# MAP2K6

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Protein-coding gene in the species Homo sapiens

Main article: [Mitogen-activated protein kinase kinase](/source/Mitogen-activated_protein_kinase_kinase)

MAP2K6 Available structures PDB Ortholog search: PDBe RCSB List of PDB id codes 2Y8O, 3ENM, 3FME, 3VN9 Identifiers Aliases MAP2K6, MAPKK6, MEK6, MKK6, PRKMK6, SAPKK-3, SAPKK3, mitogen-activated protein kinase kinase 6 External IDs OMIM: 601254; MGI: 1346870; HomoloGene: 55686; GeneCards: MAP2K6; OMA:MAP2K6 - orthologs Gene location (Human) Chr. Chromosome 17 (human)[1] Band 17q24.3 Start 69,414,697 bp[1] End 69,553,865 bp[1] Gene location (Mouse) Chr. Chromosome 11 (mouse)[2] Band 11|11 E1-E2 Start 110,399,122 bp[2] End 110,525,522 bp[2] RNA expression pattern Bgee Human Mouse (ortholog) Top expressed in rectum mucosa of transverse colon biceps brachii vastus lateralis muscle Skeletal muscle tissue of biceps brachii gastrocnemius muscle triceps brachii muscle deltoid muscle Skeletal muscle tissue of rectus abdominis muscle of thigh Top expressed in triceps brachii muscle temporal muscle muscle of thigh sternocleidomastoid muscle maxillary prominence somite mandibular prominence vastus lateralis muscle tail of embryo gastrocnemius muscle More reference expression data BioGPS More reference expression data Gene ontology Molecular function transferase activity nucleotide binding protein kinase activity kinase activity protein binding protein tyrosine kinase activity ATP binding protein kinase binding protein serine/threonine kinase activity identical protein binding MAP kinase kinase activity Cellular component cytoplasm nucleoplasm cytoskeleton nucleus cytosol Biological process positive regulation of protein phosphorylation regulation of transcription, DNA-templated cardiac muscle contraction phosphorylation cellular response to sorbitol positive regulation of nitric-oxide synthase biosynthetic process ovulation cycle process transcription, DNA-templated MAPK cascade protein phosphorylation positive regulation of prostaglandin secretion response to ischemia DNA damage induced protein phosphorylation positive regulation of apoptotic process peptidyl-tyrosine phosphorylation nucleotide-binding oligomerization domain containing signaling pathway signal transduction apoptotic process regulation of mitotic cell cycle stress-activated protein kinase signaling cascade activation of protein kinase activity regulation of apoptotic process negative regulation of cold-induced thermogenesis Sources:Amigo / QuickGO Orthologs Species Human Mouse Entrez 5608 26399 Ensembl ENSG00000108984 ENSMUSG00000020623 UniProt P52564 P70236 RefSeq (mRNA) NM_002758 NM_031988 NM_001330450 NM_011943 RefSeq (protein) NP_001317379 NP_002749 NP_036073 NP_001343274 NP_001343275 NP_001343276 NP_001343281 NP_001343282 Location (UCSC) Chr 17: 69.41 – 69.55 Mb Chr 11: 110.4 – 110.53 Mb PubMed search [3] [4] Wikidata View/Edit Human View/Edit Mouse

**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](/source/Enzyme) that in humans is encoded by the *MAP2K6* [gene](/source/Gene), on [chromosome 17](/source/Chromosome_17).[5]

## Function

MAPKK 6 is a member of the dual specificity protein kinase family, which functions as a [mitogen-activated protein](/source/Mitogen-activated_protein) (MAP) kinase kinase. [MAP kinases](/source/MAP_kinases), also known as [extracellular signal-regulated kinases](/source/Extracellular_signal-regulated_kinases) (ERKs), act as an integration point for multiple biochemical signals. This protein [phosphorylates](/source/Phosphorylates) and activates [p38 MAP kinase](/source/P38_mitogen-activated_protein_kinases) in response to inflammatory [cytokines](/source/Cytokines) or environmental stress. As an essential component of p38 MAP kinase mediated [signal transduction pathway](/source/Signal_transduction_pathway), this gene is involved in many cellular processes such as [stress-induced cell cycle arrest](https://en.wikipedia.org/w/index.php?title=Stress-induced_cell_cycle_arrest&action=edit&redlink=1), [transcription](/source/Transcription_(genetics)) activation and [apoptosis](/source/Apoptosis).[6]

