MAP3K8

MAP3K8
Available Structures
PDB	Search:
PDB ID List
Identifiers
	, COT, EST, ESTF, MEKK8, TPL2, Tpl-2, c-COT, AURA2, mitogen-activated protein kinase kinase kinase 8
External IDs
Associated Hereditary Diseases
Disease name	References
Gene ontology
Functions
Cell component
Biological process
	Sources: Amigo / QuickGO
RNA expression profile
Orthologists
	Wikidata
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MAP3K8 ("mitogen-activated protein kinase kinase 8 kinase"; English mitogen-activated protein kinase kinase kinase 8, TAK1 ) is a cytosolic serine / threonine protein kinase of the MAP3K family, a component of several signaling pathways that regulate inflammation and immunity ^[1] ^[2] ^[3] .

Content

Functions

Belongs to the serine / threonine protein kinase family . It is able to activate both ERK1 / 2 and p38 MAP kinases ^[4] ^[5] . It activates IκB kinase and is thus involved in the production of NF-κB . MAP3K8 also stimulates the production of TNF and interleukin 2 during the activation of T-lymphocytes .

Interactions

MAP3K8 interacts with AKT1 , ^[6] CHUK , ^[7] NFKB2 , ^[8] NFKB1 , ^[8] ^[9] C22orf25 ^[10] and TNIP2 . ^[11] .

Notes

↑ Miyoshi J., Higashi T., Mukai H., Ohuchi T., Kakunaga T. Structure and transforming potential of the human cot oncogene encoding a putative protein kinase (Eng.) // Molecular and Cellular Biology : journal. - 1991 .-- August ( vol. 11 , no. 8 ). - P. 4088-4096 . - DOI : 10.1128 / mcb.11.8.4088 . - PMID 2072910 .
↑ Chan AM, Chedid M., McGovern ES, Popescu NC, Miki T., Aaronson SA Expression cDNA cloning of a serine kinase transforming gene (Eng.) // Oncogene : journal. - 1993 .-- May ( vol. 8 , no. 5 ). - P. 1329-1333 . - PMID 8479752 .
↑ Entrez Gene: MAP3K8 mitogen-activated protein kinase kinase kinase 8 (neopr.) .
↑ Arthur JS, Ley SC Mitogen-activated protein kinases in innate immunity. (English) // Nature Reviews Immunology : journal. - Nature Publishing Group , 2013 .-- September ( vol. 13 , no. 9 ). - P. 679-692 . - DOI : 10.1038 / nri3495 . - PMID 23954936 .
↑ Pattison MJ, Mitchell O., Flynn HR, Chen CS, Yang HT, Ben-Addi H., Boeing S., Snijders AP, Ley SC TLR and TNF-R1 activation of the MKK3 / MKK6-p38α axis in macrophages is mediated by TPL-2 kinase. (Eng.) // Biochemical Journal : journal. - 2016 .-- September ( vol. 473 , no. 18 ). - P. 2845-2861 . - DOI : 10.1042 / BCJ20160502 . - PMID 27402796 .
↑ Kane LP, Mollenauer MN, Xu Z., Turck CW, Weiss A. Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription (Eng.) // Molecular and Cellular Biology : journal. - 2002 .-- August ( vol. 22 , no. 16 ). - P. 5962-5974 . - DOI : 10.1128 / MCB.22.16.5962-5974.2002 . - PMID 12138205 .
↑ Lin X., Cunningham ET, Mu Y., Geleziunas R., Greene WC The proto-oncogene Cot kinase participates in CD3 / CD28 induction of NF-kappaB acting through the NF-kappaB-inducing kinase and IkappaB kinases // Immunity: journal. - Cell Press , 1999 .-- February ( vol. 10 , no. 2 ). - P. 271-280 . - DOI : 10.1016 / S1074-7613 (00) 80027-8 . - PMID 10072079 .
↑ ¹ ² Bouwmeester T., Bauch A., Ruffner H., Angrand PO, Bergamini G., Croughton K., Cruciat C., Eberhard D., Gagneur J., Ghidelli S., Hopf C., Huhse B., Mangano R., Michon AM, Schirle M., Schlegl J., Schwab M., Stein MA, Bauer A., Casari G., Drewes G., Gavin AC, Jackson DB, Joberty G., Neubauer G., Rick J ., Kuster B., Superti-Furga G. A physical and functional map of the human TNF-alpha / NF-kappa B signal transduction pathway (Eng.) // Nature Cell Biology : journal. - 2004 .-- February ( vol. 6 , no. 2 ). - P. 97-105 . - DOI : 10.1038 / ncb1086 . - PMID 14743216 .
↑ Belich MP, Salmerón A., Johnston LH, Ley SC TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105 (Eng.) // Nature: journal. - 1999 .-- January ( vol. 397 , no. 6717 ). - P. 363-368 . - DOI : 10.1038 / 16946 . - PMID 9950430 .
↑ Molecular Interaction Database (unopened) (inaccessible link) . Date of treatment January 22, 2019. Archived on May 6, 2006.
↑ Lang V., Symons A., Watton SJ, Janzen J., Soneji Y., Beinke S., Howell S., Ley SC ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is essential for TPL-2 protein stability (Eng.) // Molecular and Cellular Biology : journal. - 2004 .-- June ( vol. 24 , no. 12 ). - P. 5235-5248 . - DOI : 10.1128 / MCB.24.12.5235-5248.2004 . - PMID 15169888 .

