MAPK3

MAPK3
Доступные структуры
PDB	Поиск ортологов: PDBe RCSB
List of PDB id codes
	2ZOQ, 4QTB
Идентификаторы
Символы	MAPK3, ERK-1, ERK1, ERT2, HS44KDAP, HUMKER1A, P44ERK1, P44MAPK, PRKM3, p44-ERK1, p44-MAPK, mitogen-activated protein kinase 3
Внешние IDs	OMIM: 601795 MGI: 1346859 HomoloGene: 55682 GeneCards: MAPK3
Расположение гена (человек)
Хр.	16-я хромосома человека
Конец	30,123,506 bp
Расположение гена (мышь)
Хр.	Chromosome 7 (mouse)
Конец	126,364,991 bp
Паттерн экспрессии РНК
	Top expressed in
	Цитоархитектоническое поле Бродмана 9;
	Top expressed in
	pyloric antrum; ; Epithelium of stomach;
	More reference expression data
	More reference expression data
Генная онтология
Функции	phosphatase binding; АТФ-связанные; protein kinase activity; MAP kinase activity; трансферазная активность; phosphotyrosine residue binding; scaffold protein binding; связывание с белками плазмы; нуклеотид-связывающий; kinase activity; protein serine/threonine kinase activity; MAP kinase kinase activity; связывание похожих белков;
Компонент клетки	цитозоль; ядерная оболочка; Фокальные контакты; митохондрия; Цитоскелет; клеточное ядро; late endosome; аппарат Гольджи; early endosome; Псевдоподия; нуклеоплазма; цитоплазма; клеточная мембрана; Кавеола; мембрана; protein-containing complex;
Биологический процесс	caveolin-mediated endocytosis; positive regulation of protein phosphorylation; positive regulation of telomere capping; response to exogenous dsRNA; cardiac neural crest cell development involved in heart development; positive regulation of xenophagy; positive regulation of translation; cellular response to DNA damage stimulus; platelet activation; Fc-epsilon receptor signaling pathway; фосфорилация белка; cellular response to mechanical stimulus; face development; positive regulation of histone modification; regulation of DNA-binding transcription factor activity; DNA damage induced protein phosphorylation; positive regulation of ERK1 and ERK2 cascade; морфогенез органа животных; клеточный цикл; апоптоз; Fc-gamma receptor signaling pathway involved in phagocytosis; thymus development; ERK1 and ERK2 cascade; negative regulation of apolipoprotein binding; транскрипция, ДНК-зависимая; cartilage development; вирусный процесс; response to toxic substance; regulation of stress-activated MAPK cascade; фосфорилирование; outer ear morphogenesis; BMP signaling pathway; response to lipopolysaccharide; развитие щитовидной железы; response to epidermal growth factor; positive regulation of MAP kinase activity; positive regulation of telomerase activity; peptidyl-tyrosine autophosphorylation; ноцицепция; positive regulation of cyclase activity; trachea formation; lipopolysaccharide-mediated signaling pathway; intracellular signal transduction; lung morphogenesis; neural crest cell development; transcription initiation from RNA polymerase I promoter; regulation of early endosome to late endosome transport; positive regulation of telomere maintenance via telomerase; MAPK cascade; positive regulation of histone acetylation; Аксональное наведение; interleukin-1-mediated signaling pathway; fibroblast growth factor receptor signaling pathway; peptidyl-serine phosphorylation; regulation of cellular response to heat; Bergmann glial cell differentiation; regulation of Golgi inheritance; arachidonic acid metabolic process; regulation of cytoskeleton organization; положительная регуляция транскрипции РНК полимеразой II промотор; regulation of phosphatidylinositol 3-kinase signaling; regulation of ossification; positive regulation of gene expression; positive regulation of macrophage chemotaxis; cellular response to amino acid starvation; cellular response to reactive oxygen species; stress-activated MAPK cascade; cellular response to cadmium ion; cellular response to dopamine; positive regulation of metallopeptidase activity; regulation of cellular pH; protein-containing complex assembly; cellular response to tumor necrosis factor; regulation of gene expression; cellular response to organic substance; старение человека; decidualization;
	Sources:Amigo / QuickGO
Ортологи
	5595
	26417
	ENSG00000102882
	ENSMUSG00000063065
	P27361
	Q63844
	NM_001040056; NM_001109891; NM_002746
	NM_011952
	NP_001035145; NP_001103361; NP_002737
	NP_036082
	Викиданные
Править (человек)	Править (мышь)

MAPK3 («митоген-активируемая белковая киназа 3»; англ. mitogen-activated protein kinase 3; p44MAPK; ERK1) — цитозольная серин/треониновая протеинкиназа, семейства MAPK группы ERK^[5], продукт гена MAPK3^[6].

СтруктураПравить

MAPK3 состоит из 379 аминокислот, молекулярная масса 43,1 кДа. Описано 3 изоформы белка, образующиеся в результате альтернативного сплайсинга.

ФункцияПравить

MAPK3, или ERK1, — фермент семейства MAPK из группы киназ, регулируемых внеклеточными сигналами (ERK). Киназа отвечает на разнообразные внешние сигналы и вовлечёна во множество клеточных процессов, таких как пролиферация, клеточная дифференцировка, регуляция клеточного цикла. Активация киназы требует её фосфорилирования другими киназами, расположенными выше в сигнальном каскаде. После активации MAPK3 транслоцируется в клеточное ядро, где фосфорилирует ядерные мишени. Обнаружено несколько изоформы MAPK3, образующиеся в результате альтернативного сплайсинга^[7].

