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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2013/05/04 19:41:03」(JST)

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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]

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]^[2]

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

Interactions

MAP3K1 has been shown to interact with C-Raf,^[3] MAPK8,^[4] TRAF2,^[5] MAP2K1,^[3] Grb2,^[6] MAPK1,^[3] AXIN1^[7]^[8] and UBE2I.^[9]

References

^ Vinik BS, Kay ES, Fiedorek FT Jr (April 1996). "Mapping of the MEK kinase gene (Mekk) to mouse chromosome 13 and human chromosome 5". Mamm Genome 6 (11): 782–3. doi:10.1007/BF00539003. PMID 8597633.
^ ^a ^b "Entrez Gene: MAP3K1 mitogen-activated protein kinase kinase kinase 1".
^ ^a ^b ^c Karandikar, M; Xu S, Cobb M H (December 2000). "MEKK1 binds raf-1 and the ERK2 cascade components". J. Biol. Chem. (UNITED STATES) 275 (51): 40120–7. doi:10.1074/jbc.M005926200. ISSN 0021-9258. PMID 10969079.
^ Xu, S; Cobb M H (December 1997). "MEKK1 binds directly to the c-Jun N-terminal kinases/stress-activated protein kinases". J. Biol. Chem. (UNITED STATES) 272 (51): 32056–60. doi:10.1074/jbc.272.51.32056. ISSN 0021-9258. PMID 9405400.
^ Baud, V; Liu Z G, 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 Dev. (UNITED STATES) 13 (10): 1297–308. doi:10.1101/gad.13.10.1297. ISSN 0890-9369. PMC 316725. PMID 10346818.
^ Pomérance, M; Multon M C, Parker F, Venot C, Blondeau J P, 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". J. Biol. Chem. (UNITED STATES) 273 (38): 24301–4. doi:10.1074/jbc.273.38.24301. ISSN 0021-9258. PMID 9733714.
^ Zhang, Yi; Qiu Wen-Jie, Chan Siu Chiu, Han Jiahuai, He Xi, Lin Sheng-Cai (May. 2002). "Casein kinase I and casein kinase II differentially regulate axin function in Wnt and JNK pathways". J. Biol. Chem. (United States) 277 (20): 17706–12. doi:10.1074/jbc.M111982200. ISSN 0021-9258. PMID 11884395.
^ Zhang, Y; Neo S Y, Han J, Lin S C (August 2000). "Dimerization choices control the ability of axin and dishevelled to activate c-Jun N-terminal kinase/stress-activated protein kinase". J. Biol. Chem. (UNITED STATES) 275 (32): 25008–14. doi:10.1074/jbc.M002491200. ISSN 0021-9258. PMID 10829020.
^ 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 Lett. (NETHERLANDS) 425 (3): 431–5. doi:10.1016/S0014-5793(98)00287-7. ISSN 0014-5793. PMID 9563508.

English Journal

MAP2K1 and MAP3K1 mutations in langerhans cell histiocytosis.

Nelson DS1, van Halteren A, Quispel WT, van den Bos C, Bovée JV, Patel B, Badalian-Very G, van Hummelen P, Ducar M, Lin L, MacConaill LE, Egeler RM, Rollins BJ.
Genes, chromosomes & cancer.Genes Chromosomes Cancer.2015 Jun;54(6):361-8. doi: 10.1002/gcc.22247. Epub 2015 Mar 31.
Langerhans cell histiocytosis (LCH) is now understood to be a neoplastic disease in which over 50% of cases have somatic activating mutations of BRAF. However, the extracellular signal-related (ERK) pathway is activated in all cases including those with wild type BRAF alleles. Here, we applied a tar
PMID 25899310

Nuclear localization signal and p53 binding site in MAP/ERK kinase kinase 1 (MEKK1).

Chipps E1, Protzman A1, Muhi MZ1, Ando S1, Calvet JP2, Islam MR1.
Journal of cellular biochemistry.J Cell Biochem.2015 May 27. doi: 10.1002/jcb.25238. [Epub ahead of print]
Previously, we showed that Mekk1 translocates to the nucleus, interacts with tumor suppressor protein p53 and co-represses PKD1 transcription via an atypical p53 binding site on the minimal PKD1 promoter (JBC 285:38818-38831, 2010). In this study, we report the mechanisms of Mekk1 nuclear transport
PMID 26018553

Oncolytic reovirus induces intracellular redistribution of Ras to promote apoptosis and progeny virus release.