Literature

Aoki M., Akiyama T., Miyoshi J., Toyoshima K. Identification and characterization of protein products of the cot oncogene with serine kinase activity (Eng.) // Oncogene : journal. - 1991 .-- September ( vol. 6 , no. 9 ). - P. 1515-1519 . - PMID 1833717 .
Aoki M., Hamada F., Sugimoto T., Sumida S., Akiyama T., Toyoshima K. The human cot proto-oncogene encodes two protein serine / threonine kinases with different transforming activities by alternative initiation of translation / / The Journal of Biological Chemistry : journal. - 1993 .-- October ( vol. 268 , no. 30 ). - P. 22723-22732 . - PMID 8226782 .
Salmeron A., Ahmad TB, Carlile GW, Pappin D., Narsimhan RP, Ley SC Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase (Eng.) // The EMBO Journal : journal. - 1996 .-- February ( vol. 15 , no. 4 ). - P. 817-826 . - PMID 8631303 .
Ballester A., Tobeña R., Lisbona C., Calvo V., Alemany S. Cot kinase regulation of IL-2 production in Jurkat T cells (English) // Journal of Immunology : journal. - 1997 .-- August ( vol. 159 , no. 4 ). - P. 1613-1618 . - PMID 9257820 .
Ballester A., Velasco A., Tobeña R., Alemany S. Cot kinase activates tumor necrosis factor-alpha gene expression in a cyclosporin A-resistant manner (Eng.) // The Journal of Biological Chemistry : journal. - 1998 .-- June ( vol. 273 , no. 23 ). - P. 14099-14106 . - DOI : 10.1074 / jbc.273.23.14099 . - PMID 9603908 .
Lin X., Mu Y., Cunningham ET, Marcu KB, Geleziunas R., Greene WC Molecular determinants of NF-kappaB-inducing kinase action (Eng.) // Molecular and Cellular Biology : journal. - 1998 .-- October ( vol. 18 , no. 10 ). - P. 5899-5907 . - DOI : 10.1128 / mcb.18.10.5899 . - PMID 9742107 .
Belich MP, Salmerón A., Johnston LH, Ley SC TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105 (Eng.) // Nature: journal. - 1999 .-- January ( vol. 397 , no. 6717 ). - P. 363-368 . - DOI : 10.1038 / 16946 . - PMID 9950430 .
Lin X., Cunningham ET, Mu Y., Geleziunas R., Greene WC The proto-oncogene Cot kinase participates in CD3 / CD28 induction of NF-kappaB acting through the NF-kappaB-inducing kinase and IkappaB kinases (English) / / Immunity: journal. - Cell Press , 1999 .-- February ( vol. 10 , no. 2 ). - P. 271-280 . - DOI : 10.1016 / S1074-7613 (00) 80027-8 . - PMID 10072079 .
Chiariello M., Marinissen MJ, Gutkind JS Multiple mitogen-activated protein kinase signaling pathways connect the cot oncoprotein to the c-jun promoter and to cellular transformation (Eng.) // Molecular and Cellular Biology : journal. - 2000 .-- March ( vol. 20 , no. 5 ). - P. 1747-1758 . - DOI : 10.1128 / MCB.20.5.1747-1758.2000 . - PMID 10669751 .
Sánchez-Góngora E., Lisbona C., de Gregorio R., Ballester A., Calvo V., Pérez-Jurado L., Alemany S. COT kinase proton-oncogene expression in T cells: implication of the JNK / SAPK signal transduction pathway in COT promoter activation (Eng.) // The Journal of Biological Chemistry : journal. - 2000 .-- October ( vol. 275 , no. 40 ). - P. 31379-31386 . - DOI : 10.1074 / jbc.M000382200 . - PMID 10896655 .
