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Gene Review

Map2k2  -  mitogen-activated protein kinase kinase 2

Mus musculus

Synonyms: AA589381, Dual specificity mitogen-activated protein kinase kinase 2, ERK activator kinase 2, MAP kinase kinase 2, MAP kinase/Erk kinase, ...
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Disease relevance of Map2k2

  • These results indicate that MK2 plays a key role in regulation of smalpha expression, and that targeting MK2 might present a therapeutic approach in managing conditions such as pulmonary fibrosis [1].
  • Our data propose a role for MK2 in AD brain pathology, for which neuroinflammation involving cytokines and chemokines and overt neuronal loss have been documented [2].
  • In summary, these data show that gene deletion of MK2 ameliorates cerulein-induced pancreatitis [3].
  • We investigated the possible negative regulation of the cell cycle by protein kinase C (PKC) isoforms in synchronously grown BALB/MK-2 mouse keratinocytes, in which PKC isoforms were overexpressed by using the adenovirus vector Ax [4].

High impact information on Map2k2

  • However, despite the sustained loss of full-length mitogen-activated protein kinase kinase 2, by 48 h, TIR macrophages regained diphosphorylated extracellular response kinases 1,2, suggesting an adaptation led to recovery of this signaling pathway [5].
  • Altogether, our findings demonstrate that MEK2 is not necessary for the normal development of the embryo and T-cell lineages, suggesting that the loss of MEK2 can be compensated for by MEK1 [6].
  • Mek2 is dispensable for mouse growth and development [6].
  • Although several components of the ERK/MAP kinase cascade have been implicated in thymocyte development, no such involvement was observed for MEK2, which appears to be nonessential for thymocyte differentiation and T-cell-receptor-induced proliferation and apoptosis [6].
  • In detached cells placed in suspension, ERK2 was complexed with MEK2 but not with MEK1 [7].

Biological context of Map2k2


Anatomical context of Map2k2


Associations of Map2k2 with chemical compounds

  • Recombinant MEK2 produced in bacteria phosphorylates a kinase-inactive Erk-1 on tyrosine and threonine, whereas a kinase-inactive mutant MEK2 does not [8].
  • Using a murine knockout model, we have previously shown that elimination of MK2 leads to a dramatic reduction of tumor necrosis factor (TNF) production in response to lipopolysaccharide [10].
  • In addition, a specific MEK1/MEK2 inhibitor, PD98059 (60 microM), reduced the GnRH and PMA responses whereas the L-type voltage-gated calcium channel agonist, +/- BayK 8644 (5 microM), and antagonist, nimodipine (250 nM), had no effect on GnRH responsiveness [14].
  • Neurite outgrowth, increased expression of growth-associated protein 43, and decreased incorporation of bromodeoxyuridine (BrdU) were induced by treatment with GDNF, H-RasV12, or a constitutively active MEK2 [15].
  • Surprisingly, MEK2 but not MEK1 was the principal mediator of estradiol-induced activation of ERK [16].

Physical interactions of Map2k2

  • We show that MK2 stabilizes p38 MAPK through its C terminus and that MK2 catalytic activity does not contribute to this stabilization [10].

