同: 細胞外シグナル制御キナーゼ1, extracellular signal-regulated kinase 1
関: ERK

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出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2016/02/07 20:37:21」(JST)

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Mitogen-activated protein kinase 3 is an enzyme that in humans is encoded by the MAPK3 gene.^[1]

Function

The protein encoded by this gene is a member of the MAP kinase family. MAP kinases, also known as extracellular signal-regulated kinases (ERKs), act in a signaling cascade that regulates various cellular processes such as proliferation, differentiation, and cell cycle progression in response to a variety of extracellular signals. This kinase is activated by upstream kinases, resulting in its translocation to the nucleus where it phosphorylates nuclear targets. Alternatively spliced transcript variants encoding different protein isoforms have been described.^[2]

Clinical significance

It has been suggested that MAPK3, along with the gene IRAK1, is turned off by two microRNAs that were activated after the influenza A virus had been made to infect human lung cells.^[3]

Interactions

MAPK3 has been shown to interact with:

DUSP3,^[4]
DUSP6^[5]
GTF2I,^[6]
HDAC4,^[7]
MAP2K1,^[8]^[9]^[10]^[11]^[12]
MAP2K2,^[8]^[9]^[12]
PTPN7,^[13]^[14]^[15]
RPS6KA2,^[16]^[17] and
SPIB.^[18]

References

^ García F, Zalba G, Páez G, Encío I, de Miguel C (15 May 1998). "Molecular cloning and characterization of the human p44 mitogen-activated protein kinase gene". Genomics 50 (1): 69–78. doi:10.1006/geno.1998.5315. PMID 9628824.
^ "Entrez Gene: MAPK3 mitogen-activated protein kinase 3".
^ Buggele WA, Johnson KE, Horvath CM (2012). "Influenza A virus infection of human respiratory cells induces primary microRNA expression". J. Biol. Chem. 287 (37): 31027–40. doi:10.1074/jbc.M112.387670. PMC 3438935. PMID 22822053.
^ Todd JL, Tanner KG, Denu JM (May 1999). "Extracellular regulated kinases (ERK) 1 and ERK2 are authentic substrates for the dual-specificity protein-tyrosine phosphatase VHR. A novel role in down-regulating the ERK pathway". J. Biol. Chem. 274 (19): 13271–80. doi:10.1074/jbc.274.19.13271. PMID 10224087.
^ Muda M, Theodosiou A, Gillieron C, Smith A, Chabert C, Camps M, Boschert U, Rodrigues N, Davies K, Ashworth A, Arkinstall S (April 1998). "The mitogen-activated protein kinase phosphatase-3 N-terminal noncatalytic region is responsible for tight substrate binding and enzymatic specificity". J. Biol. Chem. 273 (15): 9323–9. doi:10.1074/jbc.273.15.9323. PMID 9535927.
^ Kim DW, Cochran BH (February 2000). "Extracellular signal-regulated kinase binds to TFII-I and regulates its activation of the c-fos promoter". Mol. Cell. Biol. 20 (4): 1140–8. doi:10.1128/mcb.20.4.1140-1148.2000. PMC 85232. PMID 10648599.
^ Zhou X, Richon VM, Wang AH, Yang XJ, Rifkind RA, Marks PA (December 2000). "Histone deacetylase 4 associates with extracellular signal-regulated kinases 1 and 2, and its cellular localization is regulated by oncogenic Ras". Proc. Natl. Acad. Sci. U.S.A. 97 (26): 14329–33. doi:10.1073/pnas.250494697. PMC 18918. PMID 11114188.
^ ^a ^b Marti A, Luo Z, Cunningham C, Ohta Y, Hartwig J, Stossel TP, Kyriakis JM, Avruch J (January 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. 272 (5): 2620–8. doi:10.1074/jbc.272.5.2620. PMID 9006895.
^ ^a ^b Butch ER, Guan KL (February 1996). "Characterization of ERK1 activation site mutants and the effect on recognition by MEK1 and MEK2". J. Biol. Chem. 271 (8): 4230–5. doi:10.1074/jbc.271.8.4230. PMID 8626767.
^ Elion EA (September 1998). "Routing MAP kinase cascades". Science 281 (5383): 1625–6. doi:10.1126/science.281.5383.1625. PMID 9767029.
^ 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. 275 (21): 15799–808. doi:10.1074/jbc.M910060199. PMID 10748187.
^ ^a ^b Zheng CF, Guan KL (November 1993). "Properties of MEKs, the kinases that phosphorylate and activate the extracellular signal-regulated kinases". J. Biol. Chem. 268 (32): 23933–9. PMID 8226933.
^ Pettiford SM, Herbst R (February 2000). "The MAP-kinase ERK2 is a specific substrate of the protein tyrosine phosphatase HePTP". Oncogene 19 (7): 858–69. doi:10.1038/sj.onc.1203408. PMID 10702794.
^ Saxena M, Williams S, Taskén K, Mustelin T (September 1999). "Crosstalk between cAMP-dependent kinase and MAP kinase through a protein tyrosine phosphatase". Nat. Cell Biol. 1 (5): 305–11. doi:10.1038/13024. PMID 10559944.
^ Saxena M, Williams S, Brockdorff J, Gilman J, Mustelin T (April 1999). "Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP)". J. Biol. Chem. 274 (17): 11693–700. doi:10.1074/jbc.274.17.11693. PMID 10206983.
^ Roux PP, Richards SA, Blenis J (July 2003). "Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity". Mol. Cell. Biol. 23 (14): 4796–804. doi:10.1128/mcb.23.14.4796-4804.2003. PMC 162206. PMID 12832467.
^ Zhao Y, Bjorbaek C, Moller DE (November 1996). "Regulation and interaction of pp90(rsk) isoforms with mitogen-activated protein kinases". J. Biol. Chem. 271 (47): 29773–9. doi:10.1074/jbc.271.47.29773. PMID 8939914.
^ Mao C, Ray-Gallet D, Tavitian A, Moreau-Gachelin F (February 1996). "Differential phosphorylations of Spi-B and Spi-1 transcription factors". Oncogene 12 (4): 863–73. PMID 8632909.