## Interactions

MAP2K6 has been shown to [interact](/source/Protein-protein_interaction) with [TAOK2](/source/TAOK2),[7] [ASK1](/source/ASK1),[8][9] [MAPK14](/source/MAPK14)[7][10][11][12] and [MAP3K7](/source/MAP3K7).[13][14][15][16]

## References

1. ^ [***a***](#cite_ref-refGRCh38Ensembl_1-0) [***b***](#cite_ref-refGRCh38Ensembl_1-1) [***c***](#cite_ref-refGRCh38Ensembl_1-2) [GRCh38: Ensembl release 89: ENSG00000108984](http://May2017.archive.ensembl.org/Homo_sapiens/Gene/Summary?db=core;g=ENSG00000108984) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. ^ [***a***](#cite_ref-refGRCm38Ensembl_2-0) [***b***](#cite_ref-refGRCm38Ensembl_2-1) [***c***](#cite_ref-refGRCm38Ensembl_2-2) [GRCm38: Ensembl release 89: ENSMUSG00000020623](http://May2017.archive.ensembl.org/Mus_musculus/Gene/Summary?db=core;g=ENSMUSG00000020623) – [Ensembl](/source/Ensembl_genome_database_project), May 2017

1. **[^](#cite_ref-3)** ["Human PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=5608). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-4)** ["Mouse PubMed Reference:"](https://www.ncbi.nlm.nih.gov/sites/entrez?db=gene&cmd=Link&LinkName=gene_pubmed&from_uid=26399). *National Center for Biotechnology Information, U.S. National Library of Medicine*.

1. **[^](#cite_ref-pmid8621675_5-0)** 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)"](https://doi.org/10.1074%2Fjbc.271.6.2886). *The Journal of Biological Chemistry*. **271** (6): 2886–91. [doi](/source/Doi_(identifier)):[10.1074/jbc.271.6.2886](https://doi.org/10.1074%2Fjbc.271.6.2886). [PMID](/source/PMID_(identifier)) [8621675](https://pubmed.ncbi.nlm.nih.gov/8621675).

1. **[^](#cite_ref-entrez_6-0)** ["Entrez Gene: MAP2K6 mitogen-activated protein kinase kinase 6"](https://www.ncbi.nlm.nih.gov/gene?Db=gene&Cmd=ShowDetailView&TermToSearch=5608).

1. ^ [***a***](#cite_ref-pmid11279118_7-0) [***b***](#cite_ref-pmid11279118_7-1) Chen Z, Cobb MH (May 2001). ["Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2"](https://doi.org/10.1074%2Fjbc.M100681200). *The Journal of Biological Chemistry*. **276** (19): 16070–5. [doi](/source/Doi_(identifier)):[10.1074/jbc.M100681200](https://doi.org/10.1074%2Fjbc.M100681200). [PMID](/source/PMID_(identifier)) [11279118](https://pubmed.ncbi.nlm.nih.gov/11279118).

1. **[^](#cite_ref-pmid12820963_8-0)** 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)"](https://doi.org/10.1016%2FS1097-2765%2803%2900180-1). *Molecular Cell*. **11** (6): 1491–501. [doi](/source/Doi_(identifier)):[10.1016/S1097-2765(03)00180-1](https://doi.org/10.1016%2FS1097-2765%2803%2900180-1). [PMID](/source/PMID_(identifier)) [12820963](https://pubmed.ncbi.nlm.nih.gov/12820963).

1. **[^](#cite_ref-pmid11689443_9-0)** 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"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC125685). *The EMBO Journal*. **20** (21): 6028–36. [doi](/source/Doi_(identifier)):[10.1093/emboj/20.21.6028](https://doi.org/10.1093%2Femboj%2F20.21.6028). [PMC](/source/PMC_(identifier)) [125685](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC125685). [PMID](/source/PMID_(identifier)) [11689443](https://pubmed.ncbi.nlm.nih.gov/11689443).

1. **[^](#cite_ref-pmid12697810_10-0)** 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"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC153192). *Molecular and Cellular Biology*. **23** (9): 3079–90. [doi](/source/Doi_(identifier)):[10.1128/MCB.23.9.3079-3090.2003](https://doi.org/10.1128%2FMCB.23.9.3079-3090.2003). [PMC](/source/PMC_(identifier)) [153192](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC153192). [PMID](/source/PMID_(identifier)) [12697810](https://pubmed.ncbi.nlm.nih.gov/12697810).

