MAP2K6: Difference between revisions

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{{main|Mitogen-activated protein kinase kinase}}
{{main|Mitogen-activated protein kinase kinase}}
<!-- The PBB_Controls template provides controls for Protein Box Bot, please see Template:PBB_Controls for details. -->
{{Infobox_gene}}
{{PBB_Controls
'''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]].<ref name="pmid8621675">{{cite journal | vauthors = Han J, Lee JD, Jiang Y, Li Z, Feng L, Ulevitch RJ | title = Characterization of the structure and function of a novel MAP kinase kinase (MKK6) | journal = The Journal of Biological Chemistry | volume = 271 | issue = 6 | pages = 2886–91 | date = Feb 1996 | pmid = 8621675 | pmc = | doi = 10.1074/jbc.271.6.2886 }}</ref>
| update_page = yes
| require_manual_inspection = no
| update_protein_box = yes
| update_summary = yes
| update_citations = yes
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<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== Function ==
{{GNF_Protein_box
| image =
| image_source =
| PDB =
| Name = Mitogen-activated protein kinase kinase 6
| HGNCid = 6846
| Symbol = MAP2K6
| AltSymbols =; MAPKK6; MEK6; MKK6; PRKMK6; SAPKK3
| OMIM = 601254
| ECnumber = 
| Homologene = 55686
| MGIid = 1346870
| GeneAtlas_image1 = PBB_GE_MAP2K6_205698_s_at_tn.png
| GeneAtlas_image2 = PBB_GE_MAP2K6_205699_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0004674 |text = protein serine/threonine kinase activity}} {{GNF_GO|id=GO:0004708 |text = MAP kinase kinase activity}} {{GNF_GO|id=GO:0004713 |text = protein-tyrosine kinase activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0016740 |text = transferase activity}}
| Component =
| Process = {{GNF_GO|id=GO:0000187 |text = activation of MAPK activity}} {{GNF_GO|id=GO:0006975 |text = DNA damage induced protein phosphorylation}} {{GNF_GO|id=GO:0007050 |text = cell cycle arrest}} {{GNF_GO|id=GO:0007165 |text = signal transduction}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 5608
    | Hs_Ensembl = ENSG00000108984
    | Hs_RefseqProtein = NP_002749
    | Hs_RefseqmRNA = NM_002758
    | Hs_GenLoc_db = 
    | Hs_GenLoc_chr = 17
    | Hs_GenLoc_start = 64922434
    | Hs_GenLoc_end = 65051067
    | Hs_Uniprot = P52564
    | Mm_EntrezGene = 26399
    | Mm_Ensembl = ENSMUSG00000020623
    | Mm_RefseqmRNA = NM_011943
    | Mm_RefseqProtein = NP_036073
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 11
    | Mm_GenLoc_start = 110215212
    | Mm_GenLoc_end = 110341612
    | Mm_Uniprot = P70273
  }}
}}
'''Mitogen-activated protein kinase kinase 6''', also known as '''MAP2K6''', is a human [[gene]].


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
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 mitogen-activated protein kinases|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 (genetics)|transcription]] activation and [[apoptosis]].<ref name="entrez">{{cite web | title = Entrez Gene: MAP2K6 mitogen-activated protein kinase kinase 6| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5608| accessdate = }}</ref>
{{PBB_Summary
| section_title =
| summary_text = This gene encodes 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.<ref name="entrez">{{cite web | title = Entrez Gene: MAP2K6 mitogen-activated protein kinase kinase 6| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5608| accessdate = }}</ref>
}}


