MEK1

• MAPK-ERKキナーゼ1、MAPキナーゼキナーゼ1

関

MAP kinase kinase 1、MAPK-ERK kinase 1

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/03/18 15:02:33」(JST)

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Main article: Mitogen-activated protein kinase kinase

Mitogen-activated protein kinase kinase 1
PDB rendering based on 1s9j.
Available structures PDB Ortholog search: PDBe, RCSB List of PDB id codes 1S9J, 2P55, 3DV3, 3DY7, 3E8N, 3EQB, 3EQC, 3EQD, 3EQF, 3EQG, 3EQH, 3EQI, 3MBL, 3ORN, 3OS3, 3PP1, 3SLS, 3V01, 3V04, 3VVH, 3W8Q, 3ZLS, 3ZLW, 3ZLX, 3ZLY, 3ZM4, 4AN2, 4AN3, 4AN9, 4ANB, 4ARK, 4LMN
Identifiers
Symbols	MAP2K1 ; CFC3; MAPKK1; MEK1; MKK1; PRKMK1
External IDs	OMIM: 176872 MGI: 1346866 HomoloGene: 2063 ChEMBL: 3587 GeneCards: MAP2K1 Gene
EC number	2.7.12.2
Gene ontology Molecular function • protein kinase activity • protein serine/threonine kinase activity • MAP kinase kinase activity • protein serine/threonine/tyrosine kinase activity • protein tyrosine kinase activity • receptor signaling protein tyrosine phosphatase activity • protein binding • ATP binding • Ras GTPase binding • mitogen-activated protein kinase kinase kinase binding • protein serine/threonine kinase activator activity Cellular component • nucleus • cytoplasm • mitochondrion • early endosome • late endosome • Golgi apparatus • microtubule organizing center • cytosol • plasma membrane • focal adhesion • cell cortex • dendrite cytoplasm • perikaryon • perinuclear region of cytoplasm • extracellular vesicular exosome Biological process • MAPK cascade • activation of MAPKK activity • activation of MAPK activity • toll-like receptor signaling pathway • MyD88-dependent toll-like receptor signaling pathway • MyD88-independent toll-like receptor signaling pathway • regulation of vascular smooth muscle contraction • cellular component movement • chemotaxis • response to oxidative stress • cell cycle arrest • mitotic nuclear division • signal transduction • epidermal growth factor receptor signaling pathway • small GTPase mediated signal transduction • Ras protein signal transduction • axon guidance • cell proliferation • negative regulation of cell proliferation • insulin receptor signaling pathway • fibroblast growth factor receptor signaling pathway • positive regulation of gene expression • peptidyl-tyrosine phosphorylation • keratinocyte differentiation • positive regulation of cell migration • positive regulation of Ras GTPase activity • melanosome transport • regulation of stress-activated MAPK cascade • positive regulation of transcription elongation from RNA polymerase II promoter • negative regulation of homotypic cell-cell adhesion • toll-like receptor 2 signaling pathway • toll-like receptor 3 signaling pathway • toll-like receptor 4 signaling pathway • toll-like receptor 5 signaling pathway • toll-like receptor 9 signaling pathway • toll-like receptor 10 signaling pathway • TRIF-dependent toll-like receptor signaling pathway • Fc-epsilon receptor signaling pathway • toll-like receptor TLR1:TLR2 signaling pathway • toll-like receptor TLR6:TLR2 signaling pathway • innate immune response • positive regulation of cell differentiation • positive regulation of Ras protein signal transduction • vesicle transport along microtubule • neurotrophin TRK receptor signaling pathway • Golgi inheritance • response to axon injury • cell motility • protein heterooligomerization • response to glucocorticoid • stress-activated MAPK cascade • placenta blood vessel development • labyrinthine layer development • positive regulation of protein serine/threonine kinase activity • regulation of Golgi inheritance • cellular senescence • regulation of early endosome to late endosome transport Sources: Amigo / QuickGO
RNA expression pattern
More reference expression data
Orthologs
Species	Human	Mouse
Entrez	5604	26395
Ensembl	ENSG00000169032	ENSMUSG00000004936
UniProt	Q02750	P31938
RefSeq (mRNA)	NM_002755	NM_008927
RefSeq (protein)	NP_002746	NP_032953
Location (UCSC)	Chr 15: 66.68 – 66.78 Mb	Chr 9: 64.19 – 64.25 Mb
PubMed search	[1]	[2]

Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the MAP2K1 gene.

