 273 (44): 28625–32. doi:10.1074/jbc.273.44.28625. PMID 9786855.  
  • Chan-Hui PY, Weaver R (1999). "Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase cascades.". Biochem. J. 336 ( Pt 3): 599–609. PMID 9841871.  
  • Chen Z, Hutchison M, Cobb MH (1999). "Isolation of the protein kinase TAO2 and identification of its mitogen-activated protein kinase/extracellular signal-regulated kinase kinase binding domain.". J. Biol. Chem. 274 (40): 28803–7. doi:10.1074/jbc.274.40.28803. PMID 10497253.  
  • Kurata S (2000). "Selective activation of p38 MAPK cascade and mitotic arrest caused by low level oxidative stress.". J. Biol. Chem. 275 (31): 23413–6. doi:10.1074/jbc.C000308200. PMID 10856288.  
  • Majka M, Ratajczak J, Kowalska MA, Ratajczak MZ (2000). "Binding of stromal derived factor-1alpha (SDF-1alpha) to CXCR4 chemokine receptor in normal human megakaryoblasts but not in platelets induces phosphorylation of mitogen-activated protein kinase p42/44 (MAPK), ELK-1 transcription factor and serine/threonine kinase AKT.". Eur. J. Haematol. 64 (3): 164–72. PMID 10997882.  
  • Fleming Y, Armstrong CG, Morrice N, et al. (2001). "Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7.". Biochem. J. 352 Pt 1: 145–54. PMID 11062067.  
  • Venter JC, Adams MD, Myers EW, et al. (2001). "The sequence of the human genome.". Science 291 (5507): 1304–51. doi:10.1126/science.1058040. PMID 11181995.  
  • Chen Z, Cobb MH (2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2.". J. Biol. Chem. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118.  


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