External links

MAP Kinase Resource .

Molecular and Cellular Biology portal

This article on a gene on human chromosome 16 is a stub. You can help Wikipedia by expanding it.

UpToDate Contents

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English Journal

Antitumor efficacy of piperine in the treatment of human HER2-overexpressing breast cancer cells.

Do MT, Kim HG, Choi JH, Khanal T, Park BH, Tran TP, Jeong TC, Jeong HG.SourceDepartment of Toxicology, College of Pharmacy, Chungnam National University, Daejeon 305-764, South Korea.
Food chemistry.Food Chem.2013 Dec 1;141(3):2591-9. doi: 10.1016/j.foodchem.2013.04.125. Epub 2013 May 24.
Piperine is a bioactive component of black pepper, Piper nigrum Linn, commonly used for daily consumption and in traditional medicine. Here, the molecular mechanisms by which piperine exerts antitumor effects in HER2-overexpressing breast cancer cells was investigated. The results showed that piperi
PMID 23870999

Estrogen up-regulates MMP2/9 expression in endometrial epithelial cell via VEGF-ERK1/2 pathway.

Shan B, Li W, Yang SY, Li ZR.SourceDepartment of Gynaecology and Obstetrics of Hainan People's Hospital, Hai Kou 570311, China.
Asian Pacific journal of tropical medicine.Asian Pac J Trop Med.2013 Oct;6(10):826-30. doi: 10.1016/S1995-7645(13)60146-7.
OBJECTIVE: To study the effect of estrogen on anovulatory dysfunctional uterine bleeding (ADUB).METHODS: Primary endometrial epithelial cells of Hainan Lizu female was cultured and hydrolytic activity of gelatinase was determined by gelatin zymography analysis. Cellular mRNA and protein synthesis wa
PMID 23870474

The three α1-adrenoceptor subtypes show different spatio-temporal mechanisms of internalization and ERK1/2 phosphorylation.