Function

The protein encoded by this gene is a member of the dual-specificity protein kinase family that acts 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 kinase lies upstream of MAP kinases and stimulates the enzymatic activity of MAP kinases upon activation by a wide variety of extra- and intracellular signals. As an essential component of the MAP kinase signal transduction pathway, this kinase is involved in many cellular processes such as proliferation, differentiation, transcription regulation and development.

Interactions

MAP2K1 has been shown to interact with C-Raf, Phosphatidylethanolamine binding protein 1, MAP2K1IP1, GRB10, MAPK3, MAPK8IP3, MAPK1 MP1, and MAP3K1.

References

Further reading

• Wu J, Michel H, Rossomando A, Haystead T, Shabanowitz J, Hunt DF, Sturgill TW. (1992). "Renaturation and partial peptide sequencing of mitogen-activated protein kinase (MAP kinase) activator from rabbit skeletal muscle". Biochem J. 285 (3): 701–5. PMC 1132850. PMID 1379797. 
• Rossomando AJ, Dent P, Sturgill TW, Marshak DR. (1994). "Mitogen-activated protein kinase kinase 1 (MKK1) is negatively regulated by threonine phosphorylation". Mol Cell Biol 14 (3): 1594–602. PMC 358518. PMID 8114697. 
• Seger R, Krebs EG (1995). "The MAPK signaling cascade". FASEB J. 9 (9): 726–35. PMID 7601337. 
• Joseph AM, Kumar M, Mitra D (2005). "Nef: "necessary and enforcing factor" in HIV infection". Curr. HIV Res. 3 (1): 87–94. doi:10.2174/1570162052773013. PMID 15638726. 
• Tanaka S, Nakamura K, Takahasi N, Suda T (2006). "Role of RANKL in physiological and pathological bone resorption and therapeutics targeting the RANKL-RANK signaling system". Immunol. Rev. 208: 30–49. doi:10.1111/j.0105-2896.2005.00327.x. PMID 16313339. 
• Stove V, Verhasselt B (2006). "Modelling thymic HIV-1 Nef effects". Curr. HIV Res. 4 (1): 57–64. doi:10.2174/157016206775197583. PMID 16454711. 
• Galabova-Kovacs G, Kolbus A, Matzen D, et al. (2006). "ERK and beyond: insights from B-Raf and Raf-1 conditional knockouts". Cell Cycle 5 (14): 1514–8. doi:10.4161/cc.5.14.2981. PMID 16861903. 

External links

• GeneReviews/NCBI/NIH/UW entry on Noonan syndrome
• GeneReviews/NCBI/NIH/UW entry on Cardiofaciocutaneous Syndrome

UpToDate Contents

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English Journal

• Sepsis protects the myocardium and other organs from subsequent ischaemic/reperfusion injury via a MAPK-dependent mechanism.

• Walshe CM1, Laffey JG, Kevin L, O'Toole D.
• Intensive care medicine experimental.Intensive Care Med Exp.2015 Dec;3(1):35. doi: 10.1186/s40635-014-0035-9. Epub 2015 Jan 31.
• BACKGROUND: Sepsis has been shown to precondition the intact heart against ischaemia/reperfusion (IR) injury, and prior endotoxin exposure of cells in in vitro models has shown evidence of protection against subsequent simulated ischaemia. Our aim in this study is to validate these findings and furt
• PMID 26215802

• Modulation of inflammatory mediators in the trigeminal ganglion by botulinum neurotoxin type A: an organ culture study.

• Edvinsson J1, Warfvinge K, Edvinsson L.
• The journal of headache and pain.J Headache Pain.2015 Dec;16(1):555. doi: 10.1186/s10194-015-0555-z. Epub 2015 Aug 6.
• BACKGROUND: Onabotulinumtoxin type A (BoNT-A) has been found to reduce pain in chronic migraine. The aim of the present study was to ask if BoNT-A can interact directly on sensory mechanisms in the trigeminal ganglion (TG) using an organ culture method.METHODS: To induce inflammation, rat TGs were i
• PMID 26245187

• Sequential phosphorylation analysis using dye-tethered peptides and microfluidic isoelectric focusing electrophoresis.