==References==
== Interactions ==
{{reflist|2}}
 
==Further reading==
MAP2K6 has been shown to [[Protein-protein interaction|interact]] with [[TAOK2]],<ref name=pmid11279118>{{cite journal | vauthors = Chen Z, Cobb MH | title = Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2 | journal = The Journal of Biological Chemistry | volume = 276 | issue = 19 | pages = 16070–5 | date = May 2001 | pmid = 11279118 | doi = 10.1074/jbc.M100681200 }}</ref> [[ASK1]],<ref name=pmid12820963>{{cite journal | vauthors = Huang S, Shu L, Dilling MB, Easton J, Harwood FC, Ichijo H, Houghton PJ | title = Sustained activation of the JNK cascade and rapamycin-induced apoptosis are suppressed by p53/p21(Cip1) | journal = Molecular Cell | volume = 11 | issue = 6 | pages = 1491–501 | date = Jun 2003 | pmid = 12820963 | doi = 10.1016/S1097-2765(03)00180-1 }}</ref><ref name=pmid11689443>{{cite journal | vauthors = Morita K, Saitoh M, Tobiume K, Matsuura H, Enomoto S, Nishitoh H, Ichijo H | title = Negative feedback regulation of ASK1 by protein phosphatase 5 (PP5) in response to oxidative stress | journal = The EMBO Journal | volume = 20 | issue = 21 | pages = 6028–36 | date = Nov 2001 | pmid = 11689443 | pmc = 125685 | doi = 10.1093/emboj/20.21.6028 }}</ref> [[MAPK14]]<ref name=pmid11279118/><ref name=pmid12697810>{{cite journal | vauthors = Sanz-Moreno V, Casar B, Crespo P | title = 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 | journal = Molecular and Cellular Biology | volume = 23 | issue = 9 | pages = 3079–90 | date = May 2003 | pmid = 12697810 | pmc = 153192 | doi = 10.1128/MCB.23.9.3079-3090.2003 }}</ref><ref name=pmid8622669>{{cite journal | vauthors = Raingeaud J, Whitmarsh AJ, Barrett T, Dérijard B, Davis RJ | title = MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway | journal = Molecular and Cellular Biology | volume = 16 | issue = 3 | pages = 1247–55 | date = Mar 1996 | pmid = 8622669 | pmc = 231107 | doi=10.1128/mcb.16.3.1247}}</ref><ref name=pmid8626699>{{cite journal | vauthors = Stein B, Brady H, Yang MX, Young DB, Barbosa MS | title = Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade | journal = The Journal of Biological Chemistry | volume = 271 | issue = 19 | pages = 11427–33 | date = May 1996 | pmid = 8626699 | doi = 10.1074/jbc.271.19.11427 }}</ref> and [[MAP3K7]].<ref name=pmid14633987>{{cite journal | vauthors = Ishitani T, Takaesu G, Ninomiya-Tsuji J, Shibuya H, Gaynor RB, Matsumoto K | title = Role of the TAB2-related protein TAB3 in IL-1 and TNF signaling | journal = The EMBO Journal | volume = 22 | issue = 23 | pages = 6277–88 | date = Dec 2003 | pmid = 14633987 | pmc = 291846 | doi = 10.1093/emboj/cdg605 }}</ref><ref name=pmid11460167>{{cite journal | vauthors = Wang C, Deng L, Hong M, Akkaraju GR, Inoue J, Chen ZJ | title = TAK1 is a ubiquitin-dependent kinase of MKK and IKK | journal = Nature | volume = 412 | issue = 6844 | pages = 346–51 | date = Jul 2001 | pmid = 11460167 | doi = 10.1038/35085597 }}</ref><ref name=pmid10094049>{{cite journal | vauthors = Ninomiya-Tsuji J, Kishimoto K, Hiyama A, Inoue J, Cao Z, Matsumoto K | title = The kinase TAK1 can activate the NIK-I kappaB as well as the MAP kinase cascade in the IL-1 signalling pathway | journal = Nature | volume = 398 | issue = 6724 | pages = 252–6 | date = Mar 1999 | pmid = 10094049 | doi = 10.1038/18465 }}</ref><ref name=pmid10838074>{{cite journal | vauthors = Sakurai H, Miyoshi H, Mizukami J, Sugita T | title = Phosphorylation-dependent activation of TAK1 mitogen-activated protein kinase kinase kinase by TAB1 | journal = FEBS Letters | volume = 474 | issue = 2-3 | pages = 141–5 | date = Jun 2000 | pmid = 10838074 | doi = 10.1016/S0014-5793(00)01588-X }}</ref>
 
