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Gene Review

MAP2K2  -  mitogen-activated protein kinase kinase 2

Homo sapiens

Synonyms: CFC4, Dual specificity mitogen-activated protein kinase kinase 2, ERK activator kinase 2, MAP kinase kinase 2, MAPK/ERK kinase 2, ...
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Disease relevance of MAP2K2


High impact information on MAP2K2

  • The results indicate that the phosphorylation of these two keratins is independently controlled by cyclic AMP-dependent kinase for MEK-2 and by cyclic nucleotide-independent kinase for MEK-1 [5].
  • V8 protease digests revealed that phosphorylation of MEK-2 is restricted to one peptide representing approximately half the molecule [5].
  • The phosphorylation of MEK-2 increased in the presence of 10(-4) M dibutyryl cyclic AMP (twofold), 1 mM methylisobutylxanthine (2.5-fold), 10(-5) M isoproterenol (fivefold), and 10(-9) M cholera toxin (sevenfold) [5].
  • The ME-180 keratin proteins consist of two major subunits designated MEK-1 and MEK-2 with approximate molecular weights of 58,000 and 53,000, respectively, and six minor subunits of 59, 57, 52.5, 50.5, 45, and 40 kilodaltons [5].
  • In this study, we show that YopJ exerts its deleterious effects by catalyzing the acetylation of two serine residues in the activation loop of the MAP kinase kinase, MEK2 [6].

Biological context of MAP2K2


Anatomical context of MAP2K2

  • Chemotactic peptide-induced activation of MEK-2, the predominant isoform in human neutrophils. Inhibition by wortmannin [11].
  • Like MEK-1, MEK-2 was found to reside in the cytosol both before and after stimulation [11].
  • Selective activation of MEK1 but not MEK2 by A-Raf from epidermal growth factor-stimulated Hela cells [12].
  • Introduction of Ras dominant-negative (D/N) and MEK2 D/N genes into ChangX-34 cells significantly alleviated centrosome amplification, whereas introduction of the PKC D/N and PKB D/N genes did not [13].
  • However, U0126 (a MEK1/2 inhibitor) treatment apparently induced the plasma membrane distribution of claudin-1 and aggregation of single cells in PC-1.0 and AsPC-1 cells, synchronously seriously suppressed MEK2 and p-MEK1/2 expression [14].

Associations of MAP2K2 with chemical compounds

  • MAPKK1 and MAPKK2 have apparent molecular masses of 45 kDa and 47 kDa, respectively, on SDS/polyacrylamide gel electrophoresis [15].
  • 5. In contrast, UO126 was highly effective at inhibiting IL-1beta-dependent arachidonate release, implicating MEK2 in the activation of the PLA(2) that is involved in IL-1beta-dependent PGE(2) release [16].
  • 6. We conclude that the MEK1, MEK2 and p38 MAP kinase inhibitors, PD098059, UO126 and SB203580, are highly potent in respect of inflammatory PG release [16].
  • METHODS: Human ASM cells were cultured in 96-well plates with or without cerivastatin in the presence or absence of mitogen-activated protein (MAP) kinase (MAPK)/extracellular signal-regulated kinase (ERK) kinase MEK1/MEK 2 inhibitor PD98059 [17].
  • When ME-180 cells were incubated for 2-24 h in the presence of [32P]orthophosphate, MEK-1 and MEK-2 as well as the 52.5- and 40-kilodalton keratins were phosphorylated at their serine residues [5].

