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{{Infobox_gene}}
{{PBB_Controls
'''Mitogen-activated protein kinase kinase kinase 1''' is an [[enzyme]] that in humans is encoded by the ''MAP3K1'' [[gene]].<ref name="pmid8597633">{{cite journal | vauthors = Vinik BS, Kay ES, Fiedorek FT | title = Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human chromosome 5 | journal = Mammalian Genome | volume = 6 | issue = 11 | pages = 782–3 | date = November 1995 | pmid = 8597633 | pmc =  | doi = 10.1007/BF00539003 }}</ref><ref name="entrez">{{cite web | title = Entrez Gene: MAP3K1 mitogen-activated protein kinase kinase kinase 1| url = https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4214| access-date = }}</ref>
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== Function ==
| update_protein_box = yes
 
| update_summary = yes
MAP3K, or MEK kinase or Raf, is a serine/threonine kinase that occupies a pivotal role in a network of phosphorylating enzymes integrating cellular responses to a number of mitogenic and metabolic stimuli, including [[insulin]] and many growth factors.<ref name="entrez"/>
| update_citations = yes
 
}}
Mouse genetics has revealed that the kinase is important in: correct embryogenesis, keratinocyte migration, T cell cytokine production and B cell antibody production.
 
''MAP3K1'' is a regulatory target of [[Genome-wide association study|GWAS]] variants associated with breast cancer risk <ref name = "Glubb_2015" />
 
== Interactions ==
 
MAP3K1 has been shown to [[Protein-protein interaction|interact]] with:
* [[AXIN1]],<ref name = pmid11884395>{{cite journal | vauthors = Zhang Y, Qiu WJ, Chan SC, Han J, He X, Lin SC | title = Casein kinase I and casein kinase II differentially regulate axin function in Wnt and JNK pathways | journal = The Journal of Biological Chemistry | volume = 277 | issue = 20 | pages = 17706–12 | date = May 2002 | pmid = 11884395 | doi = 10.1074/jbc.M111982200 }}</ref><ref name = pmid10829020>{{cite journal | vauthors = Zhang Y, Neo SY, Han J, Lin SC | title = Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase | journal = The Journal of Biological Chemistry | volume = 275 | issue = 32 | pages = 25008–14 | date = August 2000 | pmid = 10829020 | doi = 10.1074/jbc.M002491200 }}</ref>  
* [[C-Raf]],<ref name = pmid10969079>{{cite journal | vauthors = Karandikar M, Xu S, Cobb MH | title = MEKK1 binds raf-1 and the ERK2 cascade components | journal = The Journal of Biological Chemistry | volume = 275 | issue = 51 | pages = 40120–7 | date = December 2000 | pmid = 10969079 | doi = 10.1074/jbc.M005926200 }}</ref>
* [[Grb2]],<ref name = pmid9733714>{{cite journal | vauthors = Pomérance M, Multon MC, Parker F, Venot C, Blondeau JP, Tocqué B, Schweighoffer F | title = Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun-kinase activities in response to epidermal growth factor | journal = The Journal of Biological Chemistry | volume = 273 | issue = 38 | pages = 24301–4 | date = September 1998 | pmid = 9733714 | doi = 10.1074/jbc.273.38.24301 }}</ref>
* [[MAP2K1]],<ref name = pmid10969079/>
* [[MAPK1]],<ref name = pmid10969079/>
* [[MAPK8]],<ref name = pmid9405400>{{cite journal | vauthors = Xu S, Cobb MH | title = MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases | journal = The Journal of Biological Chemistry | volume = 272 | issue = 51 | pages = 32056–60 | date = December 1997 | pmid = 9405400 | doi = 10.1074/jbc.272.51.32056 }}</ref>
* [[TRAF2]],<ref name = pmid10346818>{{cite journal | vauthors = Baud V, Liu ZG, Bennett B, Suzuki N, Xia Y, Karin M | title = Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain | journal = Genes & Development | volume = 13 | issue = 10 | pages = 1297–308 | date = May 1999 | pmid = 10346818 | pmc = 316725 | doi = 10.1101/gad.13.10.1297 }}</ref>  and
* [[UBE2I]].<ref name = pmid9563508>{{cite journal | vauthors = Saltzman A, Searfoss G, Marcireau C, Stone M, Ressner R, Munro R, Franks C, D'Alonzo J, Tocque B, Jaye M, Ivashchenko Y | title = hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity | journal = FEBS Letters | volume = 425 | issue = 3 | pages = 431–5 | date = April 1998 | pmid = 9563508 | doi = 10.1016/s0014-5793(98)00287-7 }}</ref>
{{clear}}