1. **[^](#cite_ref-pmid8622669_11-0)** 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"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC231107). *Molecular and Cellular Biology*. **16** (3): 1247–55. [doi](/source/Doi_(identifier)):[10.1128/mcb.16.3.1247](https://doi.org/10.1128%2Fmcb.16.3.1247). [PMC](/source/PMC_(identifier)) [231107](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC231107). [PMID](/source/PMID_(identifier)) [8622669](https://pubmed.ncbi.nlm.nih.gov/8622669).

1. **[^](#cite_ref-pmid8626699_12-0)** 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"](https://doi.org/10.1074%2Fjbc.271.19.11427). *The Journal of Biological Chemistry*. **271** (19): 11427–33. [doi](/source/Doi_(identifier)):[10.1074/jbc.271.19.11427](https://doi.org/10.1074%2Fjbc.271.19.11427). [PMID](/source/PMID_(identifier)) [8626699](https://pubmed.ncbi.nlm.nih.gov/8626699).

1. **[^](#cite_ref-pmid14633987_13-0)** Ishitani T, Takaesu G, Ninomiya-Tsuji J, Shibuya H, [Gaynor RB](/source/Richard_Gaynor), Matsumoto K (Dec 2003). ["Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC291846). *The EMBO Journal*. **22** (23): 6277–88. [doi](/source/Doi_(identifier)):[10.1093/emboj/cdg605](https://doi.org/10.1093%2Femboj%2Fcdg605). [PMC](/source/PMC_(identifier)) [291846](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC291846). [PMID](/source/PMID_(identifier)) [14633987](https://pubmed.ncbi.nlm.nih.gov/14633987).

1. **[^](#cite_ref-pmid11460167_14-0)** 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. [Bibcode](/source/Bibcode_(identifier)):[2001Natur.412..346W](https://ui.adsabs.harvard.edu/abs/2001Natur.412..346W). [doi](/source/Doi_(identifier)):[10.1038/35085597](https://doi.org/10.1038%2F35085597). [PMID](/source/PMID_(identifier)) [11460167](https://pubmed.ncbi.nlm.nih.gov/11460167). [S2CID](/source/S2CID_(identifier)) [9641806](https://api.semanticscholar.org/CorpusID:9641806).

1. **[^](#cite_ref-pmid10094049_15-0)** 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. [Bibcode](/source/Bibcode_(identifier)):[1999Natur.398..252N](https://ui.adsabs.harvard.edu/abs/1999Natur.398..252N). [doi](/source/Doi_(identifier)):[10.1038/18465](https://doi.org/10.1038%2F18465). [PMID](/source/PMID_(identifier)) [10094049](https://pubmed.ncbi.nlm.nih.gov/10094049). [S2CID](/source/S2CID_(identifier)) [4421236](https://api.semanticscholar.org/CorpusID:4421236).

1. **[^](#cite_ref-pmid10838074_16-0)** 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. [Bibcode](/source/Bibcode_(identifier)):[2000FEBSL.474..141S](https://ui.adsabs.harvard.edu/abs/2000FEBSL.474..141S). [doi](/source/Doi_(identifier)):[10.1016/S0014-5793(00)01588-X](https://doi.org/10.1016%2FS0014-5793%2800%2901588-X). [PMID](/source/PMID_(identifier)) [10838074](https://pubmed.ncbi.nlm.nih.gov/10838074). [S2CID](/source/S2CID_(identifier)) [30831863](https://api.semanticscholar.org/CorpusID:30831863).

## Further reading

- Ben-Levy R, Hooper S, Wilson R, Paterson HF, Marshall CJ (Sep 1998). ["Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2"](https://doi.org/10.1016%2FS0960-9822%2898%2970442-7). *Current Biology*. **8** (19): 1049–57. [Bibcode](/source/Bibcode_(identifier)):[1998CBio....8.1049B](https://ui.adsabs.harvard.edu/abs/1998CBio....8.1049B). [doi](/source/Doi_(identifier)):[10.1016/S0960-9822(98)70442-7](https://doi.org/10.1016%2FS0960-9822%2898%2970442-7). [PMID](/source/PMID_(identifier)) [9768359](https://pubmed.ncbi.nlm.nih.gov/9768359). [S2CID](/source/S2CID_(identifier)) [15627349](https://api.semanticscholar.org/CorpusID:15627349).

