細胞外シグナル制御キナーゼ2

関: extracellular signal-regulated kinase 2

Wikipedia preview

出典(authority):フリー百科事典『ウィキペディア（Wikipedia）』「2015/07/01 12:42:24」(JST)

wiki en

Mitogen-activated protein kinase 1, also known as MAPK1, p42MAPK, and ERK2, is an enzyme that in humans is encoded by the MAPK1 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 as an integration point for multiple biochemical signals, and are involved in a wide variety of cellular processes such as proliferation, differentiation, transcription regulation and development. The activation of this kinase requires its phosphorylation by upstream kinases. Upon activation, this kinase translocates to the nucleus of the stimulated cells, where it phosphorylates nuclear targets. Two alternatively spliced transcript variants encoding the same protein, but differing in the UTRs, have been reported for this gene.^[2]

Model organisms

*Mapk1* knockout mouse phenotype
Characteristic	Phenotype
Homozygote viability	Abnormal
Recessive lethal study	Abnormal
Fertility	Normal
Body weight	Normal
Anxiety	Normal
Neurological assessment	Normal
Grip strength	Normal
Hot plate	Normal
Dysmorphology	Normal^[3]
Indirect calorimetry	Normal
Glucose tolerance test	Normal
Auditory brainstem response	Normal
DEXA	Normal
Radiography	Normal
Body temperature	Normal
Eye morphology	Normal
Clinical chemistry	Abnormal^[4]
Plasma immunoglobulins	Normal
Haematology	Normal
Peripheral blood lymphocytes	Normal
Micronucleus test	Normal
Heart weight	Normal
Tail epidermis wholemount	Normal
Skin Histopathology	Normal
Brain histopathology	Normal
Salmonella infection	Normal^[5]
Citrobacter infection	Normal^[6]
All tests and analysis from^[7]^[8]

Model organisms have been used in the study of MAPK1 function. A conditional knockout mouse line, called Mapk1^{tm1a(EUCOMM)Wtsi}^[9]^[10] was generated as part of the International Knockout Mouse Consortium program — a high-throughput mutagenesis project to generate and distribute animal models of disease to interested scientists.^[11]^[12]^[13]

Male and female animals underwent a standardized phenotypic screen to determine the effects of deletion.^[7]^[14] Twenty seven tests were carried out on mutant mice and three significant abnormalities were observed.^[7] No homozygous mutant embryos were identified during gestation, and therefore none survived until weaning. The remaining tests were carried out on heterozygous mutant adult mice and males had decreased circulating amylase levels.^[7]

Interactions

MAPK1 has been shown to interact with:

ADAM17,^[15]
CIITA,^[16]
DUSP1,^[17]^[18]
DUSP22,^[19]
DUSP3,^[20]
ELK1,^[21]^[22]
FHL2,^[23]
HDAC4,^[24]
MAP2K1,^[25]^[26]^[27]^[28]^[29]^[30]
MAP3K1^[31]
MAPK14,^[25]^[32]
MKNK1,^[33]
MKNK2,^[33]^[34]
Myc,^[35]^[36]^[37]
NEK2,^[38]
PEA15,^[39]
PTPN7,^[40]^[41]
Phosphatidylethanolamine binding protein 1,^[27]
RPS6KA1,^[42]^[43]^[21]
RPS6KA2,^[44]^[43]
RPS6KA3,^[44]^[42]
SORBS3,^[45]
STAT5A,^[46]^[47]
TNIP1,^[48]
TOB1,^[49]
TSC2,^[50]
UBR5,^[21] and
VAV1.^[51]^[52]