<!-- The GNF_Protein_box is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
== References ==
{{GNF_Protein_box
{{reflist|32em| refs = <ref name = "Glubb_2015">{{cite journal | vauthors = Glubb DM, Maranian MJ, Michailidou K, Pooley KA, Meyer KB, Kar S, Carlebur S, O'Reilly M, Betts JA, Hillman KM, Kaufmann S, Beesley J, Canisius S, Hopper JL, Southey MC, Tsimiklis H, Apicella C, Schmidt MK, Broeks A, Hogervorst FB, van der Schoot CE, Muir K, Lophatananon A, Stewart-Brown S, Siriwanarangsan P, Fasching PA, Ruebner M, Ekici AB, Beckmann MW, Peto J, dos-Santos-Silva I, Fletcher O, Johnson N, Pharoah PD, Bolla MK, Wang Q, Dennis J, Sawyer EJ, Tomlinson I, Kerin MJ, Miller N, Burwinkel B, Marme F, Yang R, Surowy H, Guénel P, Truong T, Menegaux F, Sanchez M, Bojesen SE, Nordestgaard BG, Nielsen SF, Flyger H, González-Neira A, Benitez J, Zamora MP, Arias Perez JI, Anton-Culver H, Neuhausen SL, Brenner H, Dieffenbach AK, Arndt V, Stegmaier C, Meindl A, Schmutzler RK, Brauch H, Ko YD, Brüning T, Nevanlinna H, Muranen TA, Aittomäki K, Blomqvist C, Matsuo K, Ito H, Iwata H, Tanaka H, Dörk T, Bogdanova NV, Helbig S, Lindblom A, Margolin S, Mannermaa A, Kataja V, Kosma VM, Hartikainen JM, Wu AH, Tseng CC, Van Den Berg D, Stram DO, Lambrechts D, Zhao H, Weltens C, van Limbergen E, Chang-Claude J, Flesch-Janys D, Rudolph A, Seibold P, Radice P, Peterlongo P, Barile M, Capra F, Couch FJ, Olson JE, Hallberg E, Vachon C, Giles GG, Milne RL, McLean C, Haiman CA, Henderson BE, Schumacher F, Le Marchand L, Simard J, Goldberg MS, Labrèche F, Dumont M, Teo SH, Yip CH, See MH, Cornes B, Cheng CY, Ikram MK, Kristensen V, Zheng W, Halverson SL, Shrubsole M, Long J, Winqvist R, Pylkäs K, Jukkola-Vuorinen A, Kauppila S, Andrulis IL, Knight JA, Glendon G, Tchatchou S, Devilee P, Tollenaar RA, Seynaeve C, Van Asperen CJ, García-Closas M, Figueroa J, Chanock SJ, Lissowska J, Czene K, Klevebring D, Darabi H, Eriksson M, Hooning MJ, Hollestelle A, Martens JW, Collée JM, Hall P, Li J, Humphreys K, Shu XO, Lu W, Gao YT, Cai H, Cox A, Cross SS, Reed MW, Blot W, Signorello LB, Cai Q, Shah M, Ghoussaini M, Kang D, Choi JY, Park SK, Noh DY, Hartman M, Miao H, Lim WY, Tang A, Hamann U, Torres D, Jakubowska A, Lubinski J, Jaworska K, Durda K, Sangrajrang S, Gaborieau V, Brennan P, McKay J, Olswold C, Slager S, Toland AE, Yannoukakos D, Shen CY, Wu PE, Yu JC, Hou MF, Swerdlow A, Ashworth A, Orr N, Jones M, Pita G, Alonso MR, Álvarez N, Herrero D, Tessier DC, Vincent D, Bacot