MAPK1
MAPK1 | |||||||||||||||||||||||||
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記号 | MAPK1, ERK, ERK-2, ERK2, ERT1, MAPK2, P42MAPK, PRKM1, PRKM2, p38, p40, p41, p41mapk, p42-MAPK, mitogen-activated protein kinase 1, NS13 | ||||||||||||||||||||||||
外部ID | OMIM: 176948 MGI: 1346858 HomoloGene: 37670 GeneCards: MAPK1 | ||||||||||||||||||||||||
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オルソログ | |||||||||||||||||||||||||
種 | ヒト | マウス | |||||||||||||||||||||||
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Ensembl |
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RefSeq (タンパク質) |
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場所 (UCSC) | Chr 22: 21.76 – 21.87 Mb | Chr 22: 16.8 – 16.87 Mb | |||||||||||||||||||||||
PubMed検索 | [3] | [4] | |||||||||||||||||||||||
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MAPK1(mitogen-activated protein kinase 1)またはERK2(extracellular signal-regulated kinase 2)は、ヒトではMAPK1遺伝子にコードされる酵素(プロテインキナーゼ)である[5]。
機能
MAPK1はMAPキナーゼファミリーの一員である。ERK(extracellular signal-regulated kinase)としても知られるMAPキナーゼは、複数の生化学的シグナルの統合点として作用しており、細胞増殖、分化、転写調節、発生など幅広い細胞過程に関与している。このキナーゼの活性化には、上流のキナーゼによるリン酸化が必要である。活性化に伴って、このキナーゼは刺激された細胞の核内へ移行し、そこで核内の標的をリン酸化する。MAPK1遺伝子には、同一のタンパク質をコードするもののUTRが異なる、2種類の選択的スプライシングバリアントが報告されている[6]。MAPK1には複数のリン酸化部位やユビキチン化部位が存在する[7]。
モデル生物
MAPK1の機能の研究にはモデル生物が広く利用されている。疾患の動物モデルを作製して関心のある科学者に頒布するハイスループット変異体作製プロジェクトである国際ノックアウトマウスコンソーシアム(英語版)プログラムの一環として、Mapk1tm1a(EUCOMM)Wtsi[8][9]と呼ばれるコンディショナルノックアウトマウスが作製されている[10][11][12]。
オスとメスのマウスに対し、遺伝子欠失の影響を調べるための規格化された表現型スクリーニングが行われている[13][14]。変異体マウスに対して27種類の試験が行われており、3つの重大な異常が観察されている[13]。妊娠中にホモ接合型変異体の胚は観察されず、そのため離乳期まで生存した個体はなかった。その他の試験はヘテロ接合型変異体の成体マウスに対して行われ、オスでは血中アミラーゼ濃度の低下が観察された[13]。
B細胞でのMapk1のコンディショナル欠失によって、MAPK1がT細胞依存的な抗体産生に関与していることが示されている[15]。Mapk1に優性機能獲得型変異を有するトランスジェニックマウスでは、MAPK1がT細胞の発生に関与していることが示されている[16]。発生中の大脳皮質の神経前駆細胞におけるMapk1のコンディショナル不活性化は、皮質の厚さの減少と神経前駆細胞の増殖の低下をもたらす[17]。
相互作用
MAPK1は次に挙げる因子と相互作用することが示されている。
- ADAM17(英語版)[18]
- CIITA(英語版)[19]
- DUSP1(英語版)[20][21]
- DUSP22(英語版)[22]
- DUSP3(英語版)[23]
- ELK1(英語版)[24][25]
- FHL2(英語版)[26]
- HDAC4(英語版)[27]
- MAP2K1[28][29][30][31][32][33]
- MAP3K1(英語版)[34]
- MAPK14(英語版)[28][35]
- MKNK1(英語版)[36]
- MKNK2(英語版)[36][37]
- Myc[38][39][40]
- NEK2(英語版)[41]
- PEA15(英語版)[42]
- PTPN7(英語版)[43][44]
- PEBP1(英語版)[30]
- RPS6KA1(英語版)[24][45][46]
- RPS6KA2(英語版)[46][47]
- RPS6KA3(英語版)[45][47]
- SORBS3(英語版)[48]
- STAT5A(英語版)[49][50]
- TNIP1(英語版)[51]
- TOB1(英語版)[52]
- TSC2[53]
- UBR5(英語版)[24]
- VAV1(英語版)[54][55]
臨床的意義
MAPK1の変異は多くの種類のがんへの関与が示唆されている[56]。
出典
- ^ a b c GRCh38: Ensembl release 89: ENSG00000100030 - Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000063358 - Ensembl, May 2017
- ^ Human PubMed Reference:
- ^ Mouse PubMed Reference:
- ^ “Extracellular signal-regulated kinases in T cells: characterization of human ERK1 and ERK2 cDNAs”. Biochem. Biophys. Res. Commun. 182 (3): 1416–22. (February 1992). doi:10.1016/0006-291X(92)91891-S. PMID 1540184.
