Biology:MAP3K8
From HandWiki
Short description: Protein-coding gene in the species Homo sapiens
 Generic protein structure example |
Mitogen-activated protein kinase kinase kinase 8 is an enzyme that in humans is encoded by the MAP3K8 gene.[1][2][3]
Function
The gene was identified by its oncogenic transforming activity in cells. The encoded protein is a member of the serine/threonine-specific protein kinase family. This kinase can activate ERK1, ERK2 and p38 MAP kinases.[4][5] 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 start transcription at 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.[3] In mice, the gene is known as TPL2 and is a tumor-suppressor gene whose absence contributes to the development and progression of cancer.[6] However, it functions in other organs as a oncogene, promoting cancer.[7]
Interactions
MAP3K8 has been shown to interact with AKT1,[8] CHUK,[9] NFKB2,[10] NFKB1,[10][11] C22orf25[12] and TNIP2.[13]
References
- ↑ "Structure and transforming potential of the human cot oncogene encoding a putative protein kinase". Molecular and Cellular Biology 11 (8): 4088–96. Aug 1991. doi:10.1128/mcb.11.8.4088. PMID 2072910.
- ↑ "Expression cDNA cloning of a serine kinase transforming gene". Oncogene 8 (5): 1329–33. May 1993. PMID 8479752.
- ↑ 3.0 3.1 "Entrez Gene: MAP3K8 mitogen-activated protein kinase kinase kinase 8". https://www.ncbi.nlm.nih.gov/sites/entrez?Db=gene&Cmd=ShowDetailView&TermToSearch=1326.
- ↑ "Mitogen-activated protein kinases in innate immunity.". Nature Reviews Immunology 13 (9): 679–92. Sep 2013. doi:10.1038/nri3495. PMID 23954936.
- ↑ "TLR and TNF-R1 activation of the MKK3/MKK6-p38α axis in macrophages is mediated by TPL-2 kinase.". Biochemical Journal 473 (18): 2845–61. Sep 2016. doi:10.1042/BCJ20160502. PMID 27402796.
- ↑ DeCicco-Skinner, Kathleen (2011). "Loss of tumor progression locus 2 (tpl2) enhances tumorigenesis and inflammation in two-stage skin carcinogenesis". Oncogene 30 (4): 389–97. doi:10.1038/onc.2010.447. PMID 20935675.
- ↑ DeCicco-Skinner, Kathleen (2011). "Loss of tumor progression locus 2 (tpl2) enhances tumorigenesis and inflammation in two-stage skin carcinogenesis". Oncogene 30 (4): 389–97. doi:10.1038/onc.2010.447. PMID 20935675.
- ↑ "Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription". Molecular and Cellular Biology 22 (16): 5962–74. Aug 2002. doi:10.1128/MCB.22.16.5962-5974.2002. PMID 12138205.
- ↑ "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. Feb 1999. doi:10.1016/S1074-7613(00)80027-8. PMID 10072079.
- ↑ 10.0 10.1 "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology 6 (2): 97–105. Feb 2004. doi:10.1038/ncb1086. PMID 14743216.
- ↑ "TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105". Nature 397 (6717): 363–8. Jan 1999. doi:10.1038/16946. PMID 9950430. Bibcode: 1999Natur.397..363B.
- ↑ "Molecular Interaction Database". http://mint.bio.uniroma2.it/mint/Welcome.do.
- ↑ "ABIN-2 forms a ternary complex with TPL-2 and NF-kappa B1 p105 and is essential for TPL-2 protein stability". Molecular and Cellular Biology 24 (12): 5235–48. Jun 2004. doi:10.1128/MCB.24.12.5235-5248.2004. PMID 15169888.
Further reading
- "Identification and characterization of protein products of the cot oncogene with serine kinase activity". Oncogene 6 (9): 1515–9. Sep 1991. PMID 1833717.
- "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 268 (30): 22723–32. Oct 1993. doi:10.1016/S0021-9258(18)41587-6. PMID 8226782.
- "Activation of MEK-1 and SEK-1 by Tpl-2 proto-oncoprotein, a novel MAP kinase kinase kinase". The EMBO Journal 15 (4): 817–26. Feb 1996. doi:10.1002/j.1460-2075.1996.tb00417.x. PMID 8631303.
- "Cot kinase regulation of IL-2 production in Jurkat T cells". Journal of Immunology 159 (4): 1613–8. Aug 1997. doi:10.4049/jimmunol.159.4.1613. PMID 9257820.
- "Cot kinase activates tumor necrosis factor-alpha gene expression in a cyclosporin A-resistant manner". The Journal of Biological Chemistry 273 (23): 14099–106. Jun 1998. doi:10.1074/jbc.273.23.14099. PMID 9603908.
- "Molecular determinants of NF-kappaB-inducing kinase action". Molecular and Cellular Biology 18 (10): 5899–907. Oct 1998. doi:10.1128/mcb.18.10.5899. PMID 9742107.
- "TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105". Nature 397 (6717): 363–8. Jan 1999. doi:10.1038/16946. PMID 9950430. Bibcode: 1999Natur.397..363B.
- "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. Feb 1999. doi:10.1016/S1074-7613(00)80027-8. PMID 10072079.
- "Multiple mitogen-activated protein kinase signaling pathways connect the cot oncoprotein to the c-jun promoter and to cellular transformation". Molecular and Cellular Biology 20 (5): 1747–58. Mar 2000. doi:10.1128/MCB.20.5.1747-1758.2000. PMID 10669751.
- "COT kinase proto-oncogene expression in T cells: implication of the JNK/SAPK signal transduction pathway in COT promoter activation". The Journal of Biological Chemistry 275 (40): 31379–86. Oct 2000. doi:10.1074/jbc.M000382200. PMID 10896655.
- "Effects of the NIK aly mutation on NF-kappaB activation by the Epstein-Barr virus latent infection membrane protein, lymphotoxin beta receptor, and CD40". The Journal of Biological Chemistry 276 (18): 14602–6. May 2001. doi:10.1074/jbc.C100103200. PMID 11278268.
- "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". Journal of Virology 76 (9): 4567–79. May 2002. doi:10.1128/JVI.76.9.4567-4579.2002. PMID 11932422.
- "Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription". Molecular and Cellular Biology 22 (16): 5962–74. Aug 2002. doi:10.1128/MCB.22.16.5962-5974.2002. PMID 12138205.
- "NF-kappaB1/p105 regulates lipopolysaccharide-stimulated MAP kinase signaling by governing the stability and function of the Tpl2 kinase". Molecular Cell 11 (3): 685–94. Mar 2003. doi:10.1016/S1097-2765(03)00070-4. PMID 12667451.
- "Identification of a novel human kinase supporter of Ras (hKSR-2) that functions as a negative regulator of Cot (Tpl2) signaling". The Journal of Biological Chemistry 278 (47): 47089–97. Nov 2003. doi:10.1074/jbc.M306002200. PMID 12975377.
- "The COOH-terminal domain of wild-type Cot regulates its stability and kinase specific activity". Molecular and Cellular Biology 23 (20): 7377–90. Oct 2003. doi:10.1128/MCB.23.20.7377-7390.2003. PMID 14517305.
- "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nature Cell Biology 6 (2): 97–105. Feb 2004. doi:10.1038/ncb1086. PMID 14743216.
 |  |