F, Luccarini C, Baynes C, Ahmed S, Healey CS, Brown MA, Ponder BA, Chenevix-Trench G, Thompson DJ, Edwards SL, Easton DF, Dunning AM, French JD | display-authors = 6 | title = Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1 | journal = American Journal of Human Genetics | volume = 96 | issue = 1 | pages = 5–20 | date = January 2015 | pmid = 25529635 | pmc = 4289692 | doi = 10.1016/j.ajhg.2014.11.009 }}</ref>
| image = 
| image_source = 
| PDB =
| Name = Mitogen-activated protein kinase kinase kinase 1
| HGNCid = 6848
| Symbol = MAP3K1
| AltSymbols =; MAPKKK1; MEKK; MEKK1
| OMIM = 600982
| ECnumber = 
| Homologene = 8056
| MGIid = 1346872
| GeneAtlas_image1 = PBB_GE_MAP3K1_214786_at_tn.png
| Function = {{GNF_GO|id=GO:0000166 |text = nucleotide binding}} {{GNF_GO|id=GO:0000287 |text = magnesium ion binding}} {{GNF_GO|id=GO:0004674 |text = protein serine/threonine kinase activity}} {{GNF_GO|id=GO:0004709 |text = MAP kinase kinase kinase activity}} {{GNF_GO|id=GO:0005515 |text = protein binding}} {{GNF_GO|id=GO:0005524 |text = ATP binding}} {{GNF_GO|id=GO:0008270 |text = zinc ion binding}} {{GNF_GO|id=GO:0016740 |text = transferase activity}}
| Component = {{GNF_GO|id=GO:0005575 |text = cellular_component}}
| Process = {{GNF_GO|id=GO:0006468 |text = protein amino acid phosphorylation}} {{GNF_GO|id=GO:0007179 |text = transforming growth factor beta receptor signaling pathway}} {{GNF_GO|id=GO:0008637 |text = apoptotic mitochondrial changes}} {{GNF_GO|id=GO:0030334 |text = regulation of cell migration}} {{GNF_GO|id=GO:0030838 |text = positive regulation of actin filament polymerization}} {{GNF_GO|id=GO:0042060 |text = wound healing}}
| Orthologs = {{GNF_Ortholog_box
    | Hs_EntrezGene = 4214
    | Hs_Ensembl = ENSG00000095015
    | Hs_RefseqProtein = XP_001128827
    | Hs_RefseqmRNA = XM_001128827
    | Hs_GenLoc_db =
    | Hs_GenLoc_chr = 5
    | Hs_GenLoc_start = 56147216
    | Hs_GenLoc_end = 56225472
    | Hs_Uniprot = Q13233
    | Mm_EntrezGene = 26401
    | Mm_Ensembl = 
    | Mm_RefseqmRNA = NM_011945
    | Mm_RefseqProtein = NP_036075
    | Mm_GenLoc_db = 
    | Mm_GenLoc_chr = 
    | Mm_GenLoc_start = 
    | Mm_GenLoc_end = 
    | Mm_Uniprot = 
  }}
}}
'''Mitogen-activated protein kinase kinase kinase 1''', also known as '''MAP3K1''', is a human [[gene]].<ref name="entrez">{{cite web | title = Entrez Gene: MAP3K1 mitogen-activated protein kinase kinase kinase 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4214| accessdate = }}</ref>