References

^ Owaki H, Makar R, Boulton TG, Cobb MH, Geppert TD (February 1992). "Extracellular signal-regulated kinases in T cells: characterization of human ERK1 and ERK2 cDNAs". Biochem. Biophys. Res. Commun. 182 (3): 1416–22. doi:10.1016/0006-291X(92)91891-S. PMID 1540184.
^ "Entrez Gene: MAPK1 mitogen-activated protein kinase 1".
^ "Dysmorphology data for Mapk1". Wellcome Trust Sanger Institute.
^ "Clinical chemistry data for Mapk1". Wellcome Trust Sanger Institute.
^ "Salmonella infection data for Mapk1". Wellcome Trust Sanger Institute.
^ "Citrobacter infection data for Mapk1". Wellcome Trust Sanger Institute.
^ ^a ^b ^c ^d Gerdin, AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.
^ Mouse Resources Portal, Wellcome Trust Sanger Institute.
^ "International Knockout Mouse Consortium".
^ "Mouse Genome Informatics".
^ Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V et al. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.
^ Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.
^ Collins FS, Rossant J, Wurst W (2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.
^ van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.
^ Díaz-Rodríguez E, Montero JC, Esparís-Ogando A, Yuste L, Pandiella A (June 2002). "Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated shedding". Mol. Biol. Cell 13 (6): 2031–44. doi:10.1091/mbc.01-11-0561. PMC 117622. PMID 12058067.
^ Voong LN, Slater AR, Kratovac S, Cressman DE (April 2008). "Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator". J. Biol. Chem. 283 (14): 9031–9. doi:10.1074/jbc.M706487200. PMC 2431044. PMID 18245089.
^ Slack DN, Seternes OM, Gabrielsen M, Keyse SM (May 2001). "Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1". J. Biol. Chem. 276 (19): 16491–500. doi:10.1074/jbc.M010966200. PMID 11278799.
^ Calvisi DF, Pinna F, Meloni F, Ladu S, Pellegrino R, Sini M et al. (June 2008). "Dual-specificity phosphatase 1 ubiquitination in extracellular signal-regulated kinase-mediated control of growth in human hepatocellular carcinoma". Cancer Res. 68 (11): 4192–200. doi:10.1158/0008-5472.CAN-07-6157. PMID 18519678.
^ Aoyama K, Nagata M, Oshima K, Matsuda T, Aoki N (July 2001). "Molecular cloning and characterization of a novel dual specificity phosphatase, LMW-DSP2, that lacks the cdc25 homology domain". J. Biol. Chem. 276 (29): 27575–83. doi:10.1074/jbc.M100408200. PMID 11346645.
^ 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.
^ ^a ^b ^c Eblen ST, Kumar NV, Shah K, Henderson MJ, Watts CK, Shokat KM et al. (April 2003). "Identification of novel ERK2 substrates through use of an engineered kinase and ATP analogs". J. Biol. Chem. 278 (17): 14926–35. doi:10.1074/jbc.M300485200. PMID 12594221.
^ Cano E, Hazzalin CA, Kardalinou E, Buckle RS, Mahadevan LC (November 1995). "Neither ERK nor JNK/SAPK MAP kinase subtypes are essential for histone H3/HMG-14 phosphorylation or c-fos and c-jun induction". J. Cell. Sci. 108 (11): 3599–609. PMID 8586671.
^ Purcell NH, Darwis D, Bueno OF, Müller JM, Schüle R, Molkentin JD (February 2004). "Extracellular signal-regulated kinase 2 interacts with and is negatively regulated by the LIM-only protein FHL2 in cardiomyocytes". Mol. Cell. Biol. 24 (3): 1081–95. doi:10.1128/mcb.24.3.1081-1095.2004. PMC 321437. PMID 14729955.
^ 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 Sanz-Moreno V, Casar B, Crespo P (May 2003). "p38alpha 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. 23 (9): 3079–90. doi:10.1128/mcb.23.9.3079-3090.2003. PMC 153192. PMID 12697810.
^ Robinson FL, Whitehurst AW, Raman M, Cobb MH (April 2002). "Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1". J. Biol. Chem. 277 (17): 14844–52. doi:10.1074/jbc.M107776200. PMID 11823456.
^ ^a ^b Yeung K, Janosch P, McFerran B, Rose DW, Mischak H, Sedivy JM et al. (May 2000). "Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein". Mol. Cell. Biol. 20 (9): 3079–85. doi:10.1128/mcb.20.9.3079-3085.2000. PMC 85596. PMID 10757792.
^ Wunderlich W, Fialka I, Teis D, Alpi A, Pfeifer A, Parton RG et al. (February 2001). "A novel 14-kilodalton protein interacts with the mitogen-activated protein kinase scaffold mp1 on a late endosomal/lysosomal compartment". J. Cell Biol. 152 (4): 765–76. doi:10.1083/jcb.152.4.765. PMC 2195784. PMID 11266467.
^ Stippec S, Robinson FL, Cobb MH (July 2001). "Hydrophobic as well as charged residues in both MEK1 and ERK2 are important for their proper docking". J. Biol. Chem. 276 (28): 26509–15. doi:10.1074/jbc.M102769200. PMID 11352917.