Perez-Aso M, Segura V, Montó F, Barettino D, Noguera MA, Milligan G, D'Ocon P.SourceDepartament de Farmacologia, Universitat de València, Spain.
Biochimica et biophysica acta.Biochim Biophys Acta.2013 Oct;1833(10):2322-33. doi: 10.1016/j.bbamcr.2013.06.013. Epub 2013 Jun 21.
We analyzed the kinetic and spatial patterns characterizing activation of the MAP kinases ERK 1 and 2 (ERK1/2) by the three α1-adrenoceptor (α1-AR) subtypes in HEK293 cells and the contribution of two different pathways to ERK1/2 phosphorylation: protein kinase C (PKC)-dependent ERK1/2 activation
PMID 23797059

Japanese Journal

地域特産野菜「ウコギ」の皮膚保護作用の探索(第一報)

仁科淳良,加藤守匡,寺嶋康正,森田幸雄,木村博一,ニシナアツヨシ,カトウモリマサ,テラシマヤスマサ,モリタユキオ,キムラヒロカズ,Nishina Atsuyoshi,Kato Morimasa,Terashima Yasumasa,Morita Yukio,Kimura Hirokazu
山形県立米沢女子短期大学紀要 = Bulletin of Yonezawa Women's Junior College 47, 23-38, 2011-12-26
… フラクションFをHaCaT細胞の培地に添加することにより、AktとERK1/2のリン酸化が有意に亢進することが分かった。 … また、阻害剤により、フラクションFによるAktとERK1/2のリン酸化を阻害すると、皮膚保護作用も消失したことから、フラクションFはAktとERK1/2を活性化してHaCaT細胞のUVBによるアボトーシスを抑制していると判断した。 …
NAID 120003809398

Bisphenol-A suppresses neurite extension due to inhibition of phosphorylation of mitogen-activated protein kinase in PC12 cells

Seki Sayaka,Aoki Miho,Hosokawa Toshiyuki,Saito Takeshi,Masuma Runa,Komori Miyako,Kurasaki Masaaki
Chemico-Biological Interactions 194(1), 23-30, 2011-10-15
… As results, bisphenol-A significantly inhibited phosphorylation of CREB and ERK1/2 MAPK. …
NAID 120003483496

Related Pictures

Total-ERK1/2 Cellular Assay Kit | Cisbio Erk1/2 MAPK−triggered stimulation of IFN www.jhoonline.org - Figure Oncogene - Figure 4 for article: Molecular apoptotic and vasodilator responses erk1 2 egf receptor endocytosis and erk1 ERK1/2 pathway - Humpath.com - Human Processing of a Homogeneous Phospho-ERK1