- Tanaka S, Nakamura K, Takahasi N, Suda T (Dec 2005). "Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system". *Immunological Reviews*. **208**: 30–49. [doi](/source/Doi_(identifier)):[10.1111/j.0105-2896.2005.00327.x](https://doi.org/10.1111%2Fj.0105-2896.2005.00327.x). [PMID](/source/PMID_(identifier)) [16313339](https://pubmed.ncbi.nlm.nih.gov/16313339). [S2CID](/source/S2CID_(identifier)) [13811917](https://api.semanticscholar.org/CorpusID:13811917).

- Doza YN, Cuenda A, Thomas GM, Cohen P, Nebreda AR (May 1995). "Activation of the MAP kinase homologue RK requires the phosphorylation of Thr-180 and Tyr-182 and both residues are phosphorylated in chemically stressed KB cells". *FEBS Letters*. **364** (2): 223–8. [Bibcode](/source/Bibcode_(identifier)):[1995FEBSL.364..223D](https://ui.adsabs.harvard.edu/abs/1995FEBSL.364..223D). [doi](/source/Doi_(identifier)):[10.1016/0014-5793(95)00346-B](https://doi.org/10.1016%2F0014-5793%2895%2900346-B). [PMID](/source/PMID_(identifier)) [7750576](https://pubmed.ncbi.nlm.nih.gov/7750576). [S2CID](/source/S2CID_(identifier)) [25025858](https://api.semanticscholar.org/CorpusID:25025858).

- Maruyama K, Sugano S (Jan 1994). "Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides". *Gene*. **138** (1–2): 171–4. [doi](/source/Doi_(identifier)):[10.1016/0378-1119(94)90802-8](https://doi.org/10.1016%2F0378-1119%2894%2990802-8). [PMID](/source/PMID_(identifier)) [8125298](https://pubmed.ncbi.nlm.nih.gov/8125298).

- 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"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC231107). *Molecular and Cellular Biology*. **16** (3): 1247–55. [doi](/source/Doi_(identifier)):[10.1128/mcb.16.3.1247](https://doi.org/10.1128%2Fmcb.16.3.1247). [PMC](/source/PMC_(identifier)) [231107](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC231107). [PMID](/source/PMID_(identifier)) [8622669](https://pubmed.ncbi.nlm.nih.gov/8622669).

- 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"](https://doi.org/10.1074%2Fjbc.271.19.11427). *The Journal of Biological Chemistry*. **271** (19): 11427–33. [doi](/source/Doi_(identifier)):[10.1074/jbc.271.19.11427](https://doi.org/10.1074%2Fjbc.271.19.11427). [PMID](/source/PMID_(identifier)) [8626699](https://pubmed.ncbi.nlm.nih.gov/8626699).

- Moriguchi T, Kuroyanagi N, Yamaguchi K, Gotoh Y, Irie K, Kano T, Shirakabe K, Muro Y, Shibuya H, Matsumoto K, Nishida E, Hagiwara M (Jun 1996). ["A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3"](https://doi.org/10.1074%2Fjbc.271.23.13675). *The Journal of Biological Chemistry*. **271** (23): 13675–9. [doi](/source/Doi_(identifier)):[10.1074/jbc.271.23.13675](https://doi.org/10.1074%2Fjbc.271.23.13675). [PMID](/source/PMID_(identifier)) [8663074](https://pubmed.ncbi.nlm.nih.gov/8663074).

- Cuenda A, Alonso G, Morrice N, Jones M, Meier R, Cohen P, Nebreda AR (Aug 1996). ["Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress- and cytokine-stimulated monocytes and epithelial cells"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC452138). *The EMBO Journal*. **15** (16): 4156–64. [doi](/source/Doi_(identifier)):[10.1002/j.1460-2075.1996.tb00790.x](https://doi.org/10.1002%2Fj.1460-2075.1996.tb00790.x). [PMC](/source/PMC_(identifier)) [452138](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC452138). [PMID](/source/PMID_(identifier)) [8861944](https://pubmed.ncbi.nlm.nih.gov/8861944).