Regulatory relationships of Map2k2


Other interactions of Map2k2


Analytical, diagnostic and therapeutic context of Map2k2


  1. Smooth muscle alpha-actin expression and myofibroblast differentiation by TGFbeta are dependent upon MK2. Sousa, A.M., Liu, T., Guevara, O., Stevens, J., Fanburg, B.L., Gaestel, M., Toksoz, D., Kayyali, U.S. J. Cell. Biochem. (2007) [Pubmed]
  2. MAPK-activated protein kinase 2 deficiency in microglia inhibits pro-inflammatory mediator release and resultant neurotoxicity. Relevance to neuroinflammation in a transgenic mouse model of Alzheimer disease. Culbert, A.A., Skaper, S.D., Howlett, D.R., Evans, N.A., Facci, L., Soden, P.E., Seymour, Z.M., Guillot, F., Gaestel, M., Richardson, J.C. J. Biol. Chem. (2006) [Pubmed]
  3. Gene deletion of MK2 inhibits TNF-alpha and IL-6 and protects against cerulein-induced pancreatitis. Tietz, A.B., Malo, A., Diebold, J., Kotlyarov, A., Herbst, A., Kolligs, F.T., Brandt-Nedelev, B., Halangk, W., Gaestel, M., Göke, B., Schäfer, C. Am. J. Physiol. Gastrointest. Liver Physiol. (2006) [Pubmed]
  4. Phorbol ester-induced G1 arrest in BALB/MK-2 mouse keratinocytes is mediated by delta and eta isoforms of protein kinase C. Ishino, K., Ohba, M., Kashiwagi, M., Kawabe, S., Chida, K., Kuroki, T. Jpn. J. Cancer Res. (1998) [Pubmed]
  5. Toxin-induced resistance in Bacillus anthracis lethal toxin-treated macrophages. Salles, I.I., Tucker, A.E., Voth, D.E., Ballard, J.D. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  6. Mek2 is dispensable for mouse growth and development. Bélanger, L.F., Roy, S., Tremblay, M., Brott, B., Steff, A.M., Mourad, W., Hugo, P., Erikson, R., Charron, J. Mol. Cell. Biol. (2003) [Pubmed]
  7. Rac-PAK signaling stimulates extracellular signal-regulated kinase (ERK) activation by regulating formation of MEK1-ERK complexes. Eblen, S.T., Slack, J.K., Weber, M.J., Catling, A.D. Mol. Cell. Biol. (2002) [Pubmed]
  8. MEK2 is a kinase related to MEK1 and is differentially expressed in murine tissues. Brott, B.K., Alessandrini, A., Largaespada, D.A., Copeland, N.G., Jenkins, N.A., Crews, C.M., Erikson, R.L. Cell Growth Differ. (1993) [Pubmed]
  9. Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2. Zheng, C.F., Guan, K.L. J. Biol. Chem. (1993) [Pubmed]
  10. Distinct cellular functions of MK2. Kotlyarov, A., Yannoni, Y., Fritz, S., Laass, K., Telliez, J.B., Pitman, D., Lin, L.L., Gaestel, M. Mol. Cell. Biol. (2002) [Pubmed]
  11. Preferential involvement of MEK1 in the tumor necrosis factor-alpha-induced activation of p42mapk/erk2 in mouse macrophages. Winston, B.W., Remigio, L.K., Riches, D.W. J. Biol. Chem. (1995) [Pubmed]
  12. Mitogen-activated protein kinase dynamics during the meiotic G2/MI transition of mouse spermatocytes. Inselman, A., Handel, M.A. Biol. Reprod. (2004) [Pubmed]
  13. Embryonic death of Mek1-deficient mice reveals a role for this kinase in angiogenesis in the labyrinthine region of the placenta. Giroux, S., Tremblay, M., Bernard, D., Cardin-Girard, J.F., Aubry, S., Larouche, L., Rousseau, S., Huot, J., Landry, J., Jeannotte, L., Charron, J. Curr. Biol. (1999) [Pubmed]
  14. Homologous regulation of the gonadotropin-releasing hormone receptor gene is partially mediated by protein kinase C activation of an activator protein-1 element. White, B.R., Duval, D.L., Mulvaney, J.M., Roberson, M.S., Clay, C.M. Mol. Endocrinol. (1999) [Pubmed]
  15. GDNF-induced leukemia inhibitory factor can mediate differentiation via the MEK/ERK pathway in pheochromocytoma cells derived from nf1-heterozygous knockout mice. Park, J.I., Powers, J.F., Tischler, A.S., Strock, C.J., Ball, D.W., Nelkin, B.D. Exp. Cell Res. (2005) [Pubmed]
  16. Estradiol-induced phosphorylation of ERK1/2 in explants of the mouse cerebral cortex: the roles of heat shock protein 90 (Hsp90) and MEK2. Sétáló, G., Singh, M., Guan, X., Toran-Allerand, C.D. J. Neurobiol. (2002) [Pubmed]
  17. Abnormal migration phenotype of mitogen-activated protein kinase-activated protein kinase 2-/- neutrophils in Zigmond chambers containing formyl-methionyl-leucyl-phenylalanine gradients. Hannigan, M.O., Zhan, L., Ai, Y., Kotlyarov, A., Gaestel, M., Huang, C.K. J. Immunol. (2001) [Pubmed]
  18. Regulation of Mouse Inducible Costimulator (ICOS) Expression by Fyn-NFATc2 and ERK Signaling in T Cells. Tan, A.H., Wong, S.C., Lam, K.P. J. Biol. Chem. (2006) [Pubmed]
  19. Nerve growth factor regulates TNF-alpha production in mouse macrophages via MAP kinase activation. Barouch, R., Kazimirsky, G., Appel, E., Brodie, C. J. Leukoc. Biol. (2001) [Pubmed]
  20. Differential expression of MEK1 and MEK2 during mouse development. Alessandrini, A., Brott, B.K., Erikson, R.L. Cell Growth Differ. (1997) [Pubmed]
  21. Airway recruitment of leukocytes in mice is dependent on alpha4-integrins and vascular cell adhesion molecule-1. Chin, J.E., Hatfield, C.A., Winterrowd, G.E., Brashler, J.R., Vonderfecht, S.L., Fidler, S.F., Griffin, R.L., Kolbasa, K.P., Krzesicki, R.F., Sly, L.M., Staite, N.D., Richards, I.M. Am. J. Physiol. (1997) [Pubmed]
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