MAP3K8

Mitogen-activated protein kinase kinase kinase 8
Identifiers
Symbols	MAP3K8 ; COT; EST; ESTF; FLJ10486; TPL2; Tpl-2; c-COT
External IDs	Template:OMIM5 Template:MGI HomoloGene: 3812
Gene ontology Molecular function Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Template:GNF GO Cellular component Template:GNF GO Biological process Template:GNF GO
RNA expression pattern
File:PBB GE MAP3K8 205027 s at tn.png
More reference expression data
Orthologs
Template:GNF Ortholog box
Species	Human	Mouse
Entrez	n/a	n/a
Ensembl	n/a	n/a
UniProt	n/a	n/a
RefSeq (mRNA)	n/a	n/a
RefSeq (protein)	n/a	n/a
Location (UCSC)	n/a	n/a
PubMed search	n/a	n/a

Mitogen-activated protein kinase kinase kinase 8, also known as MAP3K8, is a human gene.

This gene was identified by its oncogenic transforming activity in cells. The encoded protein is a member of the serine/threonine protein kinase family. This kinase can activate both the MAP kinase and JNK kinase pathways. This kinase was shown to activate IkappaB kinases, and thus induce the nuclear production of NF-kappaB. This kinase was also found to promote the production of TNF-alpha and IL-2 during T lymphocyte activation. Studies of a similar gene in rat suggested the direct involvement of this kinase in the proteolysis of NF-kappaB1,p105 (NFKB1). This gene may also utilize a downstream in-frame translation start codon, and thus produce an isoform containing a shorter N-terminus. The shorter isoform has been shown to display weaker transforming activity.

Further reading

• Aoki M, Akiyama T, Miyoshi J, Toyoshima K (1991). "Identification and characterization of protein products of the cot oncogene with serine kinase activity". Oncogene. 6 (9): 1515–9. PMID 1833717.CS1 maint: Multiple names: authors list (link)
• Miyoshi J, Higashi T, Mukai H; et al. (1991). "Structure and transforming potential of the human cot oncogene encoding a putative protein kinase". Mol. Cell. Biol. 11 (8): 4088–96. PMID 2072910.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Aoki M, Hamada F, Sugimoto T; et al. (1993). "The human cot proto-oncogene encodes two protein serine/threonine kinases with different transforming activities by alternative initiation of translation". J. Biol. Chem. 268 (30): 22723–32. PMID 8226782.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Chan AM, Chedid M, McGovern ES; et al. (1993). "Expression cDNA cloning of a serine kinase transforming gene". Oncogene. 8 (5): 1329–33. PMID 8479752.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Salmeron A, Ahmad TB, Carlile GW; et al. (1996). "Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase". EMBO J. 15 (4): 817–26. PMID 8631303.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Ballester A, Tobeña R, Lisbona C; et al. (1997). "Cot kinase regulation of IL-2 production in Jurkat T cells". J. Immunol. 159 (4): 1613–8. PMID 9257820.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Ballester A, Velasco A, Tobeña R, Alemany S (1998). "Cot kinase activates tumor necrosis factor-alpha gene expression in a cyclosporin A-resistant manner". J. Biol. Chem. 273 (23): 14099–106. PMID 9603908.CS1 maint: Multiple names: authors list (link)
• Lin X, Mu Y, Cunningham ET; et al. (1998). "Molecular determinants of NF-kappaB-inducing kinase action". Mol. Cell. Biol. 18 (10): 5899–907. PMID 9742107.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Belich MP, Salmerón A, Johnston LH, Ley SC (1999). "TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105". Nature. 397 (6717): 363–8. doi:10.1038/16946. PMID 9950430.CS1 maint: Multiple names: authors list (link)
• Lin X, Cunningham ET, Mu Y; et al. (1999). "The proto-oncogene Cot kinase participates in CD3/CD28 induction of NF-kappaB acting through the NF-kappaB-inducing kinase and IkappaB kinases". Immunity. 10 (2): 271–80. PMID 10072079.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Chiariello M, Marinissen MJ, Gutkind JS (2000). "Multiple mitogen-activated protein kinase signaling pathways connect the cot oncoprotein to the c-jun promoter and to cellular transformation". Mol. Cell. Biol. 20 (5): 1747–58. PMID 10669751.CS1 maint: Multiple names: authors list (link)
• Sánchez-Góngora E, Lisbona C, de Gregorio R; et al. (2000). "COT kinase proto-oncogene expression in T cells: implication of the JNK/SAPK signal transduction pathway in COT promoter activation". J. Biol. Chem. 275 (40): 31379–86. doi:10.1074/jbc.M000382200. PMID 10896655.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Luftig MA, Cahir-McFarland E, Mosialos G, Kieff E (2001). "Effects of the NIK aly mutation on NF-kappaB activation by the Epstein-Barr virus latent infection membrane protein, lymphotoxin beta receptor, and CD40". J. Biol. Chem. 276 (18): 14602–6. doi:10.1074/jbc.C100103200. PMID 11278268.CS1 maint: Multiple names: authors list (link)
• Eliopoulos AG, Davies C, Blake SS; et al. (2002). "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". J. Virol. 76 (9): 4567–79. PMID 11932422.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Kane LP, Mollenauer MN, Xu Z; et al. (2002). "Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription". Mol. Cell. Biol. 22 (16): 5962–74. PMID 12138205.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Strausberg RL, Feingold EA, Grouse LH; et al. (2003). "Generation and initial analysis of more than 15,000 full-length human and mouse cDNA sequences". Proc. Natl. Acad. Sci. U.S.A. 99 (26): 16899–903. doi:10.1073/pnas.242603899. PMID 12477932.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Waterfield MR, Zhang M, Norman LP, Sun SC (2003). "NF-kappaB1/p105 regulates lipopolysaccharide-stimulated MAP kinase signaling by governing the stability and function of the Tpl2 kinase". Mol. Cell. 11 (3): 685–94. PMID 12667451.CS1 maint: Multiple names: authors list (link)
• Channavajhala PL, Wu L, Cuozzo JW; et al. (2004). "Identification of a novel human kinase supporter of Ras (hKSR-2) that functions as a negative regulator of Cot (Tpl2) signaling". J. Biol. Chem. 278 (47): 47089–97. doi:10.1074/jbc.M306002200. PMID 12975377.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Gándara ML, López P, Hernando R; et al. (2003). "The COOH-terminal domain of wild-type Cot regulates its stability and kinase specific activity". Mol. Cell. Biol. 23 (20): 7377–90. PMID 14517305.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)
• Bouwmeester T, Bauch A, Ruffner H; et al. (2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. 6 (2): 97–105. doi:10.1038/ncb1086. PMID 14743216.CS1 maint: Explicit use of et al. (link) CS1 maint: Multiple names: authors list (link)