Luftig MA, Cahir-McFarland E., Mosialos G., Kieff E. Effects of the NIK aly mutation on NF-kappaB activation by the Epstein-Barr virus latent infection membrane protein, lymphotoxin beta receptor, and CD40 (Eng.) // The Journal of Biological Chemistry : journal. - 2001 .-- May ( vol. 276 , no. 18 ). - P. 14602-14606 . - DOI : 10.1074 / jbc.C100103200 . - PMID 11278268 .
Eliopoulos AG, Davies C., Blake SS, Murray P., Najafipour S., Tsichlis PN, Young LS The oncogenic protein kinase Tpl-2 / Cot contributes to Epstein-Barr virus-encoded latent infection membrane protein 1-induced NF-kappaB signaling downstream of TRAF2 (Eng.) // Journal of Virology : journal. - 2002 .-- May ( vol. 76 , no. 9 ). - P. 4567–4579 . - DOI : 10.1128 / JVI.76.9.4567-4579.2002 . - PMID 11932422 .
Kane LP, Mollenauer MN, Xu Z., Turck CW, Weiss A. Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription (Eng.) // Molecular and Cellular Biology : journal. - 2002 .-- August ( vol. 22 , no. 16 ). - P. 5962-5974 . - DOI : 10.1128 / MCB.22.16.5962-5974.2002 . - PMID 12138205 .
Waterfield MR, Zhang M., Norman LP, Sun SC NF-kappaB1 / p105 regulates lipopolysaccharide-stimulated MAP kinase signaling by governing the stability and function of the Tpl2 kinase (Eng.) // Molecular Cell : journal. - 2003 .-- March ( vol. 11 , no. 3 ). - P. 685–694 . - DOI : 10.1016 / S1097-2765 (03) 00070-4 . - PMID 12667451 .
Channavajhala PL, Wu L., Cuozzo JW, Hall JP, Liu W., Lin LL, Zhang Y. Identification of a novel human kinase supporter of Ras (hKSR-2) that functions as a negative regulator of Cot (Tpl2) signaling ( English) // The Journal of Biological Chemistry : journal. - 2003 .-- November ( vol. 278 , no. 47 ). - P. 47089-47097 . - DOI : 10.1074 / jbc.M306002200 . - PMID 12975377 .
Gándara ML, López P., Hernando R., Castaño JG, Alemany S. The COOH-terminal domain of wild-type Cot regulates its stability and kinase specific activity (Eng.) // Molecular and Cellular Biology : journal. - 2003 .-- October ( vol. 23 , no. 20 ). - P. 7377-7390 . - DOI : 10.1128 / MCB.23.20.7377-7390.2003 . - PMID 14517305 .
Bouwmeester T., Bauch A., Ruffner H., Angrand PO, Bergamini G., Croughton K., Cruciat C., Eberhard D., Gagneur J., Ghidelli S., Hopf C., Huhse B., Mangano R. , Michon AM, Schirle M., Schlegl J., Schwab M., Stein MA, Bauer A., Casari G., Drewes G., Gavin AC, Jackson DB, Joberty G., Neubauer G., Rick J., Kuster B., Superti-Furga G. A physical and functional map of the human TNF-alpha / NF-kappa B signal transduction pathway (Eng.) // Nature Cell Biology : journal. - 2004 .-- February ( vol. 6 , no. 2 ). - P. 97-105 . - DOI : 10.1038 / ncb1086 . - PMID 14743216 .

Links

Mitogen-activated protein kinase cascades and participation of Ste20-like protein kinases in them. E. S. Potekhina, E. S. Nadezhdina. Advances in Biological Chemistry, vol. 42, 2002, p. 235-223556.

