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Gene Review

Map2k5  -  mitogen-activated protein kinase kinase 5

Mus musculus

Synonyms: AI324775, AI428457, Dual specificity mitogen-activated protein kinase kinase 5, MAP kinase kinase 5, MAPK/ERK kinase 5, ...
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Disease relevance of Map2k5


High impact information on Map2k5

  • Moreover, a dominant-negative MEK5 mutant specifically blocked LIF-induced elongation of cardiomyocytes and reduced expression of fetal cardiac genes without blocking other aspects of LIF-induced hypertrophy [1].
  • The alternative splicing of the mek5 gene gives rise to two isoforms [2].
  • Overall, this is the first study to rigorously establish the role of MEK5 in vivo as an activator of ERK5 and as an essential regulator of cell survival that is required for normal embryonic development [3].
  • The absence of MEK5 does not affect cell cycle progression but sensitizes mouse embryonic fibroblasts (MEFs) to the ability of sorbitol to enhance caspase 3 activity [3].
  • The phenotype of the mek5(-/-) embryos includes abnormal cardiac development as well as a marked decrease in proliferation and an increase in apoptosis in the heart, head, and dorsal regions of the mutant embryos [3].

Biological context of Map2k5


Anatomical context of Map2k5

  • Expression of the constitutively active MEK5 also increased the survival of BAF3 cells cultured in the absence of or in low concentrations of G-CSF [5].

Physical interactions of Map2k5


Enzymatic interactions of Map2k5

  • Activated MEK5 then phosphorylates and activates ERK5 [7].

Regulatory relationships of Map2k5

  • The proliferation of BAF3 cells in response to G-CSF was inhibited by expression of a dominant-negative MEK5 but potentiated by expression of a constitutively active MEK5 [5].

Other interactions of Map2k5

  • Of the two isoforms upstream of MAPK-kinase 5 (MEK5) known to exist, only the longer MEK5alpha isoform potently activates BMK1 [8].

Analytical, diagnostic and therapeutic context of Map2k5


  1. Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy. Nicol, R.L., Frey, N., Pearson, G., Cobb, M., Richardson, J., Olson, E.N. EMBO J. (2001) [Pubmed]
  2. A novel mitogen-activated protein kinase docking site in the N terminus of MEK5alpha organizes the components of the extracellular signal-regulated kinase 5 signaling pathway. Seyfried, J., Wang, X., Kharebava, G., Tournier, C. Mol. Cell. Biol. (2005) [Pubmed]
  3. Targeted deletion of mek5 causes early embryonic death and defects in the extracellular signal-regulated kinase 5/myocyte enhancer factor 2 cell survival pathway. Wang, X., Merritt, A.J., Seyfried, J., Guo, C., Papadakis, E.S., Finegan, K.G., Kayahara, M., Dixon, J., Boot-Handford, R.P., Cartwright, E.J., Mayer, U., Tournier, C. Mol. Cell. Biol. (2005) [Pubmed]
  4. MEF2C regulates c-Jun but not TNF-alpha gene expression in stimulated mast cells. Wei, X., Sun, W., Fan, R., Hahn, J., Joetham, A., Li, G., Webb, S., Garrington, T., Dakhama, A., Lucas, J., Johnson, G.L., Gelfand, E.W. Eur. J. Immunol. (2003) [Pubmed]
  5. Granulocyte colony-stimulating factor induces ERK5 activation, which is differentially regulated by protein-tyrosine kinases and protein kinase C. Regulation of cell proliferation and survival. Dong, F., Gutkind, J.S., Larner, A.C. J. Biol. Chem. (2001) [Pubmed]
  6. Noncanonical function of MEKK2 and MEK5 PB1 domains for coordinated extracellular signal-regulated kinase 5 and c-Jun N-terminal kinase signaling. Nakamura, K., Johnson, G.L. Mol. Cell. Biol. (2007) [Pubmed]
  7. PB1 domains of MEKK2 and MEKK3 interact with the MEK5 PB1 domain for activation of the ERK5 pathway. Nakamura, K., Johnson, G.L. J. Biol. Chem. (2003) [Pubmed]
  8. Activation of big MAP kinase 1 (BMK1/ERK5) inhibits cardiac injury after myocardial ischemia and reperfusion. Cameron, S.J., Itoh, S., Baines, C.P., Zhang, C., Ohta, S., Che, W., Glassman, M., Lee, J.D., Yan, C., Yang, J., Abe, J. FEBS Lett. (2004) [Pubmed]
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