- Goedert M, Cuenda A, Craxton M, Jakes R, Cohen P (Jun 1997). ["Activation of the novel stress-activated protein kinase SAPK4 by cytokines and cellular stresses is mediated by SKK3 (MKK6); comparison of its substrate specificity with that of other SAP kinases"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1169981). *The EMBO Journal*. **16** (12): 3563–71. [doi](/source/Doi_(identifier)):[10.1093/emboj/16.12.3563](https://doi.org/10.1093%2Femboj%2F16.12.3563). [PMC](/source/PMC_(identifier)) [1169981](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1169981). [PMID](/source/PMID_(identifier)) [9218798](https://pubmed.ncbi.nlm.nih.gov/9218798).

- Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S (Oct 1997). "Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library". *Gene*. **200** (1–2): 149–56. [doi](/source/Doi_(identifier)):[10.1016/S0378-1119(97)00411-3](https://doi.org/10.1016%2FS0378-1119%2897%2900411-3). [PMID](/source/PMID_(identifier)) [9373149](https://pubmed.ncbi.nlm.nih.gov/9373149).

- Enslen H, Raingeaud J, Davis RJ (Jan 1998). ["Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6"](https://doi.org/10.1074%2Fjbc.273.3.1741). *The Journal of Biological Chemistry*. **273** (3): 1741–8. [doi](/source/Doi_(identifier)):[10.1074/jbc.273.3.1741](https://doi.org/10.1074%2Fjbc.273.3.1741). [PMID](/source/PMID_(identifier)) [9430721](https://pubmed.ncbi.nlm.nih.gov/9430721).

- Chan-Hui PY, Weaver R (Dec 1998). ["Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase cascades"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1219910). *The Biochemical Journal*. **336** (Pt 3): 599–609. [doi](/source/Doi_(identifier)):[10.1042/bj3360599](https://doi.org/10.1042%2Fbj3360599). [PMC](/source/PMC_(identifier)) [1219910](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1219910). [PMID](/source/PMID_(identifier)) [9841871](https://pubmed.ncbi.nlm.nih.gov/9841871).

- Chen Z, Hutchison M, Cobb MH (Oct 1999). ["Isolation of the protein kinase TAO2 and identification of its mitogen-activated protein kinase/extracellular signal-regulated kinase kinase binding domain"](https://doi.org/10.1074%2Fjbc.274.40.28803). *The Journal of Biological Chemistry*. **274** (40): 28803–7. [doi](/source/Doi_(identifier)):[10.1074/jbc.274.40.28803](https://doi.org/10.1074%2Fjbc.274.40.28803). [PMID](/source/PMID_(identifier)) [10497253](https://pubmed.ncbi.nlm.nih.gov/10497253).

- Cong F, Goff SP (Nov 1999). ["c-Abl-induced apoptosis, but not cell cycle arrest, requires mitogen-activated protein kinase kinase 6 activation"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC24148). *Proceedings of the National Academy of Sciences of the United States of America*. **96** (24): 13819–24. [Bibcode](/source/Bibcode_(identifier)):[1999PNAS...9613819C](https://ui.adsabs.harvard.edu/abs/1999PNAS...9613819C). [doi](/source/Doi_(identifier)):[10.1073/pnas.96.24.13819](https://doi.org/10.1073%2Fpnas.96.24.13819). [PMC](/source/PMC_(identifier)) [24148](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC24148). [PMID](/source/PMID_(identifier)) [10570156](https://pubmed.ncbi.nlm.nih.gov/10570156).

- Wang X, McGowan CH, Zhao M, He L, Downey JS, Fearns C, Wang Y, Huang S, Han J (Jul 2000). ["Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC85840). *Molecular and Cellular Biology*. **20** (13): 4543–52. [doi](/source/Doi_(identifier)):[10.1128/MCB.20.13.4543-4552.2000](https://doi.org/10.1128%2FMCB.20.13.4543-4552.2000). [PMC](/source/PMC_(identifier)) [85840](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC85840). [PMID](/source/PMID_(identifier)) [10848581](https://pubmed.ncbi.nlm.nih.gov/10848581).

- Visconti R, Gadina M, Chiariello M, Chen EH, Stancato LF, Gutkind JS, O'Shea JJ (Sep 2000). "Importance of the MKK6/p38 pathway for interleukin-12-induced STAT4 serine phosphorylation and transcriptional activity". *Blood*. **96** (5): 1844–52. [doi](/source/Doi_(identifier)):[10.1182/blood.V96.5.1844](https://doi.org/10.1182%2Fblood.V96.5.1844). [PMID](/source/PMID_(identifier)) [10961885](https://pubmed.ncbi.nlm.nih.gov/10961885).

