関: MAP kinase kinase 1

WordNet

aerate (sewage) so as to favor the growth of organisms that decompose organic matter (同)aerate
make (substances) radioactive
make active or more active; "activate an old file"
make more adsorptive; "activate a metal"
rendered active; e.g. rendered radioactive or luminescent or photosensitive or conductive
(of e.g. a molecule) made reactive or more reactive (同)excited
(military) set up and placed on active assignment; "a newly activated unit"
(of sewage) treated with aeration and bacteria to aid decomposition
any of a large group of nitrogenous organic compounds that are essential constituents of living cells; consist of polymers of amino acids; essential in the diet of animals for growth and for repair of tissues; can be obtained from meat and eggs and milk and legumes; "a diet high in protein"
an enzyme that catalyzes the conversion of a proenzyme to an active enzyme
an agent that triggers mitosis

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2012/07/27 12:26:52」(JST)

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Main article: Mitogen-activated protein kinase kinase

Dual specificity mitogen-activated protein kinase kinase 1 is an enzyme that in humans is encoded by the MAP2K1 gene.^[1]^[2]

Function

The protein encoded by this gene is a member of the dual specificity protein kinase family, which 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.^[3]

Interactions

MAP2K1 has been shown to interact with C-Raf,^[4] Phosphatidylethanolamine binding protein 1,^[4] MAP2K1IP1,^[5]^[6] GRB10,^[7] MAPK3,^[6]^[8]^[9]^[10]^[11] MAPK8IP3,^[12]^[13] MAPK1^[4]^[5]^[14]^[15]^[16]^[17] MP1,^[6] and MAP3K1.^[18]

