Reaction: ATP + a protein = ADP + a phosphoprotein
Other name(s): MAP kinase kinase; MAP kinase kinase 4; MAP kinase kinase 7; MAP kinase or ERK kinase; MAP2K; MAPKK; MAPKK1; MEK; MEK1; MEK2; MKK; MKK2; MKK4; MKK6; MKK7; STK27
Systematic name: ATP:protein phosphotransferase (MAPKKK-activated)
Comments: 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 2.7.11.24, 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: BRENDA, EXPASY, KEGG, Metacyc, PDB, CAS registry number:
References:
1. Mordret, G. MAP kinase kinase: a node connecting multiple pathways. Biol. Cell. 79 (1993) 193-207. [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 (1993) 11435-11439. [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 (1993) 4539-4548. [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 (1994) 1610-1619. [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 (1995) 1683-1688. [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 (1996) 2886-2891. [PMID: 8621675]