- ^ “Entrez Gene: MAPK1 mitogen-activated protein kinase 1”. 2023年7月17日閲覧。
- ^ “ERK2 (human)”. www.phosphosite.org. 2020年10月31日閲覧。
- ^ “Mapk1 Mouse Gene Details | mitogen-activated protein kinase 1 | International Mouse Phenotyping Consortium” (英語). www.mousephenotype.org. 2023年7月17日閲覧。
- ^ “Mapk1 Targeted Allele Detail MGI Mouse (MGI:4432537)”. www.informatics.jax.org. 2023年7月17日閲覧。
- ^ “A conditional knockout resource for the genome-wide study of mouse gene function”. Nature 474 (7351): 337–42. (2011). doi:10.1038/nature10163. PMC 3572410. PMID 21677750. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3572410/.
- ^ “Mouse library set to be knockout”. Nature 474 (7351): 262–3. (2011). doi:10.1038/474262a. PMID 21677718.
- ^ “A mouse for all reasons”. Cell 128 (1): 9–13. (2007). doi:10.1016/j.cell.2006.12.018. PMID 17218247.
- ^ a b c “The Sanger Mouse Genetics Programme: High throughput characterisation of knockout mice”. Acta Ophthalmologica 88: 925–7. (2010). doi:10.1111/j.1755-3768.2010.4142.x.
- ^ “The mouse genetics toolkit: revealing function and mechanism”. Genome Biol. 12 (6): 224. (2011). doi:10.1186/gb-2011-12-6-224. PMC 3218837. PMID 21722353. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3218837/.
- ^ “Extracellular signal-regulated protein kinase 2 is required for efficient generation of B cells bearing antigen-specific immunoglobulin G”. Molecular and Cellular Biology 27 (4): 1236–46. (February 2007). doi:10.1128/MCB.01530-06. PMC 1800707. PMID 17145771. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1800707/.
- ^ “The influence of the MAPK pathway on T cell lineage commitment”. Immunity 7 (5): 609–18. (November 1997). doi:10.1016/s1074-7613(00)80382-9. PMID 9390685.
- ^ “Deletion of ERK2 mitogen-activated protein kinase identifies its key roles in cortical neurogenesis and cognitive function”. The Journal of Neuroscience 28 (27): 6983–95. (July 2008). doi:10.1523/JNEUROSCI.0679-08.2008. PMC 4364995. PMID 18596172. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4364995/.
- ^ “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. (June 2002). doi:10.1091/mbc.01-11-0561. PMC 117622. PMID 12058067. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC117622/.
- ^ “Mitogen-activated protein kinase ERK1/2 regulates the class II transactivator”. J. Biol. Chem. 283 (14): 9031–9. (April 2008). doi:10.1074/jbc.M706487200. PMC 2431044. PMID 18245089. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2431044/.
- ^ “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. (May 2001). doi:10.1074/jbc.M010966200. PMID 11278799.
- ^ “Dual-specificity phosphatase 1 ubiquitination in extracellular signal-regulated kinase-mediated control of growth in human hepatocellular carcinoma”. Cancer Res. 68 (11): 4192–200. (June 2008). doi:10.1158/0008-5472.CAN-07-6157. PMID 18519678.
- ^ “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. (July 2001). doi:10.1074/jbc.M100408200. PMID 11346645.