References

^ Rampoldi L, Zimbello R, Bortoluzzi S, Tiso N, Valle G, Lanfranchi G, Danieli GA (Mar 1998). "Chromosomal localization of four MAPK signaling cascade genes: MEK1, MEK3, MEK4 and MEKK5". Cytogenet Cell Genet 78 (3–4): 301–3. DOI:10.1159/000134677. PMID 9465908.
^ Zheng CF, Guan KL (Jun 1993). "Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2". J Biol Chem 268 (15): 11435–9. PMID 8388392.
^ "Entrez Gene: MAP2K1 mitogen-activated protein kinase kinase 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5604.
^ ^a ^b ^c Yeung, K; Janosch P, McFerran B, Rose D W, Mischak H, Sedivy J M, Kolch W (May. 2000). "Mechanism of Suppression of the Raf/MEK/Extracellular Signal-Regulated Kinase Pathway by the Raf Kinase Inhibitor Protein". Mol. Cell. Biol. (UNITED STATES) 20 (9): 3079–85. DOI:10.1128/MCB.20.9.3079-3085.2000. PMC 85596. PMID 10757792. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85596.
^ ^a ^b Wunderlich, W; Fialka I, Teis D, Alpi A, Pfeifer A, Parton R G, Lottspeich F, Huber L A (Feb. 2001). "A Novel 14-Kilodalton Protein Interacts with the Mitogen-Activated Protein Kinase Scaffold Mp1 on a Late Endosomal/Lysosomal Compartment". J. Cell Biol. (United States) 152 (4): 765–76. DOI:10.1083/jcb.152.4.765. PMC 2195784. PMID 11266467. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2195784.
^ ^a ^b ^c Schaeffer, H J; Catling A D, Eblen S T, Collier L S, Krauss A, Weber M J (Sep. 1998). "MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade". Science (UNITED STATES) 281 (5383): 1668–71. DOI:10.1126/science.281.5383.1668. PMID 9733512.
^ Nantel, A; Mohammad-Ali K, Sherk J, Posner B I, Thomas D Y (Apr. 1998). "Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases". J. Biol. Chem. (UNITED STATES) 273 (17): 10475–84. DOI:10.1074/jbc.273.17.10475. PMID 9553107.
^ Marti, A; Luo Z, Cunningham C, Ohta Y, Hartwig J, Stossel T P, Kyriakis J M, Avruch J (Jan. 1997). "Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells". J. Biol. Chem. (UNITED STATES) 272 (5): 2620–8. DOI:10.1074/jbc.272.5.2620. PMID 9006895.
^ Butch, E R; Guan K L (Feb. 1996). "Characterization of ERK1 activation site mutants and the effect on recognition by MEK1 and MEK2". J. Biol. Chem. (UNITED STATES) 271 (8): 4230–5. DOI:10.1074/jbc.271.8.4230. PMID 8626767.
^ Yung, Y; Yao Z, Hanoch T, Seger R (May. 2000). "ERK1b, a 46-kDa ERK isoform that is differentially regulated by MEK". J. Biol. Chem. (UNITED STATES) 275 (21): 15799–808. DOI:10.1074/jbc.M910060199. PMID 10748187.
^ Zheng, C F; Guan K L (Nov. 1993). "Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases". J. Biol. Chem. (UNITED STATES) 268 (32): 23933–9. PMID 8226933.
^ Kuboki, Y; Ito M, Takamatsu N, Yamamoto K I, Shiba T, Yoshioka K (Dec. 2000). "A scaffold protein in the c-Jun NH2-terminal kinase signaling pathways suppresses the extracellular signal-regulated kinase signaling pathways". J. Biol. Chem. (UNITED STATES) 275 (51): 39815–8. DOI:10.1074/jbc.C000403200. PMID 11044439.
^ Ito, M; Yoshioka K, Akechi M, Yamashita S, Takamatsu N, Sugiyama K, Hibi M, Nakabeppu Y, Shiba T, Yamamoto K I (Nov. 1999). "JSAP1, a Novel Jun N-Terminal Protein Kinase (JNK)-Binding Protein That Functions as a Scaffold Factor in the JNK Signaling Pathway". Mol. Cell. Biol. (UNITED STATES) 19 (11): 7539–48. PMC 84763. PMID 10523642. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84763.
^ Sanz-Moreno, Victoria; Casar Berta, Crespo Piero (May. 2003). "p38α 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". Mol. Cell. Biol. (United States) 23 (9): 3079–90. DOI:10.1128/MCB.23.9.3079-3090.2003. PMC 153192. PMID 12697810. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=153192.
^ Robinson, Fred L; Whitehurst Angelique W, Raman Malavika, Cobb Melanie H (Apr. 2002). "Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1". J. Biol. Chem. (United States) 277 (17): 14844–52. DOI:10.1074/jbc.M107776200. PMID 11823456.
^ Xu Be, Be; Stippec S, Robinson F L, Cobb M H (Jul. 2001). "Hydrophobic as well as charged residues in both MEK1 and ERK2 are important for their proper docking". J. Biol. Chem. (United States) 276 (28): 26509–15. DOI:10.1074/jbc.M102769200. PMID 11352917.
^ Chen, Z; Cobb M H (May. 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. (United States) 276 (19): 16070–5. DOI:10.1074/jbc.M100681200. PMID 11279118.
^ Karandikar, M; Xu S, Cobb M H (Dec. 2000). "MEKK1 binds raf-1 and the ERK2 cascade components". J. Biol. Chem. (UNITED STATES) 275 (51): 40120–7. DOI:10.1074/jbc.M005926200. PMID 10969079.

External links

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

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English Journal

MEK1/2 overactivation can promote growth arrest by mediating ERK1/2-dependent phosphorylation of p70S6K.

Guégan JP1, Ezan F, Gailhouste L, Langouët S, Baffet G.
Journal of cellular physiology.J Cell Physiol.2014 Jul;229(7):903-15. doi: 10.1002/jcp.24521.
The extracellular signal-regulated kinase (ERK)1/2 mitogen-activated protein (MAP) kinase pathway has been involved in the positive and negative regulation of cell proliferation. Upon mitogen stimulation, ERK1/ERK2 activation is necessary for G1- to S-phase progression whereas when hyperactived, thi
PMID 24501087

Epithelial-mesenchymal transition in human gastric cancer cell lines induced by TNF-α-inducing protein of Helicobacter pylori.