^ Chen Z, Cobb MH (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118.
^ Karandikar M, Xu S, Cobb MH (December 2000). "MEKK1 binds raf-1 and the ERK2 cascade components". J. Biol. Chem. 275 (51): 40120–7. doi:10.1074/jbc.M005926200. PMID 10969079.
^ Tanoue T, Maeda R, Adachi M, Nishida E (February 2001). "Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions". EMBO J. 20 (3): 466–79. doi:10.1093/emboj/20.3.466. PMC 133461. PMID 11157753.
^ ^a ^b Waskiewicz AJ, Flynn A, Proud CG, Cooper JA (April 1997). "Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. 16 (8): 1909–20. doi:10.1093/emboj/16.8.1909. PMC 1169794. PMID 9155017.
^ Scheper GC, Parra JL, Wilson M, Van Kollenburg B, Vertegaal AC, Han ZG et al. (August 2003). "The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization". Mol. Cell. Biol. 23 (16): 5692–705. doi:10.1128/mcb.23.16.5692-5705.2003. PMC 166352. PMID 12897141.
^ Jin Z, Gao F, Flagg T, Deng X (September 2004). "Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation". J. Biol. Chem. 279 (38): 40209–19. doi:10.1074/jbc.M404056200. PMID 15210690.
^ Gupta S, Davis RJ (October 1994). "MAP kinase binds to the NH2-terminal activation domain of c-Myc". FEBS Lett. 353 (3): 281–5. doi:10.1016/0014-5793(94)01052-8. PMID 7957875.
^ Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ (July 1997). "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. 94 (14): 7337–42. doi:10.1073/pnas.94.14.7337. PMC 23822. PMID 9207092.
^ Lou Y, Xie W, Zhang DF, Yao JH, Luo ZF, Wang YZ et al. (August 2004). "Nek2A specifies the centrosomal localization of Erk2". Biochem. Biophys. Res. Commun. 321 (2): 495–501. doi:10.1016/j.bbrc.2004.06.171. PMID 15358203.
^ Formstecher E, Ramos JW, Fauquet M, Calderwood DA, Hsieh JC, Canton B et al. (August 2001). "PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase". Dev. Cell 1 (2): 239–50. doi:10.1016/s1534-5807(01)00035-1. PMID 11702783.
^ 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, 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.
^ ^a ^b Smith JA, Poteet-Smith CE, Malarkey K, Sturgill TW (January 1999). "Identification of an extracellular signal-regulated kinase (ERK) docking site in ribosomal S6 kinase, a sequence critical for activation by ERK in vivo". J. Biol. Chem. 274 (5): 2893–8. doi:10.1074/jbc.274.5.2893. PMID 9915826.
^ ^a ^b 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.
^ ^a ^b 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.
^ Mitsushima M, Suwa A, Amachi T, Ueda K, Kioka N (August 2004). "Extracellular signal-regulated kinase activated by epidermal growth factor and cell adhesion interacts with and phosphorylates vinexin". J. Biol. Chem. 279 (33): 34570–7. doi:10.1074/jbc.M402304200. PMID 15184391.
^ Pircher TJ, Petersen H, Gustafsson JA, Haldosén LA (April 1999). "Extracellular signal-regulated kinase (ERK) interacts with signal transducer and activator of transcription (STAT) 5a". Mol. Endocrinol. 13 (4): 555–65. doi:10.1210/mend.13.4.0263. PMID 10194762.
^ Dinerstein-Cali H, Ferrag F, Kayser C, Kelly PA, Postel-Vinay M (August 2000). "Growth hormone (GH) induces the formation of protein complexes involving Stat5, Erk2, Shc and serine phosphorylated proteins". Mol. Cell. Endocrinol. 166 (2): 89–99. doi:10.1016/s0303-7207(00)00277-x. PMID 10996427.
^ Zhang S, Fukushi M, Hashimoto S, Gao C, Huang L, Fukuyo Y et al. (September 2002). "A new ERK2 binding protein, Naf1, attenuates the EGF/ERK2 nuclear signaling". Biochem. Biophys. Res. Commun. 297 (1): 17–23. doi:10.1016/s0006-291x(02)02086-7. PMID 12220502.
^ Maekawa M, Nishida E, Tanoue T (October 2002). "Identification of the Anti-proliferative protein Tob as a MAPK substrate". J. Biol. Chem. 277 (40): 37783–7. doi:10.1074/jbc.M204506200. PMID 12151396.
^ Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP (April 2005). "Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis". Cell 121 (2): 179–93. doi:10.1016/j.cell.2005.02.031. PMID 15851026.
^ Song JS, Gomez J, Stancato LF, Rivera J (October 1996). "Association of a p95 Vav-containing signaling complex with the FcepsilonRI gamma chain in the RBL-2H3 mast cell line. Evidence for a constitutive in vivo association of Vav with Grb2, Raf-1, and ERK2 in an active complex". J. Biol. Chem. 271 (43): 26962–70. doi:10.1074/jbc.271.43.26962. PMID 8900182.
^ Lee IS, Liu Y, Narazaki M, Hibi M, Kishimoto T, Taga T (January 1997). "Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6". FEBS Lett. 401 (2-3): 133–7. doi:10.1016/s0014-5793(96)01456-1. PMID 9013873.

