EC - Mitogen-activated protein kinase kinase

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IntEnz Enzyme Nomenclature


Accepted name:
mitogen-activated protein kinase kinase
Other names:
MAP kinase kinase
MAP kinase kinase 4
MAP kinase kinase 7
MAP kinase or ERK kinase
Systematic name:
ATP:protein phosphotransferase (MAPKKK-activated)



This enzyme is a dual-specific protein kinase and requires mitogen-activated protein kinase kinase kinase (MAPKKK) for activation. It is required for activation of EC, mitogen-activated protein kinase. Phosphorylation of MEK1 by Raf involves phosphorylation of two serine residues [5]. Mitogen-activated protein kinase (MAPK) signal transduction pathways are among the most widespread mechanisms of cellular regulation. Mammalian MAPK pathways can be recruited by a wide variety of stimuli including hormones (e.g. insulin and growth hormone), mitogens (e.g. epidermal growth factor and platelet-derived growth factor), vasoactive peptides (e.g. angiotensin-II and endothelin), inflammatory cytokines of the tumour necrosis factor (TNF) family and environmental stresses such as osmotic shock, ionizing radiation and ischaemic injury.

Links to other databases

Enzymes and pathways: NC-IUBMB , BRENDA , ExplorEnz , ENZYME@ExPASy , KEGG , MetaCyc , UniPathway
Protein domains and families: PROSITE:PDOC00100
Structural data: CSA , EC2PDB
Gene Ontology: GO:0004708
UniProtKB/Swiss-Prot: (101) [show] [UniProt]


  1. Mordret, G.
    MAP kinase kinase: a node connecting multiple pathways.
    Biol. Cell 79 : 193-207 (1993). [PMID: 8004006]
  2. Zheng, C.-F. and Guan, K.-L.
    Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2.
    J. Biol. Chem. 268 : 11435-11439 (1993). [PMID: 8388392]
  3. Wu, J., Harrison, J.K., Dent, P., Lynch, K.R., Weber, M.J. and Sturgill, T.W.
    Identification and characterization of a new mammalian mitogen-activated protein kinase kinase, MKK2.
    Mol. Cell. Biol. 13 : 4539-4548 (1993). [PMID: 8393135]
  4. Alessi, D.R., Saito, Y., Campbell, D.G., Cohen, P., Sithanandam, G., Rapp, U., Ashworth, A., Marshall, C.J. and Cowley, S.
    Identification of the sites in MAP kinase kinase-1 phosphorylated by p74raf-1.
    EMBO J. 13 : 1610-1619 (1994). [PMID: 8157000]
  5. Pham, C.D., Arlinghaus, R.B., Zheng, C.F., Guan, K.L. and Singh, B.
    Characterization of MEK1 phosphorylation by the v-Mos protein.
    Oncogene 10 : 1683-1688 (1995). [PMID: 7731726]
  6. Han, J., Lee, J.-D., Jiang, Y., Li, Z., Feng, L. and Ulevitch, R.J.
    Characterization of the structure and function of a novel MAP kinase kinase (MKK6).
    J. Biol. Chem. 271 : 2886-2891 (1996). [PMID: 8621675]

[EC created 2005]