== References ==
{{reflist}}
 
== Further reading ==
{{refbegin | 2}}
{{refbegin | 2}}
{{PBB_Further_reading
* {{cite journal | vauthors = Ben-Levy R, Hooper S, Wilson R, Paterson HF, Marshall CJ | title = Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2 | journal = Current Biology | volume = 8 | issue = 19 | pages = 1049–57 | date = Sep 1998 | pmid = 9768359 | doi = 10.1016/S0960-9822(98)70442-7 }}
| citations =
* {{cite journal | vauthors = Tanaka S, Nakamura K, Takahasi N, Suda T | title = Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system | journal = Immunological Reviews | volume = 208 | issue =  | pages = 30–49 | date = Dec 2005 | pmid = 16313339 | doi = 10.1111/j.0105-2896.2005.00327.x }}
*{{cite journal | author=Ben-Levy R, Hooper S, Wilson R, ''et al.'' |title=Nuclear export of the stress-activated protein kinase p38 mediated by its substrate MAPKAP kinase-2. |journal=Curr. Biol. |volume=8 |issue= 19 |pages= 1049-57 |year= 1999 |pmid= 9768359 |doi= }}
* {{cite journal | vauthors = Doza YN, Cuenda A, Thomas GM, Cohen P, Nebreda AR | title = 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 | journal = FEBS Letters | volume = 364 | issue = 2 | pages = 223–8 | date = May 1995 | pmid = 7750576 | doi = 10.1016/0014-5793(95)00346-B }}
*{{cite journal | author=Tanaka S, Nakamura K, Takahasi N, Suda T |title=Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system. |journal=Immunol. Rev. |volume=208 |issue=  |pages= 30-49 |year= 2006 |pmid= 16313339 |doi= 10.1111/j.0105-2896.2005.00327.x }}
* {{cite journal | vauthors = Maruyama K, Sugano S | title = Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides | journal = Gene | volume = 138 | issue = 1-2 | pages = 171–4 | date = Jan 1994 | pmid = 8125298 | doi = 10.1016/0378-1119(94)90802-8 }}
*{{cite journal | author=Doza YN, Cuenda A, Thomas GM, ''et al.'' |title=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. |journal=FEBS Lett. |volume=364 |issue= 2 |pages= 223-8 |year= 1995 |pmid= 7750576 |doi= }}
* {{cite journal | vauthors = Raingeaud J, Whitmarsh AJ, Barrett T, Dérijard B, Davis RJ | title = MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway | journal = Molecular and Cellular Biology | volume = 16 | issue = 3 | pages = 1247–55 | date = Mar 1996 | pmid = 8622669 | pmc = 231107 | doi =  10.1128/mcb.16.3.1247}}
*{{cite journal | author=Maruyama K, Sugano S |title=Oligo-capping: a simple method to replace the cap structure of eukaryotic mRNAs with oligoribonucleotides. |journal=Gene |volume=138 |issue= 1-2 |pages= 171-4 |year= 1994 |pmid= 8125298 |doi= }}
* {{cite journal | vauthors = Stein B, Brady H, Yang MX, Young DB, Barbosa MS | title = Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade | journal = The Journal of Biological Chemistry | volume = 271 | issue = 19 | pages = 11427–33 | date = May 1996 | pmid = 8626699 | doi = 10.1074/jbc.271.19.11427 }}
*{{cite journal | author=Han J, Lee JD, Jiang Y, ''et al.'' |title=Characterization of the structure and function of a novel MAP kinase kinase (MKK6). |journal=J. Biol. Chem. |volume=271 |issue= 6 |pages= 2886-91 |year= 1996 |pmid= 8621675 |doi=  }}
* {{cite journal | vauthors = Moriguchi T, Kuroyanagi N, Yamaguchi K, Gotoh Y, Irie K, Kano T, Shirakabe K, Muro Y, Shibuya H, Matsumoto K, Nishida E, Hagiwara M | title = A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3 | journal = The Journal of Biological Chemistry | volume = 271 | issue = 23 | pages = 13675–9 | date = Jun 1996 | pmid = 8663074 | doi = 10.1074/jbc.271.23.13675 }}
*{{cite journal | author=Raingeaud J, Whitmarsh AJ, Barrett T, ''et al.'' |title=MKK3- and MKK6-regulated gene expression is mediated by the p38 mitogen-activated protein kinase signal transduction pathway. |journal=Mol. Cell. Biol. |volume=16 |issue= 3 |pages= 1247-55 |year= 1996 |pmid= 8622669 |doi= }}