• Choi H1, Choi N2, Lim B1, Kim TW1, Song S3, Kim YP4.
• Biosensors & bioelectronics.Biosens Bioelectron.2015 Nov 15;73:93-9. doi: 10.1016/j.bios.2015.05.047. Epub 2015 May 25.
• We report a simple method for analyzing sequential phosphorylation by protein kinases using fluorescent peptide substrates and microfluidic isoelectric focusing (μIEF) electrophoresis. When a dye-labeled peptide substrate was sequentially phosphorylated by two consecutive protein kinases (mitogen-a
• PMID 26050965

Japanese Journal

• Nicotinamide Prevents the Down-Regulation of MEK/ERK/p90RSK Signaling Cascade in Brain Ischemic Injury

• SUNG Jin-Hee,KIM Myeong-Ok,KOH Phil-Ok
• Journal of Veterinary Medical Science 74(1), 35-41, 2012
• … Nicotinamide prevents injury-induced decrease in Raf-1, MEK1/2, and ERK1/2 phosphorylation. …
• NAID 130001032922

• High Dose of Pyridoxine Induces IGFBP-3 mRNA Expression in MCF-7 Cells and Its Induction Is Inhibited by the p53-Specific Inhibitor Pifithrin-.ALPHA.

• Nakari Miwa,Kanouchi Hiroaki,Oka Tatsuzo
• Journal of Nutritional Science and Vitaminology 57(4), 280-284, 2011
• … The induction of IGFBP-3 by PN was inhibited by a p53-specific inhibitor, pifithrin-α, in a dose-dependent manner, but was not affected by PD169316 (MAPK inhibitor), AS601245 (c-Jun N-terminal kinase inhibitor) or SL327 (MEK1/2 inhibitor). …
• NAID 130001372999

• Mechanism of Pigmentation by Minocycline in Murine B16 Melanoma Cells

• 佐藤 恵美,月本 光俊,志村 紀子 [他],粟屋 昭,小島 周二
• 薬学雑誌 131(5), 731-738, 2011
• … The mitogen-activated protein kinase kinase 1/2 (MEK1/2) inhibitor U0126 and the p38 inhibitor SB203580 were used to examine the signaling pathway associated with the mRNA expression of tyrosinase, TRP-1, or TRP-2 when B16 melanoma cells were treated with minocycline. …
• NAID 130000678855

Related Pictures

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★リンクテーブル★

リンク元	「MAPキナーゼスーパーファミリーカスケード」「MAPキナーゼキナーゼ1」「MAP kinase kinase 1」「MAPK-ERK kinase 1」「MAPK-ERKキナーゼ1」
関連記事	「ME」

「MAPキナーゼスーパーファミリーカスケード」

　　[★]

層	増殖因子
細胞膜	Grb2 Sos Ras
細胞質
MAPKKKK	PAK3
MAPKKK	Raf-1/A-Raf
MAPKK	B-Raf/Mos
MAPK	MEK1/MEK2
基質	ERK1/ERK2, p90rsk, MNK1/MNK2, Sos, cPLA2, EGFR, Elk-1, Ets1, Sap1a, STAT, Map2, Tau

「MAPキナーゼキナーゼ1」

　　[★]

英

MAP kinase kinase 1、MAPK-ERK kinase 1、MEK1

関

MAPK-ERKキナーゼ1、マイトジェン活性化プロテインキナーゼキナーゼ1

「MAP kinase kinase 1」

　　[★]

• MAPキナーゼキナーゼ1

関

MAPK-ERK kinase 1、MEK1、mitogen-activated protein kinase kinase 1

「MAPK-ERK kinase 1」

　　[★]

• MAPK-ERKキナーゼ1、MAPキナーゼキナーゼ1

関

MAP kinase kinase 1、MEK1

「MAPK-ERKキナーゼ1」

　　[★]

英

MAPK-ERK kinase 1、MEK1

関

MAPキナーゼキナーゼ1

「ME」

　　[★]

• 医用電子工学、医用工学

関

medical electronics、medical engineering