Biology:MAP2K5

Short description: Protein-coding gene in the species Homo sapiens

Generic protein structure example

Dual specificity mitogen-activated protein kinase kinase 5 is an enzyme that in humans is encoded by the MAP2K5 gene.

Function

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.

Upstream

This kinase itself can be phosphorylated and activated by MAP3K3/MEKK3, as well as by atypical protein kinase C isoforms (aPKCs).

Downstream

This kinase specifically interacts with and activates MAPK7/ERK5.

Interactions

MAP2K5 has been shown to interact with MAPK7, MAP3K2, Protein kinase Mζ and MAP3K3.

Further reading

• "Isolation of MEK5 and differential expression of alternatively spliced forms". The Journal of Biological Chemistry 270 (48): 28897–902. Dec 1995. doi:10.1074/jbc.270.48.28897. PMID 7499418. 
• "BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C". The EMBO Journal 16 (23): 7054–66. Dec 1997. doi:10.1093/emboj/16.23.7054. PMID 9384584. 
• "Bmk1/Erk5 is required for cell proliferation induced by epidermal growth factor". Nature 395 (6703): 713–6. Oct 1998. doi:10.1038/27234. PMID 9790194. Bibcode: 1998Natur.395..713K. 
• "Contribution of the ERK5/MEK5 pathway to Ras/Raf signaling and growth control". The Journal of Biological Chemistry 274 (44): 31588–92. Oct 1999. doi:10.1074/jbc.274.44.31588. PMID 10531364. 
• "MEKK3 directly regulates MEK5 activity as part of the big mitogen-activated protein kinase 1 (BMK1) signaling pathway". The Journal of Biological Chemistry 274 (51): 36035–8. Dec 1999. doi:10.1074/jbc.274.51.36035. PMID 10593883. 
• "MEKK2 associates with the adapter protein Lad/RIBP and regulates the MEK5-BMK1/ERK5 pathway". The Journal of Biological Chemistry 276 (7): 5093–100. Feb 2001. doi:10.1074/jbc.M003719200. PMID 11073940. 
• "MEK5, a new target of the atypical protein kinase C isoforms in mitogenic signaling". Molecular and Cellular Biology 21 (4): 1218–27. Feb 2001. doi:10.1128/MCB.21.4.1218-1227.2001. PMID 11158308. 
• "Activated MEK5 induces serial assembly of sarcomeres and eccentric cardiac hypertrophy". The EMBO Journal 20 (11): 2757–67. Jun 2001. doi:10.1093/emboj/20.11.2757. PMID 11387209. 
• "Extracellular signal regulated kinase 5 (ERK5) is required for the differentiation of muscle cells". EMBO Reports 2 (9): 829–34. Sep 2001. doi:10.1093/embo-reports/kve177. PMID 11520859. 
• "Identification of mitogen-activated protein kinase kinase as a chemoresistant pathway in MCF-7 cells by using gene expression microarray". Surgery 132 (2): 293–301. Aug 2002. doi:10.1067/msy.2002.125389. PMID 12219026. 
• "MEK5 overexpression is associated with metastatic prostate cancer, and stimulates proliferation, MMP-9 expression and invasion". Oncogene 22 (9): 1381–9. Mar 2003. doi:10.1038/sj.onc.1206154. PMID 12618764. 
• "An analysis of the phosphorylation and activation of extracellular-signal-regulated protein kinase 5 (ERK5) by mitogen-activated protein kinase kinase 5 (MKK5) in vitro". The Biochemical Journal 372 (Pt 2): 567–75. Jun 2003. doi:10.1042/BJ20030193. PMID 12628002. 
• "Mutations in protein kinase subdomain X differentially affect MEKK2 and MEKK1 activity". Biochemical and Biophysical Research Communications 303 (2): 532–40. Apr 2003. doi:10.1016/S0006-291X(03)00387-5. PMID 12659851. 
• "Interaction codes within the family of mammalian Phox and Bem1p domain-containing proteins". The Journal of Biological Chemistry 278 (36): 34568–81. Sep 2003. doi:10.1074/jbc.M303221200. PMID 12813044. 
• "Differential role of MEK5alpha and MEK5beta in BMK1/ERK5 activation". The Journal of Biological Chemistry 279 (2): 1506–12. Jan 2004. doi:10.1074/jbc.M308755200. PMID 14583600. 
• "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology 6 (2): 97–105. Feb 2004. doi:10.1038/ncb1086. PMID 14743216. 
• "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". Journal of Cell Science 117 (Pt 9): 1773–84. Apr 2004. doi:10.1242/jcs.01040. PMID 15075238.