★リンクテーブル★

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

「MAPキナーゼ」

Mitogen-activated protein kinase 3
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	2ZOQ, 4QTB
Identifiers
Symbols	MAPK3 ; ERK-1; ERK1; ERT2; HS44KDAP; HUMKER1A; P44ERK1; P44MAPK; PRKM3; p44-ERK1; p44-MAPK
External IDs	OMIM: 601795 MGI: 1346859 HomoloGene: 55682 ChEMBL: 3385 GeneCards: MAPK3 Gene
EC number	2.7.11.24
Gene ontology
Molecular function	• phosphotyrosine binding; • MAP kinase activity; • protein binding; • ATP binding; • phosphatase binding; • scaffold protein binding;
Cellular component	• nucleus; • nuclear envelope; • nucleoplasm; • mitochondrion; • early endosome; • late endosome; • Golgi apparatus; • cytosol; • cytoskeleton; • caveola; • focal adhesion; • microtubule cytoskeleton; • pseudopodium; • protein complex; • extracellular exosome;
Biological process	• MAPK cascade; • activation of MAPKK activity; • activation of MAPK activity; • MAPK import into nucleus; • positive regulation of protein phosphorylation; • toll-like receptor signaling pathway; • MyD88-dependent toll-like receptor signaling pathway; • MyD88-independent toll-like receptor signaling pathway; • transcription from RNA polymerase I promoter; • transcription initiation from RNA polymerase I promoter; • protein complex assembly; • protein phosphorylation; • apoptotic process; • DNA damage induced protein phosphorylation; • cell cycle; • epidermal growth factor receptor signaling pathway; • small GTPase mediated signal transduction; • Ras protein signal transduction; • axon guidance; • blood coagulation; • insulin receptor signaling pathway; • fibroblast growth factor receptor signaling pathway; • response to toxic substance; • gene expression; • viral process; • phosphorylation; • peptidyl-serine phosphorylation; • cytokine-mediated signaling pathway; • sensory perception of pain; • arachidonic acid metabolic process; • platelet activation; • BMP signaling pathway; • positive regulation of cyclase activity; • lipopolysaccharide-mediated signaling pathway; • regulation of stress-activated MAPK cascade; • positive regulation of histone phosphorylation; • 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; • cellular response to heat; • positive regulation of histone acetylation; • TRIF-dependent toll-like receptor signaling pathway; • peptidyl-tyrosine autophosphorylation; • Fc-epsilon receptor signaling pathway; • Fc-gamma receptor signaling pathway involved in phagocytosis; • toll-like receptor TLR1:TLR2 signaling pathway; • toll-like receptor TLR6:TLR2 signaling pathway; • response to exogenous dsRNA; • innate immune response; • positive regulation of translation; • positive regulation of transcription from RNA polymerase II promoter; • vascular endothelial growth factor receptor signaling pathway; • neurotrophin TRK receptor signaling pathway; • regulation of sequence-specific DNA binding transcription factor activity; • cartilage development; • stress-activated MAPK cascade; • regulation of cytoskeleton organization; • JAK-STAT cascade involved in growth hormone signaling pathway; • lung morphogenesis; • trachea formation; • ERK1 and ERK2 cascade; • positive regulation of ERK1 and ERK2 cascade; • interleukin-1-mediated signaling pathway; • response to epidermal growth factor; • cellular response to mechanical stimulus; • caveolin-mediated endocytosis; • regulation of Golgi inheritance; • regulation of cellular response to heat; • regulation of early endosome to late endosome transport; • negative regulation of apolipoprotein binding;
	Sources: Amigo / QuickGO
RNA expression pattern
	More reference expression data
Orthologs
	v; t; e;

　　[★]

英: MAP kinase, mitogen-activated protein kinase, MAPK
同: マイトジェン活性化プロテインキナーゼ、マップキナーゼ
関: MAPキナーゼスーパーファミリーカスケード。mitogen-activated protein

リン酸化部位：スレオニン、チロシン
MAPKKによってスレオニンとチロシン残基がリン酸化される。

MAPKスーパーファミリー

ERK1/ERK2
JNK1/JNK2/JNK3
p38α/p38β/p38γ/p38δ
ERK5

「MAPKスーパーファミリー」

　　[★]

TXY配列を持つ一群のキナーゼの総称

増殖刺激

ERK1/ERK2：非リン酸化配列(TEY)

ストレス応答MAPK：高浸透圧・過酸化水素、熱ショック、タンパク質合成阻害、紫外線、放射線、抗ガン剤、虚血/再灌流・血清除去、LPS、炎症性サイトカイン、TGF-β、Fas

JNK1/JNK2/JNK3：非リン酸化配列(TPY)

p38α/p38β/p38γ/p38δ：非リン酸化配列(TGY)

ERK5：非リン酸化配列(TEY)

「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