- ^ “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. (May 1999). doi:10.1074/jbc.274.19.13271. PMID 10224087.
- ^ a b c “Identification of novel ERK2 substrates through use of an engineered kinase and ATP analogs”. J. Biol. Chem. 278 (17): 14926–35. (April 2003). doi:10.1074/jbc.M300485200. PMID 12594221.
- ^ “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. (November 1995). doi:10.1242/jcs.108.11.3599. PMID 8586671.
- ^ “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. (February 2004). doi:10.1128/mcb.24.3.1081-1095.2004. PMC 321437. PMID 14729955. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC321437/.
- ^ “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. (December 2000). Bibcode: 2000PNAS...9714329Z. doi:10.1073/pnas.250494697. PMC 18918. PMID 11114188. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC18918/.
- ^ a b “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. (May 2003). doi:10.1128/mcb.23.9.3079-3090.2003. PMC 153192. PMID 12697810. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC153192/.
- ^ “Identification of novel point mutations in ERK2 that selectively disrupt binding to MEK1”. J. Biol. Chem. 277 (17): 14844–52. (April 2002). doi:10.1074/jbc.M107776200. PMID 11823456.
- ^ a b “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. (May 2000). doi:10.1128/mcb.20.9.3079-3085.2000. PMC 85596. PMID 10757792. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC85596/.
- ^ “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. (February 2001). doi:10.1083/jcb.152.4.765. PMC 2195784. PMID 11266467. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2195784/.
- ^ “Hydrophobic as well as charged residues in both MEK1 and ERK2 are important for their proper docking”. J. Biol. Chem. 276 (28): 26509–15. (July 2001). doi:10.1074/jbc.M102769200. PMID 11352917.
- ^ “Regulation of stress-responsive mitogen-activated protein (MAP) kinase pathways by TAO2”. J. Biol. Chem. 276 (19): 16070–5. (May 2001). doi:10.1074/jbc.M100681200. PMID 11279118.
- ^ “MEKK1 binds raf-1 and the ERK2 cascade components”. J. Biol. Chem. 275 (51): 40120–7. (December 2000). doi:10.1074/jbc.M005926200. PMID 10969079.
- ^ “Identification of a docking groove on ERK and p38 MAP kinases that regulates the specificity of docking interactions”. EMBO J. 20 (3): 466–79. (February 2001). doi:10.1093/emboj/20.3.466. PMC 133461. PMID 11157753. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC133461/.
- ^ a b “Mitogen-activated protein kinases activate the serine/threonine kinases Mnk1 and Mnk2”. EMBO J. 16 (8): 1909–20. (April 1997). doi:10.1093/emboj/16.8.1909. PMC 1169794. PMID 9155017. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC1169794/.
- ^ “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. (August 2003). doi:10.1128/mcb.23.16.5692-5705.2003. PMC 166352. PMID 12897141. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC166352/.
- ^ “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. (September 2004). doi:10.1074/jbc.M404056200. PMID 15210690.
- ^ “MAP kinase binds to the NH2-terminal activation domain of c-Myc”. FEBS Lett. 353 (3): 281–5. (October 1994). doi:10.1016/0014-5793(94)01052-8. PMID 7957875.
- ^ “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. (July 1997). Bibcode: 1997PNAS...94.7337T. doi:10.1073/pnas.94.14.7337. PMC 23822. PMID 9207092. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC23822/.
- ^ “Nek2A specifies the centrosomal localization of Erk2”. Biochem. Biophys. Res. Commun. 321 (2): 495–501. (August 2004). doi:10.1016/j.bbrc.2004.06.171. PMID 15358203.
- ^ “PEA-15 mediates cytoplasmic sequestration of ERK MAP kinase”. Dev. Cell 1 (2): 239–50. (August 2001). doi:10.1016/s1534-5807(01)00035-1. PMID 11702783.
- ^ “The MAP-kinase ERK2 is a specific substrate of the protein tyrosine phosphatase HePTP”. Oncogene 19 (7): 858–69. (February 2000). doi:10.1038/sj.onc.1203408. PMID 10702794.