[pmid2072910-1] Miyoshi J., Higashi T., Mukai H., Ohuchi T., Kakunaga T. Structure and transforming potential of the human cot oncogene encoding a putative protein kinase (Eng.) // Molecular and Cellular Biology : journal. - 1991 .-- August ( vol. 11 , no. 8 ). - P. 4088-4096 . - DOI : 10.1128 / mcb.11.8.4088 . - PMID 2072910 .

[pmid8479752-2] Chan AM, Chedid M., McGovern ES, Popescu NC, Miki T., Aaronson SA Expression cDNA cloning of a serine kinase transforming gene (Eng.) // Oncogene : journal. - 1993 .-- May ( vol. 8 , no. 5 ). - P. 1329-1333 . - PMID 8479752 .

[entrez-3] Entrez Gene: MAP3K8 mitogen-activated protein kinase kinase kinase 8 (neopr.) .

[pmid23954936-4] Arthur JS, Ley SC Mitogen-activated protein kinases in innate immunity. (English) // Nature Reviews Immunology : journal. - Nature Publishing Group , 2013 .-- September ( vol. 13 , no. 9 ). - P. 679-692 . - DOI : 10.1038 / nri3495 . - PMID 23954936 .

[pmid27402796-5] Pattison MJ, Mitchell O., Flynn HR, Chen CS, Yang HT, Ben-Addi H., Boeing S., Snijders AP, Ley SC TLR and TNF-R1 activation of the MKK3 / MKK6-p38α axis in macrophages is mediated by TPL-2 kinase. (Eng.) // Biochemical Journal : journal. - 2016 .-- September ( vol. 473 , no. 18 ). - P. 2845-2861 . - DOI : 10.1042 / BCJ20160502 . - PMID 27402796 .

[pmid12138205-6] Kane LP, Mollenauer MN, Xu Z., Turck CW, Weiss A. Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription (Eng.) // Molecular and Cellular Biology : journal. - 2002 .-- August ( vol. 22 , no. 16 ). - P. 5962-5974 . - DOI : 10.1128 / MCB.22.16.5962-5974.2002 . - PMID 12138205 .

[pmid10072079-7] Lin X., Cunningham ET, Mu Y., Geleziunas R., Greene WC The proto-oncogene Cot kinase participates in CD3 / CD28 induction of NF-kappaB acting through the NF-kappaB-inducing kinase and IkappaB kinases // Immunity: journal. - Cell Press , 1999 .-- February ( vol. 10 , no. 2 ). - P. 271-280 . - DOI : 10.1016 / S1074-7613 (00) 80027-8 . - PMID 10072079 .

[pmid14743216-8] ¹ ² Bouwmeester T., Bauch A., Ruffner H., Angrand PO, Bergamini G., Croughton K., Cruciat C., Eberhard D., Gagneur J., Ghidelli S., Hopf C., Huhse B., Mangano R., Michon AM, Schirle M., Schlegl J., Schwab M., Stein MA, Bauer A., Casari G., Drewes G., Gavin AC, Jackson DB, Joberty G., Neubauer G., Rick J ., Kuster B., Superti-Furga G. A physical and functional map of the human TNF-alpha / NF-kappa B signal transduction pathway (Eng.) // Nature Cell Biology : journal. - 2004 .-- February ( vol. 6 , no. 2 ). - P. 97-105 . - DOI : 10.1038 / ncb1086 . - PMID 14743216 .

[pmid9950430-9] Belich MP, Salmerón A., Johnston LH, Ley SC TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105 (Eng.) // Nature: journal. - 1999 .-- January ( vol. 397 , no. 6717 ). - P. 363-368 . - DOI : 10.1038 / 16946 . - PMID 9950430 .

[10] Molecular Interaction Database (unopened) (inaccessible link) . Date of treatment January 22, 2019. Archived on May 6, 2006.

[pmid15169888-11] Lang V., Symons A., Watton SJ, Janzen J., Soneji Y., Beinke S., Howell S., Ley SC ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is essential for TPL-2 protein stability (Eng.) // Molecular and Cellular Biology : journal. - 2004 .-- June ( vol. 24 , no. 12 ). - P. 5235-5248 . - DOI : 10.1128 / MCB.24.12.5235-5248.2004 . - PMID 15169888 .