External links

MAP Kinase Resource .

UpToDate Contents

全文を閲覧するには購読必要です。 To read the full text you will need to subscribe.

1. 黒色腫（メラノーマ）の分子生物学 the molecular biology of melanoma
2. 進行性肝細胞癌に対する全身治療 systemic treatment for advanced hepatocellular carcinoma
3. 結節性硬化症：遺伝学、臨床的特徴、および診断 tuberous sclerosis complex genetics clinical features and diagnosis
4. 薬物誘発性ループス drug induced lupus
5. 頭頸部の扁平上皮癌化：分子学的および遺伝学的変化 head and neck squamous cell carcinogenesis molecular and genetic alterations

English Journal

The extra-cellular signal regulated kinases ERK1 and ERK2 segregate displaying distinct spatiotemporal characteristics in activated mast cells.

Bar-Gill AB, Efergan A, Seger R, Fukuda M, Sagi-Eisenberg R.SourceDepartment of Cell and Developmental Biology, Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv 69978, Israel.
Biochimica et biophysica acta.Biochim Biophys Acta.2013 Sep;1832(9):2070-82. doi: 10.1016/j.bbamcr.2013.04.016. Epub 2013 May 5.
ERK1 and ERK2 are highly homologous isoforms that often play redundant roles in regulating cellular functions. We analyzed the spatiotemporal patterns of ERK1 and ERK2 in resting and activated mast cells. Strikingly, we identified distinct pathways for these kinases. ERK1 localized to the cytosol an
PMID 23651922

Convergence of nicotine-induced and auditory-evoked neural activity activates ERK in auditory cortex.

Kawai HD, La M, Kang HA, Hashimoto Y, Liang K, Lazar R, Metherate R.SourceDepartment of Neurobiology and Behavior and Center for Hearing Research, University of California, Irvine, California; Department of Bioinformatics, Faculty of Engineering, Soka University, Hachiouji, Tokyo, Japan.
Synapse (New York, N.Y.).Synapse.2013 Aug;67(8):455-68. doi: 10.1002/syn.21647. Epub 2013 Mar 8.
Enhancement of sound-evoked responses in auditory cortex (ACx) following administration of systemic nicotine is known to depend on activation of extracellular-signaling regulated kinase (ERK), but the nature of this enhancement is not clear. Here, we show that systemic nicotine increases the density
PMID 23401204

Improved N(α)-Acetylated Peptide Enrichment Following Dimethyl Labeling and SCX.

Chen SH, Chen CR, Chen SH, Li DT, Hsu JL.SourceDepartment of Biological Science and Technology, National Pingtung University of Science and Technology , Pingtung, Taiwan.
Journal of proteome research.J Proteome Res.2013 Jul 5;12(7):3277-87. doi: 10.1021/pr400127j. Epub 2013 Jun 19.
Protein N-terminal acetylation is one of the most common modifications occurring co- and post-translationally on either eukaryote or prokaryote proteins. However, compared to other protein modifications, the physiological role of protein N-terminal acetylation is relatively unclear. To explore the b
PMID 23745983

Japanese Journal

腱板断裂におけるメカニカルストレス関連分子の発現

神戸克明,中村篤司,安井謙二
肩関節 35(2), 429-433, 2011
… Phospho-p38 MAPK (Tyr180/Tyr182), phospho-p44/42 MAPK (ERK1/ERK2), phospho-JNK, nuclear factor-kappa B (NF-κB) p50, CD29 (beta-1 integrin), matrix metalloproteinase (MMP)-3, interleukin-6 (IL-6), TNF-α, CD56, CD68, S-100 and the vascular endothelial growth factor (VEGF) were analyzed to detect expression patterns by the methods of Hand et al. …
NAID 130001413719

Activation of Extracellular-Signal Regulated Kinase by Epidermal Growth Factor Is Potentiated by cAMP-Elevating Agents in Primary Cultures of Adult Rat Hepatocytes

Moteki Hajime,Kimura Mitsutoshi,Ogihara Masahiko
Biological & Pharmaceutical Bulletin 34(10), 1542-1552, 2011
… p44 mitogen-activated protein kinase (MAPK) and ERK2; … The results show that EGF induced a 2.5-fold increase in ERK2-, but not ERK1-, phosphorylation within 3 min. This EGF-induced ERK2 activation was abolished by treatment with the EGF-receptor kinase inhibitor AG1478 (10−7 M) or the MEK (MAPK kinase) inhibitor PD98059 (10−6 M). …
NAID 130001086585

Related Pictures

★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」「細胞外シグナル制御キナーゼ2」「extracellular signal-regulated kinase 2」
関連記事	「ERK」「ER」