Garant KA1, Shmulevitz M2, Pan L3, Daigle RM4, Ahn DG1, Gujar SA5, Lee PW6.
Oncogene.Oncogene.2015 May 11. doi: 10.1038/onc.2015.136. [Epub ahead of print]
Reovirus is a naturally oncolytic virus that preferentially replicates in Ras-transformed cells and is currently undergoing clinical trials as a cancer therapeutic. Ras transformation promotes reovirus oncolysis by enhancing virion disassembly during entry, viral progeny production, and virus releas
PMID 25961930

Japanese Journal

The Role of MEKK1 in Hypertrophic Cardiomyopathy

Konhilas John P.,Boucek Dana M.,Horn Todd R.,Johnson Gary L.,Leinwand Leslie A.
International Heart Journal 51(4), 277-284, 2010
… MEKK1 is a ubiquitously expressed mitogen activated protein kinase that is involved in tissue remodeling in a variety of settings including carotid artery blood flow cessation, wound healing, and breast adenocarcinoma intravasation. … Here, we have tested the function of MEKK1 in genetic hypertrophic cardiomyopathy (HCM). … MEKK1 was genetically deleted in C57Bl6/J mice expressing a mutant α-myosin heavy chain (HCM-MEKK1-/-). …
NAID 130000299284

Suppression of AP-1 Activity by Cycloprodigiosin Hydrochloride(Molecular and Cell Biology)

Kawauchi Keiko,Tobiume Kei,Kaneko Shuhei [他],KANESHIRO Keiko,OKAMOTO Shiho,UEDA Emi,KAMATA Hideaki,MORIYAMA Yoshinori,HIRATA Hajime
Biological & pharmaceutical bulletin 30(9), 1792-1795, 2007-09-01
… cPrG・HCl did not inhibit any of the mitogen-activated protein kinase (MAPK) families, whereas it did suppress transcriptional activation of AP-1 induced by constitutively activated mutants of MEKK1 or Ras. …
NAID 110006380271

MEKK1 is required for flg22-induced MPK4 activation in Arabidopsis plants

SUAREZ-RODRIGUEZ M. C.
Plant Physiol. 143, 661-669, 2007
NAID 80017879341

Related Pictures

MAP kinases and cell migration Figure 8. ,15,16. Vereinfachte Darstellung.MEKK1 CDK5 and MEKK1 mediate pro-apoptotic Figure 6 - Unfortunately we are unable to Skeletal muscle hypertrophy is regulated Innate Immunity AKT/GSK3 signaling pathway and

★リンクテーブル★

リンク元	「MEKキナーゼ1」「MEK kinase 1」
関連記事	「MEKK」

「MEKキナーゼ1」

Mitogen-activated protein kinase kinase kinase 1, E3 ubiquitin protein ligase
Identifiers
Symbols	MAP3K1; MAPKKK1; MEKK; MEKK 1; MEKK1; SRXY6
External IDs	OMIM: 600982 MGI: 1346872 HomoloGene: 8056 ChEMBL: 3956 GeneCards: MAP3K1 Gene
EC number	2.7.11.25
Gene Ontology
Molecular function	• protein kinase activity; • JUN kinase kinase kinase activity; • MAP kinase kinase kinase activity; • ubiquitin-protein ligase activity; • protein binding; • ATP binding; • zinc ion binding; • JUN kinase binding; • JUN kinase kinase activity; • protein kinase binding; • mitogen-activated protein kinase kinase binding; • identical protein binding; • sphingolipid binding; • metal ion binding; • mitogen-activated protein kinase binding;
Cellular component	• cytosol; • cytoskeleton;
Biological process	• protein polyubiquitination; • toll-like receptor signaling pathway; • MyD88-dependent toll-like receptor signaling pathway; • protein phosphorylation; • response to osmotic stress; • transforming growth factor beta receptor signaling pathway; • Toll signaling pathway; • apoptotic mitochondrial changes; • peptidyl-serine phosphorylation; • regulation of cell migration; • positive regulation of actin filament polymerization; • negative regulation of actin filament bundle assembly; • toll-like receptor 1 signaling pathway; • toll-like receptor 2 signaling pathway; • toll-like receptor 4 signaling pathway; • wound healing; • protein ubiquitination involved in ubiquitin-dependent protein catabolic process; • camera-type eye development; • positive regulation of apoptotic process; • innate immune response; • protein autophosphorylation; • positive regulation of viral transcription; • protein oligomerization; • cellular response to mechanical stimulus;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
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