- Fleming Y, Armstrong CG, Morrice N, Paterson A, Goedert M, Cohen P (Nov 2000). ["Synergistic activation of stress-activated protein kinase 1/c-Jun N-terminal kinase (SAPK1/JNK) isoforms by mitogen-activated protein kinase kinase 4 (MKK4) and MKK7"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1221441). *The Biochemical Journal*. 352 Pt 1 (Pt 1): 145–54. [doi](/source/Doi_(identifier)):[10.1042/0264-6021:3520145](https://doi.org/10.1042%2F0264-6021%3A3520145). [PMC](/source/PMC_(identifier)) [1221441](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1221441). [PMID](/source/PMID_(identifier)) [11062067](https://pubmed.ncbi.nlm.nih.gov/11062067).

- Vitale G, Bernardi L, Napolitani G, Mock M, Montecucco C (Dec 2000). ["Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor"](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1221512). *The Biochemical Journal*. 352 Pt 3 (Pt 3): 739–45. [doi](/source/Doi_(identifier)):[10.1042/0264-6021:3520739](https://doi.org/10.1042%2F0264-6021%3A3520739). [PMC](/source/PMC_(identifier)) [1221512](https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1221512). [PMID](/source/PMID_(identifier)) [11104681](https://pubmed.ncbi.nlm.nih.gov/11104681).