「MAPキナーゼ」

Mitogen-activated protein kinase 1
	PDB rendering based on 1erk.
Available structures
PDB	Ortholog search: PDBe, RCSB
List of PDB id codes
	1PME, 1TVO, 1WZY, 2OJG, 2OJI, 2OJJ, 2Y9Q, 3D42, 3D44, 3I5Z, 3I60, 3SA0, 3TEI, 3W55, 4FMQ, 4FUX, 4FUY, 4FV0, 4FV1, 4FV2, 4FV3, 4FV4, 4FV5, 4FV6, 4FV7, 4FV8, 4FV9, 4G6N, 4G6O, 4H3P, 4H3Q, 4IZ5, 4IZ7, 4IZA, 4O6E
Identifiers
Symbols	MAPK1 ; ERK; ERK-2; ERK2; ERT1; MAPK2; P42MAPK; PRKM1; PRKM2; p38; p40; p41; p41mapk; p42-MAPK
External IDs	OMIM: 176948 MGI: 1346858 HomoloGene: 37670 IUPHAR: 1495 ChEMBL: 4040 GeneCards: MAPK1 Gene
EC number	2.7.11.24
Gene ontology
Molecular function	• phosphotyrosine binding; • DNA binding; • protein serine/threonine kinase activity; • MAP kinase activity; • protein binding; • ATP binding; • transcription factor binding; • RNA polymerase II carboxy-terminal domain kinase activity; • phosphatase binding; • mitogen-activated protein kinase kinase kinase binding;
Cellular component	• nucleus; • nucleoplasm; • nucleolus; • cytoplasm; • mitochondrion; • early endosome; • late endosome; • Golgi apparatus; • microtubule organizing center; • cytosol; • cytoskeleton; • caveola; • focal adhesion; • microtubule cytoskeleton; • pseudopodium; • dendrite cytoplasm; • perikaryon; • protein complex; • extracellular vesicular exosome; • mitotic spindle;
Biological process	• MAPK cascade; • activation of MAPKK activity; • activation of MAPK activity; • MAPK import into nucleus; • toll-like receptor signaling pathway; • MyD88-dependent toll-like receptor signaling pathway; • MyD88-independent toll-like receptor signaling pathway; • transcription, DNA-templated; • apoptotic process; • chemotaxis; • response to stress; • cellular response to DNA damage stimulus; • cell cycle; • signal transduction; • epidermal growth factor receptor signaling pathway; • small GTPase mediated signal transduction; • Ras protein signal transduction; • synaptic transmission; • axon guidance; • blood coagulation; • positive regulation of cell proliferation; • insulin receptor signaling pathway; • fibroblast growth factor receptor signaling pathway; • response to toxic substance; • organ morphogenesis; • positive regulation of peptidyl-threonine phosphorylation; • viral process; • peptidyl-serine phosphorylation; • peptidyl-threonine phosphorylation; • sensory perception of pain; • cytosine metabolic process; • platelet activation; • positive regulation of cell migration; • regulation of protein stability; • lipopolysaccharide-mediated signaling pathway; • regulation of stress-activated MAPK cascade; • mammary gland epithelial cell proliferation; • 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; • Fc-gamma receptor signaling pathway involved in phagocytosis; • toll-like receptor TLR1:TLR2 signaling pathway; • toll-like receptor TLR6:TLR2 signaling pathway; • ERBB signaling pathway; • response to exogenous dsRNA; • response to estrogen; • innate immune response; • negative regulation of cell differentiation; • positive regulation of translation; • positive regulation of transcription, DNA-templated; • neurotrophin TRK receptor signaling pathway; • T cell receptor signaling pathway; • B cell receptor signaling pathway; • regulation of sequence-specific DNA binding transcription factor activity; • stress-activated MAPK cascade; • regulation of cytoskeleton organization; • JAK-STAT cascade involved in growth hormone signaling pathway; • labyrinthine layer blood vessel development; • ERK1 and ERK2 cascade; • response to epidermal growth factor; • caveolin-mediated endocytosis; • regulation of Golgi inheritance; • regulation of early endosome to late endosome transport;
	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

「細胞外シグナル制御キナーゼ2」

　　[★]

英: extracellular signal-regulated kinase 2、ERK2
関: マイトジェン活性化プロテインキナーゼ1

「extracellular signal-regulated kinase 2」

　　[★]

細胞外シグナル制御キナーゼ2

関: ERK2、mitogen-activated protein kinase 1

「ERK」

　　[★]

同: [[]] extracellular-signal-regulated kinase
関: MAPキナーゼスーパーファミリーカスケード

MAPKファミリーに含まれるERKファミリーを構成
キナーゼサブドメインVIIIの活性化ループに存在するリン酸化部位の配列がTEY
セリンスレオニンキナーゼ
MAPKKであるMEK1,MEK2によってスレオニンとチロシン残基がリン酸化され、活性化される。
ERK1/2の基質