* {{cite journal | vauthors = Cuenda A, Alonso G, Morrice N, Jones M, Meier R, Cohen P, Nebreda AR | title = Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress- and cytokine-stimulated monocytes and epithelial cells | journal = The EMBO Journal | volume = 15 | issue = 16 | pages = 4156–64 | date = Aug 1996 | pmid = 8861944 | pmc = 452138 | doi =  }}
*{{cite journal | author=Stein B, Brady H, Yang MX, ''et al.'' |title=Cloning and characterization of MEK6, a novel member of the mitogen-activated protein kinase kinase cascade. |journal=J. Biol. Chem. |volume=271 |issue= 19 |pages= 11427-33 |year= 1996 |pmid= 8626699 |doi= }}
* {{cite journal | vauthors = Goedert M, Cuenda A, Craxton M, Jakes R, Cohen P | title = 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 | journal = The EMBO Journal | volume = 16 | issue = 12 | pages = 3563–71 | date = Jun 1997 | pmid = 9218798 | pmc = 1169981 | doi = 10.1093/emboj/16.12.3563 }}
*{{cite journal | author=Moriguchi T, Kuroyanagi N, Yamaguchi K, ''et al.'' |title=A novel kinase cascade mediated by mitogen-activated protein kinase kinase 6 and MKK3. |journal=J. Biol. Chem. |volume=271 |issue= 23 |pages= 13675-9 |year= 1996 |pmid= 8663074 |doi=  }}
* {{cite journal | vauthors = Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, Suyama A, Sugano S | title = Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library | journal = Gene | volume = 200 | issue = 1-2 | pages = 149–56 | date = Oct 1997 | pmid = 9373149 | doi = 10.1016/S0378-1119(97)00411-3 }}
*{{cite journal | author=Cuenda A, Alonso G, Morrice N, ''et al.'' |title=Purification and cDNA cloning of SAPKK3, the major activator of RK/p38 in stress- and cytokine-stimulated monocytes and epithelial cells. |journal=EMBO J. |volume=15 |issue= 16 |pages= 4156-64 |year= 1996 |pmid= 8861944 |doi= }}
* {{cite journal | vauthors = Enslen H, Raingeaud J, Davis RJ | title = Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 3 | pages = 1741–8 | date = Jan 1998 | pmid = 9430721 | doi = 10.1074/jbc.273.3.1741 }}
*{{cite journal | author=Goedert M, Cuenda A, Craxton M, ''et al.'' |title=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. |journal=EMBO J. |volume=16 |issue= 12 |pages= 3563-71 |year= 1997 |pmid= 9218798 |doi= 10.1093/emboj/16.12.3563 }}
* {{cite journal | vauthors = Chan-Hui PY, Weaver R | title = Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase cascades | journal = The Biochemical Journal | volume = 336 | issue = Pt 3 | pages = 599–609 | date = Dec 1998 | pmid = 9841871 | pmc = 1219910 | doi =  10.1042/bj3360599}}
*{{cite journal | author=Suzuki Y, Yoshitomo-Nakagawa K, Maruyama K, ''et al.'' |title=Construction and characterization of a full length-enriched and a 5'-end-enriched cDNA library. |journal=Gene |volume=200 |issue= 1-2 |pages= 149-56 |year= 1997 |pmid= 9373149 |doi= }}
* {{cite journal | vauthors = Chen Z, Hutchison M, Cobb MH | title = Isolation of the protein kinase TAO2 and identification of its mitogen-activated protein kinase/extracellular signal-regulated kinase kinase binding domain | journal = The Journal of Biological Chemistry | volume = 274 | issue = 40 | pages = 28803–7 | date = Oct 1999 | pmid = 10497253 | doi = 10.1074/jbc.274.40.28803 }}
*{{cite journal | author=Enslen H, Raingeaud J, Davis RJ |title=Selective activation of p38 mitogen-activated protein (MAP) kinase isoforms by the MAP kinase kinases MKK3 and MKK6. |journal=J. Biol. Chem. |volume=273 |issue= 3 |pages= 1741-8 |year= 1998 |pmid= 9430721 |doi=  }}
* {{cite journal | vauthors = Cong F, Goff SP | title = c-Abl-induced apoptosis, but not cell cycle arrest, requires mitogen-activated protein kinase kinase 6 activation | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 24 | pages = 13819–24 | date = Nov 1999 | pmid = 10570156 | pmc = 24148 | doi = 10.1073/pnas.96.24.13819 }}
*{{cite journal | author=Chan-Hui PY, Weaver R |title=Human mitogen-activated protein kinase kinase kinase mediates the stress-induced activation of mitogen-activated protein kinase cascades. |journal=Biochem. J. |volume=336 ( Pt 3) |issue= |pages= 599-609 |year= 1999 |pmid= 9841871 |doi= }}
