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Mitogen-activated protein kinase kinase 6
Protein MAP2K6 PDB 3ENM.png
Rendering based on PDB 3ENM.
Available structures
PDB Ortholog search: PDBe, RCSB
External IDs OMIM601254 MGI1346870 HomoloGene55686 ChEMBL: 2171 GeneCards: MAP2K6 Gene
EC number
RNA expression pattern
PBB GE MAP2K6 205698 s at tn.png
PBB GE MAP2K6 205699 at tn.png
More reference expression data
Species Human Mouse
Entrez 5608 26399
Ensembl ENSG00000108984 ENSMUSG00000020623
UniProt P52564 P70236
RefSeq (mRNA) NM_002758 NM_011943
RefSeq (protein) NP_002749 NP_036073
Location (UCSC) Chr 17:
69.41 – 69.54 Mb
Chr 11:
110.4 – 110.53 Mb
PubMed search [1] [2]

Dual specificity mitogen-activated protein kinase kinase 6 also known as MAP kinase kinase 6 (MAPKK 6) or MAPK/ERK kinase 6 is an enzyme that in humans is encoded by the MAP2K6 gene, on chromosome 17.[1]


MAPKK 6 is a member of the dual specificity protein kinase family, which functions as a mitogen-activated protein (MAP) kinase kinase. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act as an integration point for multiple biochemical signals. This protein phosphorylates and activates p38 MAP kinase in response to inflammatory cytokines or environmental stress. As an essential component of p38 MAP kinase mediated signal transduction pathway, this gene is involved in many cellular processes such as stress-induced cell cycle arrest, transcription activation and apoptosis.[2]


MAP2K6 has been shown to interact with TAOK2,[3] ASK1,[4][5] MAPK14[3][6][7][8] and MAP3K7.[9][10][11][12]


  1. ^ Han J, Lee JD, Jiang Y, Li Z, Feng L, Ulevitch RJ (Feb 1996). "Characterization of the structure and function of a novel MAP kinase kinase (MKK6)". The Journal of Biological Chemistry 271 (6): 2886–91. doi:10.1074/jbc.271.6.2886. PMID 8621675. 
  2. ^ "Entrez Gene: MAP2K6 mitogen-activated protein kinase kinase 6". 
  3. ^ a b Chen Z, Cobb MH (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". The Journal of Biological Chemistry 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118. 
  4. ^ Huang S, Shu L, Dilling MB, Easton J, Harwood FC, Ichijo H, Houghton PJ (Jun 2003). "Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/p21(Cip1)". Molecular Cell 11 (6): 1491–501. doi:10.1016/S1097-2765(03)00180-1. PMID 12820963. 
  5. ^ Morita K, Saitoh M, Tobiume K, Matsuura H, Enomoto S, Nishitoh H, Ichijo H (Nov 2001). "Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress". The EMBO Journal 20 (21): 6028–36. doi:10.1093/emboj/20.21.6028. PMC 125685. PMID 11689443. 
  6. ^ Sanz-Moreno V, Casar B, Crespo P (May 2003). "p38alpha isoform Mxi2 binds to extracellular signal-regulated kinase 1 and 2 mitogen-activated protein kinase and regulates its nuclear activity by sustaining its phosphorylation levels". Molecular and Cellular Biology 23 (9): 3079–90. doi:10.1128/MCB.23.9.3079-3090.2003. PMC 153192. PMID 12697810. 
  7. ^ Raingeaud J, Whitmarsh AJ, Barrett T, Dérijard B, Davis RJ (Mar 1996). "MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway". Molecular and Cellular Biology 16 (3): 1247–55. PMC 231107. PMID 8622669. 
  8. ^ Stein B, Brady H, Yang MX, Young DB, Barbosa MS (May 1996). "Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade". The Journal of Biological Chemistry 271 (19): 11427–33. doi:10.1074/jbc.271.19.11427. PMID 8626699. 
  9. ^ Ishitani T, Takaesu G, Ninomiya-Tsuji J, Shibuya H, Gaynor RB, Matsumoto K (Dec 2003). "Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling". The EMBO Journal 22 (23): 6277–88. doi:10.1093/emboj/cdg605. PMC 291846. PMID 14633987. 
  10. ^ Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ (Jul 2001). "TAK1 is a ubiquitin-dependent kinase of MKK and IKK". Nature 412 (6844): 346–51. doi:10.1038/35085597. PMID 11460167. 
  11. ^ Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K (Mar 1999). "The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway". Nature 398 (6724): 252–6. doi:10.1038/18465. PMID 10094049. 
  12. ^ Sakurai H, Miyoshi H, Mizukami J, Sugita T (Jun 2000). "Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1". FEBS Letters 474 (2-3): 141–5. doi:10.1016/S0014-5793(00)01588-X. PMID 10838074. 

Further reading[edit]