- ^ “Inhibition of T cell signaling by mitogen-activated protein kinase-targeted hematopoietic tyrosine phosphatase (HePTP)”. J. Biol. Chem. 274 (17): 11693–700. (April 1999). doi:10.1074/jbc.274.17.11693. PMID 10206983.
- ^ a b “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. (January 1999). doi:10.1074/jbc.274.5.2893. PMID 9915826.
- ^ a b “Phosphorylation of p90 ribosomal S6 kinase (RSK) regulates extracellular signal-regulated kinase docking and RSK activity”. Mol. Cell. Biol. 23 (14): 4796–804. (July 2003). doi:10.1128/mcb.23.14.4796-4804.2003. PMC 162206. PMID 12832467. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC162206/.
- ^ a b “Regulation and interaction of pp90(rsk) isoforms with mitogen-activated protein kinases”. J. Biol. Chem. 271 (47): 29773–9. (November 1996). doi:10.1074/jbc.271.47.29773. PMID 8939914.
- ^ “Extracellular signal-regulated kinase activated by epidermal growth factor and cell adhesion interacts with and phosphorylates vinexin”. J. Biol. Chem. 279 (33): 34570–7. (August 2004). doi:10.1074/jbc.M402304200. PMID 15184391.
- ^ “Extracellular signal-regulated kinase (ERK) interacts with signal transducer and activator of transcription (STAT) 5a”. Mol. Endocrinol. 13 (4): 555–65. (April 1999). doi:10.1210/mend.13.4.0263. PMID 10194762.
- ^ “Growth hormone (GH) induces the formation of protein complexes involving Stat5, Erk2, Shc and serine phosphorylated proteins”. Mol. Cell. Endocrinol. 166 (2): 89–99. (August 2000). doi:10.1016/s0303-7207(00)00277-x. PMID 10996427.
- ^ “A new ERK2 binding protein, Naf1, attenuates the EGF/ERK2 nuclear signaling”. Biochem. Biophys. Res. Commun. 297 (1): 17–23. (September 2002). doi:10.1016/s0006-291x(02)02086-7. PMID 12220502.
- ^ “Identification of the Anti-proliferative protein Tob as a MAPK substrate”. J. Biol. Chem. 277 (40): 37783–7. (October 2002). doi:10.1074/jbc.M204506200. PMID 12151396.
- ^ “Phosphorylation and functional inactivation of TSC2 by Erk implications for tuberous sclerosis and cancer pathogenesis”. Cell 121 (2): 179–93. (April 2005). doi:10.1016/j.cell.2005.02.031. PMID 15851026.
- ^ “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. (October 1996). doi:10.1074/jbc.271.43.26962. PMID 8900182.
- ^ “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. (January 1997). doi:10.1016/s0014-5793(96)01456-1. PMID 9013873.
- ^ “Expression of MAPK1 in cancer - Summary - The Human Protein Atlas”. www.proteinatlas.org. 2023年7月17日閲覧。
関連文献
- “Hyperphosphorylation of tau in PHF”. Neurobiol. Aging 16 (3): 365–71; discussion 371–80. (1995). doi:10.1016/0197-4580(95)00027-C. PMID 7566346.
- “Histone deacetylase isoforms regulate innate immune responses by deacetylating mitogen-activated protein kinase phosphatase-1”. J Leukoc Biol 95 (4): 651–9. (2014). doi:10.1189/jlb.1013565. PMID 24374966.
- “Transcriptional regulation by MAP kinases”. Mol. Reprod. Dev. 42 (4): 459–67. (1995). doi:10.1002/mrd.1080420414. PMID 8607977.
- “Tat-induced deregulation of neuronal differentiation and survival by nerve growth factor pathway”. J. Neurovirol. 8 Suppl 2 (2): 91–6. (2002). doi:10.1080/13550280290167885. PMID 12491158.
- “HIV-1 Nef control of cell signalling molecules: multiple strategies to promote virus replication”. J. Biosci. 28 (3): 323–35. (2003). doi:10.1007/BF02970151. PMID 12734410.
- “The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition”. Oncogene 26 (22): 3227–39. (2007). doi:10.1038/sj.onc.1210414. PMID 17496918.
関連項目
外部リンク
- MAP Kinase Resource Archived 2021-04-15 at the Wayback Machine.