Watanabe T1, Takahashi A, Suzuki K, Kurusu-Kanno M, Yamaguchi K, Fujiki H, Suganuma M.
International journal of cancer. Journal international du cancer.Int J Cancer.2014 May 15;134(10):2373-82. doi: 10.1002/ijc.28582. Epub 2013 Nov 19.
Helicobacter pylori strains produce tumor necrosis factor-α (TNF-α)-inducing protein, Tipα as a carcinogenic factor in the gastric epithelium. Tipα acts as a homodimer with 38-kDa protein, whereas del-Tipα is an inactive monomer. H. pylori isolated from gastric cancer patients secreted large am
PMID 24249671

U0126, a mitogen-activated protein kinase kinase 1 and 2 (MEK1 and 2) inhibitor, selectively up-regulates main isoforms of CYP3A subfamily via a pregnane X receptor (PXR) in HepG2 cells.

Smutny T1, Bitman M, Urban M, Dubecka M, Vrzal R, Dvorak Z, Pavek P.
Archives of toxicology.Arch Toxicol.2014 May 14. [Epub ahead of print]
Hepatocyte tumor cell lines lack the expression or induction properties of major cytochrome P450 (CYP) enzymes compared to primary human hepatocytes. The Ras/Raf/MEK/ERK signaling cascade contributes to hepatocarcinogenesis, dedifferentiation and loss of hepatocyte drug metabolism in hepatocyte tumo
PMID 24819614

Japanese Journal

Angiotensin II produces nociceptive behavior through spinal AT1 receptor-mediated p38 mitogen-activated protein kinase activation in mice

Nemoto Wataru,Nakagawasai Osamu,Yaoita Fukie,Kanno Syu-Ichi,Yomogida Shin,Ishikawa Masaaki,Tadano Takeshi,Tana-No Koichi
Molecular Pain 9(1), 38, 2013-07-31
Background: It has been demonstrated that angiotensin II (Ang II) participates in either the inhibition or the facilitation of nociceptive transmission depending on the brain area. Neuronal Ang II is …
NAID 120005328804

ROS Are Required for Mouse Spermatogonial Stem Cell Self-Renewal

Morimoto Hiroko,Iwata Kazumi,Ogonuki Narumi,Inoue Kimiko,Ogura Atsuo,Kanatsu-Shinohara Mito,Morimoto Takeshi,Yabe-Nishimura Chihiro,Shinohara Takashi
Cell Stem Cell 12(6), 774-786, 2013-06-00
… SSCs depleted of ROS stopped proliferating, but they showed enhanced self-renewal when ROS levels were increased by the addition of hydrogen peroxide, which induced the phosphorylation of stress kinases p38 mitogen-activated protein kinase (MAPK) and c-jun N-terminal kinase (JNK). …
NAID 120005285490

Roles of FGF20 in dopaminergic neurons and Parkinson's disease.

Itoh Nobuyuki,Ohta Hiroya
Frontiers in molecular neuroscience 6, 2013-05-00
… Fgf20, which acts on proximal cells, significantly enhanced the survival of cultured dopaminergic neurons by activating the mitogen-activated protein kinase (MAPK) pathway through Fgf receptor 1c. …
NAID 120005289845

「MAP kinase kinase 1」

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
Identifiers
Symbols	MAP2K1; 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;
Cellular component	• soluble fraction; • nucleus; • cytoplasm; • mitochondrion; • early endosome; • late endosome; • Golgi apparatus; • spindle pole body; • cytosol; • microtubule; • plasma membrane; • focal adhesion; • cell cortex; • dendrite cytoplasm; • axon part; • perikaryon; • perinuclear region of cytoplasm;
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; • mitosis; • signal transduction; • epidermal growth factor receptor signaling pathway; • small GTPase mediated signal transduction; • Ras protein signal transduction; • axon guidance; • Toll signaling pathway; • cell proliferation; • negative regulation of cell proliferation; • insulin receptor signaling pathway; • fibroblast growth factor receptor signaling pathway; • 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 1 signaling pathway; • toll-like receptor 2 signaling pathway; • toll-like receptor 3 signaling pathway; • toll-like receptor 4 signaling pathway; • TRIF-dependent toll-like receptor signaling pathway; • innate immune response; • positive regulation of cell differentiation; • positive regulation of Ras protein signal transduction; • vesicle transport along microtubule; • nerve growth factor receptor signaling pathway; • Golgi inheritance; • response to axon injury; • cell motility; • response to glucocorticoid stimulus; • stress-activated MAPK cascade; • placenta blood vessel development; • labyrinthine layer development; • 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
	This box: view; talk; edit;