<!-- The PBB_Summary template is automatically maintained by Protein Box Bot.  See Template:PBB_Controls to Stop updates. -->
{{PBB_Summary
| section_title =
| summary_text = MAP3K, or MEK kinase, is a serine/threonine kinase that occupies a pivotal role in a network of phosphorylating enzymes integrating cellular responses to a number of mitogenic and metabolic stimuli, including insulin (MIM 176730) and many growth factors.[supplied by OMIM]<ref name="entrez">{{cite web | title = Entrez Gene: MAP3K1 mitogen-activated protein kinase kinase kinase 1| url = http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=4214| accessdate = }}</ref>
}}
}}


==References==
== Further reading ==
{{reflist|2}}
{{refbegin|32em}}
==Further reading==
* {{cite journal | vauthors = Lee FS, Hagler J, Chen ZJ, Maniatis T | title = Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway | journal = Cell | volume = 88 | issue = 2 | pages = 213–22 | date = January 1997 | pmid = 9008162 | doi = 10.1016/S0092-8674(00)81842-5 }}
{{refbegin | 2}}
* {{cite journal | vauthors = Siow YL, Kalmar GB, Sanghera JS, Tai G, Oh SS, Pelech SL | title = Identification of two essential phosphorylated threonine residues in the catalytic domain of Mekk1. Indirect activation by Pak3 and protein kinase C | journal = The Journal of Biological Chemistry | volume = 272 | issue = 12 | pages = 7586–94 | date = March 1997 | pmid = 9065412 | doi = 10.1074/jbc.272.12.7586 }}
{{PBB_Further_reading
* {{cite journal | vauthors = Su YC, Han J, Xu S, Cobb M, Skolnik EY | title = NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain | journal = The EMBO Journal | volume = 16 | issue = 6 | pages = 1279–90 | date = March 1997 | pmid = 9135144 | pmc = 1169726 | doi = 10.1093/emboj/16.6.1279 }}
| citations =
* {{cite journal | vauthors = Wu Z, Wu J, Jacinto E, Karin M | title = Molecular cloning and characterization of human JNKK2, a novel Jun NH2-terminal kinase-specific kinase | journal = Molecular and Cellular Biology | volume = 17 | issue = 12 | pages = 7407–16 | date = December 1997 | pmid = 9372971 | pmc = 232596 | doi = 10.1128/mcb.17.12.7407 }}
*{{cite journal | author=Vinik BS, Kay ES, Fiedorek FT |title=Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human chromosome 5. |journal=Mamm. Genome |volume=6 |issue= 11 |pages= 782-3 |year= 1996 |pmid= 8597633 |doi= }}
* {{cite journal | vauthors = Xu S, Cobb MH | title = MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases | journal = The Journal of Biological Chemistry | volume = 272 | issue = 51 | pages = 32056–60 | date = December 1997 | pmid = 9405400 | doi = 10.1074/jbc.272.51.32056 }}
*{{cite journal | author=Lee FS, Hagler J, Chen ZJ, Maniatis T |title=Activation of the IkappaB alpha kinase complex by MEKK1, a kinase of the JNK pathway. |journal=Cell |volume=88 |issue= 2 |pages= 213-22 |year= 1997 |pmid= 9008162 |doi= }}
* {{cite journal | vauthors = Fanger GR, Widmann C, Porter AC, Sather S, Johnson GL, Vaillancourt RR | title = 14-3-3 proteins interact with specific MEK kinases | journal = The Journal of Biological Chemistry | volume = 273 | issue = 6 | pages = 3476–83 | date = February 1998 | pmid = 9452471 | doi = 10.1074/jbc.273.6.3476 }}
*{{cite journal | author=Siow YL, Kalmar GB, Sanghera JS, ''et al.'' |title=Identification of two essential phosphorylated threonine residues in the catalytic domain of Mekk1. Indirect activation by Pak3 and protein kinase C. |journal=J. Biol. Chem. |volume=272 |issue= 12 |pages= 7586-94 |year= 1997 |pmid= 9065412 |doi= }}
* {{cite journal | vauthors = Hirai S, Noda K, Moriguchi T, Nishida E, Yamashita A, Deyama T, Fukuyama K, Ohno S | title = Differential activation of two JNK activators, MKK7 and SEK1, by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 13 | pages = 7406–12 | date = March 1998 | pmid = 9516438 | doi = 10.1074/jbc.273.13.7406 }}
*{{cite journal | author=Su YC, Han J, Xu S, ''et al.'' |title=NIK is a new Ste20-related kinase that binds NCK and MEKK1 and activates the SAPK/JNK cascade via a conserved regulatory domain. |journal=EMBO J. |volume=16 |issue= 6 |pages= 1279-90 |year= 1997 |pmid= 9135144 |doi= 10.1093/emboj/16.6.1279 }}
