Dual specificity mitogen-activated protein kinase kinase 5 is an enzyme that in humans is encoded by the MAP2K5gene.
The protein encoded by this gene is a dual specificity protein kinase that belongs to the MAP kinase kinase family. This kinase specifically interacts with and activates MAPK7/ERK5. This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs). The signal cascade mediated by this kinase is involved in growth factor stimulated cell proliferation and muscle cell differentiation. Four alternatively spliced transcript variants of this gene encoding distinct isoforms have been described.
^ abSun, W; Kesavan K; Schaefer B C; Garrington T P; Ware M; Johnson N L; Gelfand E W; Johnson G L (Feb 2001). "MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway". J. Biol. Chem. (United States) 276 (7): 5093–100. doi:10.1074/jbc.M003719200. ISSN0021-9258. PMID11073940.
English JM, Vanderbilt CA, Xu S, et al. (1996). "Isolation of MEK5 and differential expression of alternatively spliced forms". J. Biol. Chem.270 (48): 28897–902. doi:10.1074/jbc.270.48.28897. PMID7499418.
Kato Y, Tapping RI, Huang S, et al. (1998). "Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor". Nature395 (6703): 713–6. doi:10.1038/27234. PMID9790194.
English JM, Pearson G, Hockenberry T, et al. (1999). "Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control". J. Biol. Chem.274 (44): 31588–92. doi:10.1074/jbc.274.44.31588. PMID10531364.
Chao TH, Hayashi M, Tapping RI, et al. (2000). "MEKK3 directly regulates MEK5 activity as part of the big mitogen-activated protein kinase 1 (BMK1) signaling pathway". J. Biol. Chem.274 (51): 36035–8. doi:10.1074/jbc.274.51.36035. PMID10593883.
Sun W, Kesavan K, Schaefer BC, et al. (2001). "MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway". J. Biol. Chem.276 (7): 5093–100. doi:10.1074/jbc.M003719200. PMID11073940.
Weldon CB, Scandurro AB, Rolfe KW, et al. (2002). "Identification of mitogen-activated protein kinase kinase as a chemoresistant pathway in MCF-7 cells by using gene expression microarray". Surgery132 (2): 293–301. doi:10.1067/msy.2002.125389. PMID12219026.
Lamark T, Perander M, Outzen H, et al. (2003). "Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins". J. Biol. Chem.278 (36): 34568–81. doi:10.1074/jbc.M303221200. PMID12813044.
Cameron SJ, Abe J, Malik S, et al. (2004). "Differential role of MEK5alpha and MEK5beta in BMK1/ERK5 activation". J. Biol. Chem.279 (2): 1506–12. doi:10.1074/jbc.M308755200. PMID14583600.
Ota T, Suzuki Y, Nishikawa T, et al. (2004). "Complete sequencing and characterization of 21,243 full-length human cDNAs". Nat. Genet.36 (1): 40–5. doi:10.1038/ng1285. PMID14702039.
Bouwmeester T, Bauch A, Ruffner H, et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol.6 (2): 97–105. doi:10.1038/ncb1086. PMID14743216.
Raviv Z, Kalie E, Seger R (2004). "MEK5 and ERK5 are localized in the nuclei of resting as well as stimulated cells, while MEKK2 translocates from the cytosol to the nucleus upon stimulation". J. Cell. Sci.117 (Pt 9): 1773–84. doi:10.1242/jcs.01040. PMID15075238.
1wi0: Solution structure of the PB1 domain of mouse mitogen activated protein kinase kinase 5 (MAP2K5)
2npt: Crystal Structure of the complex of human mitogen activated protein kinase kinase 5 phox domain (MAP2K5-phox) with human mitogen activated protein kinase kinase kinase 2 phox domain (MAP3K2-phox)
2o2v: Crystal Structure of the Complex of Human Mitogen Activated Protein Kinase Kinase 5 Phox Domain (MAP2K5-phox) with Human Mitogen Activated Protein Kinase Kinase Kinase 3 (MAP3K3B-phox)