　　[★]

MAPキナーゼキナーゼ1

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

「マイトジェン活性化プロテインキナーゼキナーゼ1」

　　[★]

英: mitogen-activated protein kinase kinase 1
関: MAPキナーゼキナーゼ1

「activated」

　　[★]

adj.

活性化の、活性化型の、賦活化の

関: activate、activated form、activation、turn on

「activate」

　　[★]

v.

活性化する、賦活化する、賦活する

関: activated、activation、turn on

「kinase」

　　[★] キナーゼカイネースリン酸化酵素 phosphoenzyme phosphotransferase 　

「protein kinase」

　　[★] プロテインキナーゼ

同: protein kinases

[pmid9465908-0] Rampoldi L, Zimbello R, Bortoluzzi S, Tiso N, Valle G, Lanfranchi G, Danieli GA (Mar 1998). "Chromosomal localization of four MAPK signaling cascade genes: MEK1, MEK3, MEK4 and MEKK5". Cytogenet Cell Genet 78 (3–4): 301–3. DOI:10.1159/000134677. PMID 9465908.

[pmid8388392-1] Zheng CF, Guan KL (Jun 1993). "Cloning and characterization of two distinct human extracellular signal-regulated kinase activator kinases, MEK1 and MEK2". J Biol Chem 268 (15): 11435–9. PMID 8388392.

[2] "Entrez Gene: MAP2K1 mitogen-activated protein kinase kinase 1". http://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=5604.

[pmid10757792-3] Yeung, K; Janosch P, McFerran B, Rose D W, Mischak H, Sedivy J M, Kolch W (May. 2000). "Mechanism of Suppression of the Raf/MEK/Extracellular Signal-Regulated Kinase Pathway by the Raf Kinase Inhibitor Protein". Mol. Cell. Biol. (UNITED STATES) 20 (9): 3079–85. DOI:10.1128/MCB.20.9.3079-3085.2000. PMC 85596. PMID 10757792. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=85596.

[pmid11266467-4] Wunderlich, W; Fialka I, Teis D, Alpi A, Pfeifer A, Parton R G, Lottspeich F, Huber L A (Feb. 2001). "A Novel 14-Kilodalton Protein Interacts with the Mitogen-Activated Protein Kinase Scaffold Mp1 on a Late Endosomal/Lysosomal Compartment". J. Cell Biol. (United States) 152 (4): 765–76. DOI:10.1083/jcb.152.4.765. PMC 2195784. PMID 11266467. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=2195784.

[pmid9733512-5] Schaeffer, H J; Catling A D, Eblen S T, Collier L S, Krauss A, Weber M J (Sep. 1998). "MP1: a MEK binding partner that enhances enzymatic activation of the MAP kinase cascade". Science (UNITED STATES) 281 (5383): 1668–71. DOI:10.1126/science.281.5383.1668. PMID 9733512.

[pmid9553107-6] Nantel, A; Mohammad-Ali K, Sherk J, Posner B I, Thomas D Y (Apr. 1998). "Interaction of the Grb10 adapter protein with the Raf1 and MEK1 kinases". J. Biol. Chem. (UNITED STATES) 273 (17): 10475–84. DOI:10.1074/jbc.273.17.10475. PMID 9553107.