転写因子：Elk-1, Ets1, Sapla, STAT
キナーゼ：p90rsk(p90 ribosomal S6 kinase), MNK1/MNK2
cPLA2
EGF受容体
Sos
細胞骨格構成タンパク質(Map2, Tau)

ERK1
ERK2

同: extracellular-signal-regulated kinase

「ER」

　　[★]

[pmid1540184-1] Owaki H, Makar R, Boulton TG, Cobb MH, Geppert TD (February 1992). "Extracellular signal-regulated kinases in T cells: characterization of human ERK1 and ERK2 cDNAs". Biochem. Biophys. Res. Commun. 182 (3): 1416–22. doi:10.1016/0006-291X(92)91891-S. PMID 1540184.

[2] "Entrez Gene: MAPK1 mitogen-activated protein kinase 1".

[Dysmorphology-3] "Dysmorphology data for Mapk1". Wellcome Trust Sanger Institute.

[Clinical_chemistry-4] "Clinical chemistry data for Mapk1". Wellcome Trust Sanger Institute.

[.27.27Salmonella.27.27_infection-5] "Salmonella infection data for Mapk1". Wellcome Trust Sanger Institute.

[.27.27Citrobacter.27.27_infection-6] "Citrobacter infection data for Mapk1". Wellcome Trust Sanger Institute.

[mgp_reference-7] Gerdin, AK (2010). "The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice". Acta Ophthalmologica 88: 925–7. doi:10.1111/j.1755-3768.2010.4142.x.

[8] Mouse Resources Portal, Wellcome Trust Sanger Institute.

[allele_ref-9] "International Knockout Mouse Consortium".

[mgi_allele_ref-10] "Mouse Genome Informatics".

[pmid21677750-11] Skarnes WC, Rosen B, West AP, Koutsourakis M, Bushell W, Iyer V et al. (2011). "A conditional knockout resource for the genome-wide study of mouse gene function". Nature 474 (7351): 337–42. doi:10.1038/nature10163. PMC 3572410. PMID 21677750.

[mouse_library-12] Dolgin E (2011). "Mouse library set to be knockout". Nature 474 (7351): 262–3. doi:10.1038/474262a. PMID 21677718.

[mouse_for_all_reasons-13] Collins FS, Rossant J, Wurst W (2007). "A mouse for all reasons". Cell 128 (1): 9–13. doi:10.1016/j.cell.2006.12.018. PMID 17218247.

[pmid21722353-14] van der Weyden L, White JK, Adams DJ, Logan DW (2011). "The mouse genetics toolkit: revealing function and mechanism". Genome Biol. 12 (6): 224. doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353.

[pmid12058067-15] Díaz-Rodríguez E, Montero JC, Esparís-Ogando A, Yuste L, Pandiella A (June 2002). "Extracellular signal-regulated kinase phosphorylates tumor necrosis factor alpha-converting enzyme at threonine 735: a potential role in regulated shedding". Mol. Biol. Cell 13 (6): 2031–44. doi:10.1091/mbc.01-11-0561. PMC 117622. PMID 12058067.

[pmid18245089-16] Voong LN, Slater AR, Kratovac S, Cressman DE (April 2008). "Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator". J. Biol. Chem. 283 (14): 9031–9. doi:10.1074/jbc.M706487200. PMC 2431044. PMID 18245089.

[pmid11278799-17] Slack DN, Seternes OM, Gabrielsen M, Keyse SM (May 2001). "Distinct binding determinants for ERK2/p38alpha and JNK map kinases mediate catalytic activation and substrate selectivity of map kinase phosphatase-1". J. Biol. Chem. 276 (19): 16491–500. doi:10.1074/jbc.M010966200. PMID 11278799.

[pmid18519678-18] Calvisi DF, Pinna F, Meloni F, Ladu S, Pellegrino R, Sini M et al. (June 2008). "Dual-specificity phosphatase 1 ubiquitination in extracellular signal-regulated kinase-mediated control of growth in human hepatocellular carcinoma". Cancer Res. 68 (11): 4192–200. doi:10.1158/0008-5472.CAN-07-6157. PMID 18519678.

[pmid11346645-19] Aoyama K, Nagata M, Oshima K, Matsuda T, Aoki N (July 2001). "Molecular cloning and characterization of a novel dual specificity phosphatase, LMW-DSP2, that lacks the cdc25 homology domain". J. Biol. Chem. 276 (29): 27575–83. doi:10.1074/jbc.M100408200. PMID 11346645.

[pmid10224087-20] 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.