* {{cite journal | vauthors = Wang X, McGowan CH, Zhao M, He L, Downey JS, Fearns C, Wang Y, Huang S, Han J | title = Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest | journal = Molecular and Cellular Biology | volume = 20 | issue = 13 | pages = 4543–52 | date = Jul 2000 | pmid = 10848581 | pmc = 85840 | doi = 10.1128/MCB.20.13.4543-4552.2000 }}
*{{cite journal | author=Chen Z, Hutchison M, Cobb MH |title=Isolation of the protein kinase TAO2 and identification of its mitogen-activated protein kinase/extracellular signal-regulated kinase kinase binding domain. |journal=J. Biol. Chem. |volume=274 |issue= 40 |pages= 28803-7 |year= 1999 |pmid= 10497253 |doi= }}
* {{cite journal | vauthors = Visconti R, Gadina M, Chiariello M, Chen EH, Stancato LF, Gutkind JS, O'Shea JJ | title = Importance of the MKK6/p38 pathway for interleukin-12-induced STAT4 serine phosphorylation and transcriptional activity | journal = Blood | volume = 96 | issue = 5 | pages = 1844–52 | date = Sep 2000 | pmid = 10961885 | doi =  }}
*{{cite journal | author=Cong F, Goff SP |title=c-Abl-induced apoptosis, but not cell cycle arrest, requires mitogen-activated protein kinase kinase 6 activation. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue= 24 |pages= 13819-24 |year= 2000 |pmid= 10570156 |doi= }}
* {{cite journal | vauthors = Fleming Y, Armstrong CG, Morrice N, Paterson A, Goedert M, Cohen P | title = 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 | journal = The Biochemical Journal | volume = 352 Pt 1 | issue = Pt 1 | pages = 145–54 | date = Nov 2000 | pmid = 11062067 | pmc = 1221441 | doi = 10.1042/0264-6021:3520145 }}
*{{cite journal | author=Wang X, McGowan CH, Zhao M, ''et al.'' |title=Involvement of the MKK6-p38gamma cascade in gamma-radiation-induced cell cycle arrest. |journal=Mol. Cell. Biol. |volume=20 |issue= 13 |pages= 4543-52 |year= 2000 |pmid= 10848581 |doi=  }}
* {{cite journal | vauthors = Vitale G, Bernardi L, Napolitani G, Mock M, Montecucco C | title = Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor | journal = The Biochemical Journal | volume = 352 Pt 3 | issue = Pt 3 | pages = 739–45 | date = Dec 2000 | pmid = 11104681 | pmc = 1221512 | doi = 10.1042/0264-6021:3520739 }}
*{{cite journal | author=Visconti R, Gadina M, Chiariello M, ''et al.'' |title=Importance of the MKK6/p38 pathway for interleukin-12-induced STAT4 serine phosphorylation and transcriptional activity. |journal=Blood |volume=96 |issue= 5 |pages= 1844-52 |year= 2000 |pmid= 10961885 |doi= }}
*{{cite journal | author=Fleming Y, Armstrong CG, Morrice N, ''et al.'' |title=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. |journal=Biochem. J. |volume=352 Pt 1 |issue= |pages= 145-54 |year= 2001 |pmid= 11062067 |doi= }}
*{{cite journal  | author=Vitale G, Bernardi L, Napolitani G, ''et al.'' |title=Susceptibility of mitogen-activated protein kinase kinase family members to proteolysis by anthrax lethal factor. |journal=Biochem. J. |volume=352 Pt 3 |issue=  |pages= 739-45 |year= 2001 |pmid= 11104681 |doi=  }}
}}
{{refend}}
{{refend}}


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Latest revision as of 06:05, 4 September 2017

Main article: Mitogen-activated protein kinase kinase
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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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UniProt

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RefSeq (mRNA)

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RefSeq (protein)

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View/Edit Human

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]

Function

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]

Interactions

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

References

  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. ↑ 3.0 3.1 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. doi:10.1128/mcb.16.3.1247. 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

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