[pmid9006895-7] Marti, A; Luo Z, Cunningham C, Ohta Y, Hartwig J, Stossel T P, Kyriakis J M, Avruch J (Jan. 1997). "Actin-binding protein-280 binds the stress-activated protein kinase (SAPK) activator SEK-1 and is required for tumor necrosis factor-alpha activation of SAPK in melanoma cells". J. Biol. Chem. (UNITED STATES) 272 (5): 2620–8. DOI:10.1074/jbc.272.5.2620. PMID 9006895.

[pmid8626767-8] Butch, E R; Guan K L (Feb. 1996). "Characterization of ERK1 activation site mutants and the effect on recognition by MEK1 and MEK2". J. Biol. Chem. (UNITED STATES) 271 (8): 4230–5. DOI:10.1074/jbc.271.8.4230. PMID 8626767.

[pmid10748187-9] Yung, Y; Yao Z, Hanoch T, Seger R (May. 2000). "ERK1b, a 46-kDa ERK isoform that is differentially regulated by MEK". J. Biol. Chem. (UNITED STATES) 275 (21): 15799–808. DOI:10.1074/jbc.M910060199. PMID 10748187.

[pmid8226933-10] Zheng, C F; Guan K L (Nov. 1993). "Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases". J. Biol. Chem. (UNITED STATES) 268 (32): 23933–9. PMID 8226933.

[pmid11044439-11] Kuboki, Y; Ito M, Takamatsu N, Yamamoto K I, Shiba T, Yoshioka K (Dec. 2000). "A scaffold protein in the c-Jun NH2-terminal kinase signaling pathways suppresses the extracellular signal-regulated kinase signaling pathways". J. Biol. Chem. (UNITED STATES) 275 (51): 39815–8. DOI:10.1074/jbc.C000403200. PMID 11044439.

[pmid10523642-12] Ito, M; Yoshioka K, Akechi M, Yamashita S, Takamatsu N, Sugiyama K, Hibi M, Nakabeppu Y, Shiba T, Yamamoto K I (Nov. 1999). "JSAP1, a Novel Jun N-Terminal Protein Kinase (JNK)-Binding Protein That Functions as a Scaffold Factor in the JNK Signaling Pathway". Mol. Cell. Biol. (UNITED STATES) 19 (11): 7539–48. PMC 84763. PMID 10523642. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=84763.

[pmid12697810-13] Sanz-Moreno, Victoria; Casar Berta, Crespo Piero (May. 2003). "p38α 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". Mol. Cell. Biol. (United States) 23 (9): 3079–90. DOI:10.1128/MCB.23.9.3079-3090.2003. PMC 153192. PMID 12697810. //www.pubmedcentral.nih.gov/articlerender.fcgi?tool=pmcentrez&artid=153192.

[pmid11823456-14] Robinson, Fred L; Whitehurst Angelique W, Raman Malavika, Cobb Melanie H (Apr. 2002). "Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1". J. Biol. Chem. (United States) 277 (17): 14844–52. DOI:10.1074/jbc.M107776200. PMID 11823456.

[pmid11352917-15] Xu Be, Be; Stippec S, Robinson F L, Cobb M H (Jul. 2001). "Hydrophobic as well as charged residues in both MEK1 and ERK2 are important for their proper docking". J. Biol. Chem. (United States) 276 (28): 26509–15. DOI:10.1074/jbc.M102769200. PMID 11352917.

[pmid11279118-16] Chen, Z; Cobb M H (May. 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. (United States) 276 (19): 16070–5. DOI:10.1074/jbc.M100681200. PMID 11279118.

[pmid10969079-17] Karandikar, M; Xu S, Cobb M H (Dec. 2000). "MEKK1 binds raf-1 and the ERK2 cascade components". J. Biol. Chem. (UNITED STATES) 275 (51): 40120–7. DOI:10.1074/jbc.M005926200. PMID 10969079.

リンク元	「MAP kinase kinase 1」「マイトジェン活性化プロテインキナーゼキナーゼ1」
関連記事	「activated」「activate」「kinase」「protein kinase」

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案内

mitogen-activated protein kinase kinase 1