* {{cite journal | vauthors = Saltzman A, Searfoss G, Marcireau C, Stone M, Ressner R, Munro R, Franks C, D'Alonzo J, Tocque B, Jaye M, Ivashchenko Y | title = hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity | journal = FEBS Letters | volume = 425 | issue = 3 | pages = 431–5 | date = April 1998 | pmid = 9563508 | doi = 10.1016/S0014-5793(98)00287-7 }}
*{{cite journal | author=Wu Z, Wu J, Jacinto E, Karin M |title=Molecular cloning and characterization of human JNKK2, a novel Jun NH2-terminal kinase-specific kinase. |journal=Mol. Cell. Biol. |volume=17 |issue= 12 |pages= 7407-16 |year= 1997 |pmid= 9372971 |doi= }}
* {{cite journal | vauthors = Guan Z, Buckman SY, Pentland AP, Templeton DJ, Morrison AR | title = Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway | journal = The Journal of Biological Chemistry | volume = 273 | issue = 21 | pages = 12901–8 | date = May 1998 | pmid = 9582321 | doi = 10.1074/jbc.273.21.12901 }}
*{{cite journal | author=Xu S, Cobb MH |title=MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases. |journal=J. Biol. Chem. |volume=272 |issue= 51 |pages= 32056-60 |year= 1998 |pmid= 9405400 |doi= }}
* {{cite journal | vauthors = Lee FS, Peters RT, Dang LC, Maniatis T | title = MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 95 | issue = 16 | pages = 9319–24 | date = August 1998 | pmid = 9689078 | pmc = 21336 | doi = 10.1073/pnas.95.16.9319 }}
*{{cite journal | author=Fanger GR, Widmann C, Porter AC, ''et al.'' |title=14-3-3 proteins interact with specific MEK kinases. |journal=J. Biol. Chem. |volume=273 |issue= 6 |pages= 3476-83 |year= 1998 |pmid= 9452471 |doi= }}
* {{cite journal | vauthors = Yuasa T, Ohno S, Kehrl JH, Kyriakis JM | title = Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38 | journal = The Journal of Biological Chemistry | volume = 273 | issue = 35 | pages = 22681–92 | date = August 1998 | pmid = 9712898 | doi = 10.1074/jbc.273.35.22681 }}
*{{cite journal | author=Hirai S, Noda K, Moriguchi T, ''et al.'' |title=Differential activation of two JNK activators, MKK7 and SEK1, by MKN28-derived nonreceptor serine/threonine kinase/mixed lineage kinase 2. |journal=J. Biol. Chem. |volume=273 |issue= 13 |pages= 7406-12 |year= 1998 |pmid= 9516438 |doi= }}
* {{cite journal | vauthors = Pomérance M, Multon MC, Parker F, Venot C, Blondeau JP, Tocqué B, Schweighoffer F | title = Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun-kinase activities in response to epidermal growth factor | journal = The Journal of Biological Chemistry | volume = 273 | issue = 38 | pages = 24301–4 | date = September 1998 | pmid = 9733714 | doi = 10.1074/jbc.273.38.24301 }}
*{{cite journal | author=Saltzman A, Searfoss G, Marcireau C, ''et al.'' |title=hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity. |journal=FEBS Lett. |volume=425 |issue= 3 |pages= 431-5 |year= 1998 |pmid= 9563508 |doi= }}
* {{cite journal | vauthors = Xia Y, Wu Z, Su B, Murray B, Karin M | title = JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension | journal = Genes & Development | volume = 12 | issue = 21 | pages = 3369–81 | date = November 1998 | pmid = 9808624 | pmc = 317229 | doi = 10.1101/gad.12.21.3369 }}
*{{cite journal | author=Guan Z, Buckman SY, Pentland AP, ''et al.'' |title=Induction of cyclooxygenase-2 by the activated MEKK1 --> SEK1/MKK4 --> p38 mitogen-activated protein kinase pathway. |journal=J. Biol. Chem. |volume=273 |issue= 21 |pages= 12901-8 |year= 1998 |pmid= 9582321 |doi= }}
* {{cite journal | vauthors = Nemoto S, DiDonato JA, Lin A | title = Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase | journal = Molecular and Cellular Biology | volume = 18 | issue = 12 | pages = 7336–43 | date = December 1998 | pmid = 9819420 | pmc = 109315 | doi = 10.1128/mcb.18.12.7336 }}
*{{cite journal | author=Lee FS, Peters RT, Dang LC, Maniatis T |title=MEKK1 activates both IkappaB kinase alpha and IkappaB kinase beta. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=95 |issue= 16 |pages= 9319-24 |year= 1998 |pmid= 9689078 |doi= }}
* {{cite journal | vauthors = Yujiri T, Sather S, Fanger GR, Johnson GL | title = Role of MEKK1 in cell survival and activation of JNK and ERK pathways defined by targeted gene disruption | journal = Science | volume = 282 | issue = 5395 | pages = 1911–4 | date = December 1998 | pmid = 9836645 | doi = 10.1126/science.282.5395.1911 }}