[pmid12594221-21] Eblen ST, Kumar NV, Shah K, Henderson MJ, Watts CK, Shokat KM et al. (April 2003). "Identification of novel ERK2 substrates through use of an engineered kinase and ATP analogs". J. Biol. Chem. 278 (17): 14926–35. doi:10.1074/jbc.M300485200. PMID 12594221.

[pmid8586671-22] Cano E, Hazzalin CA, Kardalinou E, Buckle RS, Mahadevan LC (November 1995). "Neither ERK nor JNK/SAPK MAP kinase subtypes are essential for histone H3/HMG-14 phosphorylation or c-fos and c-jun induction". J. Cell. Sci. 108 (11): 3599–609. PMID 8586671.

[pmid14729955-23] Purcell NH, Darwis D, Bueno OF, Müller JM, Schüle R, Molkentin JD (February 2004). "Extracellular signal-regulated kinase 2 interacts with and is negatively regulated by the LIM-only protein FHL2 in cardiomyocytes". Mol. Cell. Biol. 24 (3): 1081–95. doi:10.1128/mcb.24.3.1081-1095.2004. PMC 321437. PMID 14729955.

[pmid11114188-24] 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.

[pmid12697810-25] Sanz-Moreno V, Casar B, Crespo P (May 2003). "p38alpha 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. 23 (9): 3079–90. doi:10.1128/mcb.23.9.3079-3090.2003. PMC 153192. PMID 12697810.

[pmid11823456-26] Robinson FL, Whitehurst AW, Raman M, Cobb MH (April 2002). "Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1". J. Biol. Chem. 277 (17): 14844–52. doi:10.1074/jbc.M107776200. PMID 11823456.

[pmid10757792-27] Yeung K, Janosch P, McFerran B, Rose DW, Mischak H, Sedivy JM et al. (May 2000). "Mechanism of suppression of the Raf/MEK/extracellular signal-regulated kinase pathway by the raf kinase inhibitor protein". Mol. Cell. Biol. 20 (9): 3079–85. doi:10.1128/mcb.20.9.3079-3085.2000. PMC 85596. PMID 10757792.

[pmid11266467-28] Wunderlich W, Fialka I, Teis D, Alpi A, Pfeifer A, Parton RG et al. (February 2001). "A novel 14-kilodalton protein interacts with the mitogen-activated protein kinase scaffold mp1 on a late endosomal/lysosomal compartment". J. Cell Biol. 152 (4): 765–76. doi:10.1083/jcb.152.4.765. PMC 2195784. PMID 11266467.

[pmid11352917-29] Stippec S, Robinson FL, Cobb MH (July 2001). "Hydrophobic as well as charged residues in both MEK1 and ERK2 are important for their proper docking". J. Biol. Chem. 276 (28): 26509–15. doi:10.1074/jbc.M102769200. PMID 11352917.

[pmid11279118-30] Chen Z, Cobb MH (May 2001). "Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2". J. Biol. Chem. 276 (19): 16070–5. doi:10.1074/jbc.M100681200. PMID 11279118.

[pmid10969079-31] Karandikar M, Xu S, Cobb MH (December 2000). "MEKK1 binds raf-1 and the ERK2 cascade components". J. Biol. Chem. 275 (51): 40120–7. doi:10.1074/jbc.M005926200. PMID 10969079.

[pmid11157753-32] Tanoue T, Maeda R, Adachi M, Nishida E (February 2001). "Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions". EMBO J. 20 (3): 466–79. doi:10.1093/emboj/20.3.466. PMC 133461. PMID 11157753.

[pmid9155017-33] Waskiewicz AJ, Flynn A, Proud CG, Cooper JA (April 1997). "Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2". EMBO J. 16 (8): 1909–20. doi:10.1093/emboj/16.8.1909. PMC 1169794. PMID 9155017.

[pmid12897141-34] Scheper GC, Parra JL, Wilson M, Van Kollenburg B, Vertegaal AC, Han ZG et al. (August 2003). "The N and C termini of the splice variants of the human mitogen-activated protein kinase-interacting kinase Mnk2 determine activity and localization". Mol. Cell. Biol. 23 (16): 5692–705. doi:10.1128/mcb.23.16.5692-5705.2003. PMC 166352. PMID 12897141.

[pmid15210690-35] Jin Z, Gao F, Flagg T, Deng X (September 2004). "Tobacco-specific nitrosamine 4-(methylnitrosamino)-1-(3-pyridyl)-1-butanone promotes functional cooperation of Bcl2 and c-Myc through phosphorylation in regulating cell survival and proliferation". J. Biol. Chem. 279 (38): 40209–19. doi:10.1074/jbc.M404056200. PMID 15210690.