Клиническое значениеПравить

Предполагается, что ген MAPK3 вместе с геном IRAK1 выключается под действием нескольких микроРНК, которые активируются, когда вирус гриппа Alphainfluenzavirus инфицирует лёгкие^[8].

Сигнальные путиПравить

Фармакологическое ингибирование ERK1/2 восстанавливает активность GSK3β и синтез белка в моделе туберозного склероза^[9].

ВзаимодействияПравить

MAPK3 взаимодействует со следующими белками:

DUSP3,^[10]
DUSP6^[11]
GTF2I,^[12]
HDAC4,^[13]
MAP2K1,^[14]^[15]^[16]^[17]^[18]
MAP2K2,^[14]^[15]^[18]
PTPN7,^[19]^[20]^[21]
RPS6KA2^[22]^[23],
SPIB^[24].

ПримечанияПравить

↑ ¹ ² ³ GRCh38: Ensembl release 89: ENSG00000102882 - Ensembl, May 2017
↑ ¹ ² ³ GRCm38: Ensembl release 89: ENSMUSG00000063065 - Ensembl, May 2017
↑ Human PubMed Reference: (неопр.) National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Mouse PubMed Reference: (неопр.) National Center for Biotechnology Information, U.S. National Library of Medicine.
↑ Thomas, Gareth M.; Huganir, Richard L. (1 March 2004). “MAPK cascade signalling and synaptic plasticity”. Nature Reviews Neuroscience. 5 (3): 173—183. DOI:10.1038/nrn1346. ISSN 1471-003X. PMID 14976517. S2CID 205499891.
↑ 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 (неопр.).
↑ 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.
↑ Pal R, Bondar VV, Adamski CJ, Rodney GG, Sardiello M (2017). “Inhibition of ERK1/2 Restores GSK3β Activity and Protein Synthesis Levels in a Model of Tuberous Sclerosis”. Sci. Rep. 7 (1): 4174. DOI:10.1038/s41598-017-04528-5. PMC 5482840. PMID 28646232.
↑ 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.
↑ ¹ ² 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.
↑ ¹ ² 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. S2CID 28868990.
↑ 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.
↑ ¹ ² 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. S2CID 40413956.
↑ 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.

ЛитератураПравить

Peruzzi F, Gordon J, Darbinian N, Amini S (2002). “Tat-induced deregulation of neuronal differentiation and survival by nerve growth factor pathway”. J. Neurovirol. 8 Suppl 2 (2): 91—6. DOI:10.1080/13550280290167885. PMID 12491158.
Meloche S, Pouysségur J (2007). “The ERK1/2 mitogen-activated protein kinase pathway as a master regulator of the G1- to S-phase transition”. Oncogene. 26 (22): 3227—39. DOI:10.1038/sj.onc.1210414. PMID 17496918.
Modulatory Actions of Neuropeptide y on Prostate Cancer Growth: Role of MAP Kinase/ERK 1/2 Activatio, Modulatory actions of neuropeptide Y on prostate cancer growth: role of MAP kinase/ERK 1/2 activation, vol. 604, Advances In Experimental Medicine And Biology, 2007, с. 96–100, ISBN 978-0-387-69114-5, PMID 17695723, doi:10.1007/978-0-387-69116-9_7

СсылкиПравить

[refGRCh38Ensembl-1] ¹ ² ³ GRCh38: Ensembl release 89: ENSG00000102882 - Ensembl, May 2017

[refGRCm38Ensembl-2] ¹ ² ³ GRCm38: Ensembl release 89: ENSMUSG00000063065 - Ensembl, May 2017

[3] Human PubMed Reference: (неопр.) National Center for Biotechnology Information, U.S. National Library of Medicine.

[4] Mouse PubMed Reference: (неопр.) National Center for Biotechnology Information, U.S. National Library of Medicine.

[5] Thomas, Gareth M.; Huganir, Richard L. (1 March 2004). “MAPK cascade signalling and synaptic plasticity”. Nature Reviews Neuroscience. 5 (3): 173—183. DOI:10.1038/nrn1346. ISSN 1471-003X. PMID 14976517. S2CID 205499891.

[pmid9628824-6] 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.

[7] Entrez Gene: MAPK3 mitogen-activated protein kinase 3 (неопр.).

[pmid22822053-8] 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.

[pmid28646232-9] Pal R, Bondar VV, Adamski CJ, Rodney GG, Sardiello M (2017). “Inhibition of ERK1/2 Restores GSK3β Activity and Protein Synthesis Levels in a Model of Tuberous Sclerosis”. Sci. Rep. 7 (1): 4174. DOI:10.1038/s41598-017-04528-5. PMC 5482840. PMID 28646232.

[pmid10224087-10] 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.

[pmid9535927-11] 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.

[pmid10648599-12] 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.

[pmid11114188-13] 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.

[pmid9006895-14] ¹ ² 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.

[pmid8626767-15] ¹ ² 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.

[pmid9733512-16] Elion EA (September 1998). “Routing MAP kinase cascades”. Science. 281 (5383): 1625—6. DOI:10.1126/science.281.5383.1625. PMID 9767029. S2CID 28868990.

[pmid10748187-17] 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.

[pmid8226933-18] ¹ ² 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.

[pmid10702794-19] 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.

[pmid10559944-20] 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. S2CID 40413956.

[pmid10206983-21] 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.

[pmid12832467-22] 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.

[pmid8939914-23] 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.

[pmid8632909-24] 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.

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