v t e Kinases: Serine/threonine-specific protein kinases (EC 2.7.11-12) Serine/threonine-specific protein kinases (EC 2.7.11.1-EC 2.7.11.20) Non-specific serine/threonine protein kinases (EC 2.7.11.1) LATS1 LATS2 MAST1 MAST2 STK38 STK38L CIT ROCK1 SGK SGK2 SGK3 Protein kinase B AKT1 AKT2 AKT3 Ataxia telangiectasia mutated mTOR EIF-2 kinases PKR HRI EIF2AK3 EIF2AK4 Wee1 WEE1 Pyruvate dehydrogenase kinase (EC 2.7.11.2) PDK1 PDK2 PDK3 PDK4 Dephospho-(reductase kinase) kinase (EC 2.7.11.3) AMP-activated protein kinase α PRKAA1 PRKAA2 β PRKAB1 PRKAB2 γ PRKAG1 PRKAG2 PRKAG3 3-methyl-2-oxobutanoate dehydrogenase (acetyl-transferring) kinase (EC 2.7.11.4) BCKDK BCKDHA BCKDHB (isocitrate dehydrogenase (NADP+)) kinase (EC 2.7.11.5) IDH2 IDH3A IDH3B IDH3G (tyrosine 3-monooxygenase) kinase (EC 2.7.11.6) STK4 Myosin-heavy-chain kinase (EC 2.7.11.7) Aurora kinase Aurora kinase A Aurora kinase B Aurora kinase C Fas-activated serine/threonine kinase (EC 2.7.11.8) FASTK STK10 Goodpasture-antigen-binding protein kinase (EC 2.7.11.9) - IκB kinase (EC 2.7.11.10) CHUK IKK2 TBK1 IKBKE IKBKG IKBKAP cAMP-dependent protein kinase (EC 2.7.11.11) Protein kinase A PRKACG PRKACB PRKACA PRKY cGMP-dependent protein kinase (EC 2.7.11.12) Protein kinase G PRKG1 Protein kinase C (EC 2.7.11.13) Protein kinase C Protein kinase Cζ PKC alpha PRKCB1 PRKCD PRKCE PRKCH PRKCG PRKCI PRKCQ Protein kinase N1 PKN2 PKN3 Rhodopsin kinase (EC 2.7.11.14) Rhodopsin kinase Beta adrenergic receptor kinase (EC 2.7.11.15) Beta adrenergic receptor kinase Beta adrenergic receptor kinase-2 G-protein coupled receptor kinases (EC 2.7.11.16) GRK4 GRK5 GRK6 Ca2+/calmodulin-dependent (EC 2.7.11.17) BRSK2 CAMK1 CAMK1A CAMK1B CAMK1D CAMK1G CAMK2 CAMK2A CAMK2B CAMK2D CAMK2G CAMK4 MLCK CASK CHEK1 CHEK2 DAPK1 DAPK2 DAPK3 STK11 MAPKAPK2 MAPKAPK3 MAPKAPK5 MARK1 MARK2 MARK3 MARK4 MELK MKNK1 MKNK2 NUAK1 NUAK2 OBSCN PASK PHKG1 PHKG2 PIM1 PIM2 PKD1 PRKD2 PRKD3 PSKH1 SNF1LK2 KIAA0999 STK40 SNF1LK SNRK SPEG TSSK2 Kalirin TRIB1 TRIB2 TRIB3 TRIO Titin DCLK1 Myosin light-chain kinase (EC 2.7.11.18) MYLK MYLK2 MYLK3 MYLK4 Phosphorylase kinase (EC 2.7.11.19) PHKA1 PHKA2 PHKB PHKG1 PHKG2 Elongation factor 2 kinase (EC 2.7.11.20) EEF2K STK19 Polo kinase (EC 2.7.11.21) PLK1 PLK2 PLK3 PLK4 Serine/threonine-specific protein kinases (EC 2.7.11.21-EC 2.7.11.30) Polo kinase (EC 2.7.11.21) PLK1 PLK2 PLK3 PLK4 Cyclin-dependent kinase (EC 2.7.11.22) CDK1 CDK2 CDKL2 CDK3 CDK4 CDK5 CDKL5 CDK6 CDK7 CDK8 CDK9 CDK10 CDK12 CDC2L5 PCTK1 PCTK2 PCTK3 PFTK1 CDC2L1 (RNA-polymerase)-subunit kinase (EC 2.7.11.23) RPS6KA5 RPS6KA4 P70-S6 Kinase 1 RPS6KB2 RPS6KA2 RPS6KA3 RPS6KA1 RPS6KC1 Mitogen-activated protein kinase (EC 2.7.11.24) Extracellular signal-regulated MAPK1 MAPK3 MAPK4 MAPK6 MAPK7 MAPK12 MAPK15 C-Jun N-terminal MAPK8 MAPK9 MAPK10 P38 mitogen-activated protein MAPK11 MAPK13 MAPK14 MAP3K (EC 2.7.11.25) MAP kinase kinase kinases MAP3K1 MAP3K2 MAP3K3 MAP3K4 MAP3K5 MAP3K6 MAP3K7 MAP3K8 RAFs ARAF BRAF KSR1 KSR2 MLKs MAP3K12 MAP3K13 MAP3K9 MAP3K10 MAP3K11 MAP3K7 ZAK CDC7 MAP3K14 Tau-protein kinase (EC 2.7.11.26) TPK1 TTK GSK-3 (acetyl-CoA carboxylase) kinase (EC 2.7.11.27) - Tropomyosin kinase (EC 2.7.11.28) - Low-density-lipoprotein receptor kinase (EC 2.7.11.29) - Receptor protein serine/threonine kinase (EC 2.7.11.30) Bone morphogenetic protein receptors BMPR1 BMPR1A BMPR1B BMPR2 ACVR1 ACVR1B ACVR1C ACVR2A ACVR2B ACVRL1 Anti-Müllerian hormone receptor Dual-specificity kinases (EC 2.7.12) MAP2K MAP2K1 MAP2K2 MAP2K3 MAP2K4 MAP2K5 MAP2K6 MAP2K7

v t e Enzymes Activity Active site Binding site Catalytic triad Oxyanion hole Enzyme promiscuity Diffusion-limited enzyme Cofactor Enzyme catalysis Regulation Allosteric regulation Cooperativity Enzyme inhibitor Enzyme activator Classification EC number Enzyme superfamily Enzyme family List of enzymes Kinetics Enzyme kinetics Eadie–Hofstee diagram Hanes–Woolf plot Lineweaver–Burk plot Michaelis–Menten kinetics Types EC1 Oxidoreductases (list) EC2 Transferases (list) EC3 Hydrolases (list) EC4 Lyases (list) EC5 Isomerases (list) EC6 Ligases (list) EC7 Translocases (list)

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Adapted from the Wikipedia article [MAP2K6](https://en.wikipedia.org/wiki/MAP2K6) by Wikipedia contributors ([contributor history](https://en.wikipedia.org/wiki/MAP2K6?action=history)). Available under [Creative Commons Attribution-ShareAlike 4.0 International](https://creativecommons.org/licenses/by-sa/4.0/). Changes may have been made.