[pmid7957875-36] Gupta S, Davis RJ (October 1994). "MAP kinase binds to the NH2-terminal activation domain of c-Myc". FEBS Lett. 353 (3): 281–5. doi:10.1016/0014-5793(94)01052-8. PMID 7957875.

[pmid9207092-37] Tournier C, Whitmarsh AJ, Cavanagh J, Barrett T, Davis RJ (July 1997). "Mitogen-activated protein kinase kinase 7 is an activator of the c-Jun NH2-terminal kinase". Proc. Natl. Acad. Sci. U.S.A. 94 (14): 7337–42. doi:10.1073/pnas.94.14.7337. PMC 23822. PMID 9207092.

[pmid15358203-38] Lou Y, Xie W, Zhang DF, Yao JH, Luo ZF, Wang YZ et al. (August 2004). "Nek2A specifies the centrosomal localization of Erk2". Biochem. Biophys. Res. Commun. 321 (2): 495–501. doi:10.1016/j.bbrc.2004.06.171. PMID 15358203.

[pmid11702783-39] Formstecher E, Ramos JW, Fauquet M, Calderwood DA, Hsieh JC, Canton B et al. (August 2001). "PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase". Dev. Cell 1 (2): 239–50. doi:10.1016/s1534-5807(01)00035-1. PMID 11702783.

[pmid10702794-40] 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.

[pmid10206983-41] 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.

[pmid9915826-42] Smith JA, Poteet-Smith CE, Malarkey K, Sturgill TW (January 1999). "Identification of an extracellular signal-regulated kinase (ERK) docking site in ribosomal S6 kinase, a sequence critical for activation by ERK in vivo". J. Biol. Chem. 274 (5): 2893–8. doi:10.1074/jbc.274.5.2893. PMID 9915826.

[pmid12832467-43] 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.

[pmid8939914-44] 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.

[pmid15184391-45] Mitsushima M, Suwa A, Amachi T, Ueda K, Kioka N (August 2004). "Extracellular signal-regulated kinase activated by epidermal growth factor and cell adhesion interacts with and phosphorylates vinexin". J. Biol. Chem. 279 (33): 34570–7. doi:10.1074/jbc.M402304200. PMID 15184391.

[pmid10194762-46] Pircher TJ, Petersen H, Gustafsson JA, Haldosén LA (April 1999). "Extracellular signal-regulated kinase (ERK) interacts with signal transducer and activator of transcription (STAT) 5a". Mol. Endocrinol. 13 (4): 555–65. doi:10.1210/mend.13.4.0263. PMID 10194762.

[pmid10996427-47] Dinerstein-Cali H, Ferrag F, Kayser C, Kelly PA, Postel-Vinay M (August 2000). "Growth hormone (GH) induces the formation of protein complexes involving Stat5, Erk2, Shc and serine phosphorylated proteins". Mol. Cell. Endocrinol. 166 (2): 89–99. doi:10.1016/s0303-7207(00)00277-x. PMID 10996427.

[pmid12220502-48] Zhang S, Fukushi M, Hashimoto S, Gao C, Huang L, Fukuyo Y et al. (September 2002). "A new ERK2 binding protein, Naf1, attenuates the EGF/ERK2 nuclear signaling". Biochem. Biophys. Res. Commun. 297 (1): 17–23. doi:10.1016/s0006-291x(02)02086-7. PMID 12220502.

[pmid12151396-49] Maekawa M, Nishida E, Tanoue T (October 2002). "Identification of the Anti-proliferative protein Tob as a MAPK substrate". J. Biol. Chem. 277 (40): 37783–7. doi:10.1074/jbc.M204506200. PMID 12151396.

[pmid15851026-50] Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP (April 2005). "Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis". Cell 121 (2): 179–93. doi:10.1016/j.cell.2005.02.031. PMID 15851026.

[pmid8900182-51] Song JS, Gomez J, Stancato LF, Rivera J (October 1996). "Association of a p95 Vav-containing signaling complex with the FcepsilonRI gamma chain in the RBL-2H3 mast cell line. Evidence for a constitutive in vivo association of Vav with Grb2, Raf-1, and ERK2 in an active complex". J. Biol. Chem. 271 (43): 26962–70. doi:10.1074/jbc.271.43.26962. PMID 8900182.

[pmid9013873-52] Lee IS, Liu Y, Narazaki M, Hibi M, Kishimoto T, Taga T (January 1997). "Vav is associated with signal transducing molecules gp130, Grb2 and Erk2, and is tyrosine phosphorylated in response to interleukin-6". FEBS Lett. 401 (2-3): 133–7. doi:10.1016/s0014-5793(96)01456-1. PMID 9013873.

匿名

検索

案内

案内

ERK2