*{{cite journal | author=Yuasa T, Ohno S, Kehrl JH, Kyriakis JM |title=Tumor necrosis factor signaling to stress-activated protein kinase (SAPK)/Jun NH2-terminal kinase (JNK) and p38. Germinal center kinase couples TRAF2 to mitogen-activated protein kinase/ERK kinase kinase 1 and SAPK while receptor interacting protein associates with a mitogen-activated protein kinase kinase kinase upstream of MKK6 and p38. |journal=J. Biol. Chem. |volume=273 |issue= 35 |pages= 22681-92 |year= 1998 |pmid= 9712898 |doi= }}
* {{cite journal | vauthors = Baud V, Liu ZG, Bennett B, Suzuki N, Xia Y, Karin M | title = Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain | journal = Genes & Development | volume = 13 | issue = 10 | pages = 1297–308 | date = May 1999 | pmid = 10346818 | pmc = 316725 | doi = 10.1101/gad.13.10.1297 }}
*{{cite journal | author=Pomérance M, Multon MC, Parker F, ''et al.'' |title=Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun-kinase activities in response to epidermal growth factor. |journal=J. Biol. Chem. |volume=273 |issue= 38 |pages= 24301-4 |year= 1998 |pmid= 9733714 |doi= }}
* {{cite journal | vauthors = Kopp E, Medzhitov R, Carothers J, Xiao C, Douglas I, Janeway CA, Ghosh S | title = ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway | journal = Genes & Development | volume = 13 | issue = 16 | pages = 2059–71 | date = August 1999 | pmid = 10465784 | pmc = 316957 | doi = 10.1101/gad.13.16.2059 }}
*{{cite journal | author=Xia Y, Wu Z, Su B, ''et al.'' |title=JNKK1 organizes a MAP kinase module through specific and sequential interactions with upstream and downstream components mediated by its amino-terminal extension. |journal=Genes Dev. |volume=12 |issue= 21 |pages= 3369-81 |year= 1998 |pmid= 9808624 |doi= }}
* {{cite journal | vauthors = Ito M, Yoshioka K, Akechi M, Yamashita S, Takamatsu N, Sugiyama K, Hibi M, Nakabeppu Y, Shiba T, Yamamoto KI | title = JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway | journal = Molecular and Cellular Biology | volume = 19 | issue = 11 | pages = 7539–48 | date = November 1999 | pmid = 10523642 | pmc = 84763 | doi = 10.1128/mcb.19.11.7539 }}
*{{cite journal | author=Nemoto S, DiDonato JA, Lin A |title=Coordinate regulation of IkappaB kinases by mitogen-activated protein kinase kinase kinase 1 and NF-kappaB-inducing kinase. |journal=Mol. Cell. Biol. |volume=18 |issue= 12 |pages= 7336-43 |year= 1998 |pmid= 9819420 |doi= }}
* {{cite journal | vauthors = Minamino T, Yujiri T, Papst PJ, Chan ED, Johnson GL, Terada N | title = MEKK1 suppresses oxidative stress-induced apoptosis of embryonic stem cell-derived cardiac myocytes | journal = Proceedings of the National Academy of Sciences of the United States of America | volume = 96 | issue = 26 | pages = 15127–32 | date = December 1999 | pmid = 10611349 | pmc = 24784 | doi = 10.1073/pnas.96.26.15127 }}
*{{cite journal | author=Yujiri T, Sather S, Fanger GR, Johnson GL |title=Role of MEKK1 in cell survival and activation of JNK and ERK pathways defined by targeted gene disruption. |journal=Science |volume=282 |issue= 5395 |pages= 1911-4 |year= 1998 |pmid= 9836645 |doi= }}
*{{cite journal | author=Baud V, Liu ZG, Bennett B, ''et al.'' |title=Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain. |journal=Genes Dev. |volume=13 |issue= 10 |pages= 1297-308 |year= 1999 |pmid= 10346818 |doi= }}
*{{cite journal | author=Kopp E, Medzhitov R, Carothers J, ''et al.'' |title=ECSIT is an evolutionarily conserved intermediate in the Toll/IL-1 signal transduction pathway. |journal=Genes Dev. |volume=13 |issue= 16 |pages= 2059-71 |year= 1999 |pmid= 10465784 |doi= }}
*{{cite journal | author=Ito M, Yoshioka K, Akechi M, ''et al.'' |title=JSAP1, a novel jun N-terminal protein kinase (JNK)-binding protein that functions as a Scaffold factor in the JNK signaling pathway. |journal=Mol. Cell. Biol. |volume=19 |issue= 11 |pages= 7539-48 |year= 1999 |pmid= 10523642 |doi= }}
*{{cite journal  | author=Minamino T, Yujiri T, Papst PJ, ''et al.'' |title=MEKK1 suppresses oxidative stress-induced apoptosis of embryonic stem cell-derived cardiac myocytes. |journal=Proc. Natl. Acad. Sci. U.S.A. |volume=96 |issue= 26 |pages= 15127-32 |year= 2000 |pmid= 10611349 |doi=  }}
}}
{{refend}}
{{refend}}