Enzymatic interactions of MAP2K2


Regulatory relationships of MAP2K2


Other interactions of MAP2K2


Analytical, diagnostic and therapeutic context of MAP2K2


  1. Analysis of invasion-metastasis mechanism in pancreatic cancer: involvement of tight junction transmembrane protein occludin and MEK/ERK signal transduction pathway in cancer cell dissociation. Tan, X., Tamori, Y., Egami, H., Ishikawa, S., Kurizaki, T., Takai, E., Hirota, M., Ogawa, M. Oncol. Rep. (2004) [Pubmed]
  2. Phase I and pharmacodynamic study of the oral MEK inhibitor CI-1040 in patients with advanced malignancies. Lorusso, P.M., Adjei, A.A., Varterasian, M., Gadgeel, S., Reid, J., Mitchell, D.Y., Hanson, L., DeLuca, P., Bruzek, L., Piens, J., Asbury, P., Van Becelaere, K., Herrera, R., Sebolt-Leopold, J., Meyer, M.B. J. Clin. Oncol. (2005) [Pubmed]
  3. Mutation analysis of the coding sequences of MEK-1 and MEK-2 genes in human lung cancer cell lines. Bansal, A., Ramirez, R.D., Minna, J.D. Oncogene (1997) [Pubmed]
  4. Identification of genes related to invasion and metastasis in pancreatic cancer by cDNA representational difference analysis. Ishikawa, S., Egami, H., Kurizaki, T., Akagi, J., Tamori, Y., Yoshida, N., Tan, X., Hayashi, N., Ogawa, M. J. Exp. Clin. Cancer Res. (2003) [Pubmed]
  5. Dual regulation of intermediate filament phosphorylation. Gilmartin, M.E., Mitchell, J., Vidrich, A., Freedberg, I.M. J. Cell Biol. (1984) [Pubmed]
  6. Acetylation of MEK2 and I{kappa}B kinase (IKK) activation loop residues by YopJ inhibits signaling. Mittal, R., Peak-Chew, S.Y., McMahon, H.T. Proc. Natl. Acad. Sci. U.S.A. (2006) [Pubmed]
  7. Chromosome mapping of the human genes encoding the MAP kinase kinase MEK1 (MAP2K1) to 15q21 and MEK2 (MAP2K2) to 7q32. Meloche, S., Gopalbhai, K., Beatty, B.G., Scherer, S.W., Pellerin, J. Cytogenet. Cell Genet. (2000) [Pubmed]
  8. Reduced stability of mitogen-activated protein kinase kinase-2 mRNA and phosphorylation of poly(A)-binding protein (PABP) in cells overexpressing PABP. Ma, S., Musa, T., Bag, J. J. Biol. Chem. (2006) [Pubmed]
  9. PD 098059 is a specific inhibitor of the activation of mitogen-activated protein kinase kinase in vitro and in vivo. Alessi, D.R., Cuenda, A., Cohen, P., Dudley, D.T., Saltiel, A.R. J. Biol. Chem. (1995) [Pubmed]
  10. CI-1040 (PD184352), a targeted signal transduction inhibitor of MEK (MAPKK). Allen, L.F., Sebolt-Leopold, J., Meyer, M.B. Semin. Oncol. (2003) [Pubmed]
  11. Chemotactic peptide-induced activation of MEK-2, the predominant isoform in human neutrophils. Inhibition by wortmannin. Downey, G.P., Butler, J.R., Brumell, J., Borregaard, N., Kjeldsen, L., Sue-A-Quan, A.K., Grinstein, S. J. Biol. Chem. (1996) [Pubmed]
  12. Selective activation of MEK1 but not MEK2 by A-Raf from epidermal growth factor-stimulated Hela cells. Wu, X., Noh, S.J., Zhou, G., Dixon, J.E., Guan, K.L. J. Biol. Chem. (1996) [Pubmed]
  13. Mitotic aberration coupled with centrosome amplification is induced by hepatitis B virus X oncoprotein via the Ras-mitogen-activated protein/extracellular signal-regulated kinase-mitogen-activated protein pathway. Yun, C., Cho, H., Kim, S.J., Lee, J.H., Park, S.Y., Chan, G.K., Cho, H. Mol. Cancer Res. (2004) [Pubmed]
  14. Arrangement of expression and distribution of tight junction protein claudin-1 in cell dissociation of pancreatic cancer cells. Tan, X., Egami, H., Ishikawa, S., Kurizaki, T., Nakagawa, M., Hirota, M., Ogawa, M. Int. J. Oncol. (2004) [Pubmed]
  15. Activation of two isoforms of mitogen-activated protein kinase kinase in response to epidermal growth factor and nerve growth factor. Moriguchi, T., Gotoh, Y., Nishida, E. Eur. J. Biochem. (1995) [Pubmed]
  16. The MAP kinase inhibitors, PD098059, UO126 and SB203580, inhibit IL-1beta-dependent PGE(2) release via mechanistically distinct processes. Newton, R., Cambridge, L., Hart, L.A., Stevens, D.A., Lindsay, M.A., Barnes, P.J. Br. J. Pharmacol. (2000) [Pubmed]
  17. Cerivastatin-induced apoptosis of human aortic smooth muscle cells through partial inhibition of basal activation of extracellular signal-regulated kinases. Takata, R., Fukasawa, S., Hara, T., Nakajima, H., Yamashina, A., Yanase, N., Mizuguchi, J. Cardiovascular pathology : the official journal of the Society for Cardiovascular Pathology. (2004) [Pubmed]
  18. Contributions of the mitogen-activated protein (MAP) kinase backbone and phosphorylation loop to MEK specificity. Robinson, M.J., Cheng, M., Khokhlatchev, A., Ebert, D., Ahn, N., Guan, K.L., Stein, B., Goldsmith, E., Cobb, M.H. J. Biol. Chem. (1996) [Pubmed]
  19. Relationship between activation of epidermal growth factor receptor and cell dissociation in pancreatic cancer. Tan, X., Egami, H., Ishikawa, S., Nakagawa, M., Ishiko, T., Kamohara, H., Hirota, M., Ogawa, M. Int. J. Oncol. (2004) [Pubmed]
  20. Characterization of Raf-1 activation in mitosis. Laird, A.D., Morrison, D.K., Shalloway, D. J. Biol. Chem. (1999) [Pubmed]
  21. Importance of MEK in neutrophil microbicidal responsiveness. Downey, G.P., Butler, J.R., Tapper, H., Fialkow, L., Saltiel, A.R., Rubin, B.B., Grinstein, S. J. Immunol. (1998) [Pubmed]
  22. Docking sites on mitogen-activated protein kinase (MAPK) kinases, MAPK phosphatases and the Elk-1 transcription factor compete for MAPK binding and are crucial for enzymic activity. Bardwell, A.J., Abdollahi, M., Bardwell, L. Biochem. J. (2003) [Pubmed]
  23. Basic fibroblast growth factor induces the expression of matrix metalloproteinase-3 in human periodontal ligament cells through the MEK2 mitogen-activated protein kinase pathway. Shimazu, A., Morishita, M. J. Periodont. Res. (2003) [Pubmed]
  24. Components of a new human protein kinase signal transduction pathway. Zhou, G., Bao, Z.Q., Dixon, J.E. J. Biol. Chem. (1995) [Pubmed]
  25. Phosphorylation regulates nucleophosmin targeting to the centrosome during mitosis as detected by cross-reactive phosphorylation-specific MKK1/MKK2 antibodies. Cha, H., Hancock, C., Dangi, S., Maiguel, D., Carrier, F., Shapiro, P. Biochem. J. (2004) [Pubmed]
  26. Digoxigenin-labeled peptides for the immunological quantification of intracellular signaling proteins: application to the MAP kinase kinase isoform MEK2. Blais, C., Drapeau, G., Meloche, S., Morais, R., Adam, A. BioTechniques (1997) [Pubmed]
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