{{protein-stub}}
{{Serine/threonine-specific protein kinases}}
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[[Category:Mitogen-activated Protein Kinases]]
[[Category:EC 2.7.11]]

Latest revision as of 06:12, 24 October 2018

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Identifiers
Aliases
External IDsGeneCards: [1]
Orthologs
SpeciesHumanMouse
Entrez

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Ensembl

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Mitogen-activated protein kinase kinase kinase 1 is an enzyme that in humans is encoded by the MAP3K1 gene.[1][2]

Function

MAP3K, or MEK kinase or Raf, is a serine/threonine kinase that occupies a pivotal role in a network of phosphorylating enzymes integrating cellular responses to a number of mitogenic and metabolic stimuli, including insulin and many growth factors.[2]

Mouse genetics has revealed that the kinase is important in: correct embryogenesis, keratinocyte migration, T cell cytokine production and B cell antibody production.

MAP3K1 is a regulatory target of GWAS variants associated with breast cancer risk [3]

Interactions

MAP3K1 has been shown to interact with:

References

  1. ↑ Vinik BS, Kay ES, Fiedorek FT (November 1995). "Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human chromosome 5". Mammalian Genome. 6 (11): 782–3. doi:10.1007/BF00539003. PMID 8597633.
  2. ↑ 2.0 2.1 "Entrez Gene: MAP3K1 mitogen-activated protein kinase kinase kinase 1".
  3. ↑ Glubb DM, Maranian MJ, Michailidou K, Pooley KA, Meyer KB, Kar S, et al. (January 2015). "Fine-scale mapping of the 5q11.2 breast cancer locus reveals at least three independent risk variants regulating MAP3K1". American Journal of Human Genetics. 96 (1): 5–20. doi:10.1016/j.ajhg.2014.11.009. PMC 4289692. PMID 25529635.
  4. ↑ Zhang Y, Qiu WJ, Chan SC, Han J, He X, Lin SC (May 2002). "Casein kinase I and casein kinase II differentially regulate axin function in Wnt and JNK pathways". The Journal of Biological Chemistry. 277 (20): 17706–12. doi:10.1074/jbc.M111982200. PMID 11884395.
  5. ↑ Zhang Y, Neo SY, Han J, Lin SC (August 2000). "Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase". The Journal of Biological Chemistry. 275 (32): 25008–14. doi:10.1074/jbc.M002491200. PMID 10829020.
  6. ↑ 6.0 6.1 6.2 Karandikar M, Xu S, Cobb MH (December 2000). "MEKK1 binds raf-1 and the ERK2 cascade components". The Journal of Biological Chemistry. 275 (51): 40120–7. doi:10.1074/jbc.M005926200. PMID 10969079.
  7. ↑ Pomérance M, Multon MC, Parker F, Venot C, Blondeau JP, Tocqué B, Schweighoffer F (September 1998). "Grb2 interaction with MEK-kinase 1 is involved in regulation of Jun-kinase activities in response to epidermal growth factor". The Journal of Biological Chemistry. 273 (38): 24301–4. doi:10.1074/jbc.273.38.24301. PMID 9733714.
  8. ↑ Xu S, Cobb MH (December 1997). "MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases". The Journal of Biological Chemistry. 272 (51): 32056–60. doi:10.1074/jbc.272.51.32056. PMID 9405400.
  9. ↑ Baud V, Liu ZG, Bennett B, Suzuki N, Xia Y, Karin M (May 1999). "Signaling by proinflammatory cytokines: oligomerization of TRAF2 and TRAF6 is sufficient for JNK and IKK activation and target gene induction via an amino-terminal effector domain". Genes & Development. 13 (10): 1297–308. doi:10.1101/gad.13.10.1297. PMC 316725. PMID 10346818.
  10. ↑ Saltzman A, Searfoss G, Marcireau C, Stone M, Ressner R, Munro R, Franks C, D'Alonzo J, Tocque B, Jaye M, Ivashchenko Y (April 1998). "hUBC9 associates with MEKK1 and type I TNF-alpha receptor and stimulates NFkappaB activity". FEBS Letters. 425 (3): 431–5. doi:10.1016/s0014-5793(98)00287-7. PMID 9563508.

Further reading

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