MAP3K8

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Mitogen-activated protein kinase kinase kinase 8
Identifiers
Symbols MAP3K8 ; COT; EST; ESTF; MEKK8; TPL2; Tpl-2; c-COT
External IDs OMIM191195 MGI1346878 HomoloGene3812 ChEMBL: 4899 GeneCards: MAP3K8 Gene
EC number 2.7.11.25
RNA expression pattern
PBB GE MAP3K8 205027 s at tn.png
More reference expression data
Orthologs
Species Human Mouse
Entrez 1326 26410
Ensembl ENSG00000107968 ENSMUSG00000024235
UniProt P41279 Q07174
RefSeq (mRNA) NM_001244134 NM_007746
RefSeq (protein) NP_001231063 NP_031772
Location (UCSC) Chr 10:
30.72 – 30.75 Mb
Chr 18:
4.33 – 4.35 Mb
PubMed search [1] [2]

Mitogen-activated protein kinase kinase kinase 8 is an enzyme that in humans is encoded by the MAP3K8 gene.[1][2][3]

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.[3] In mice, this gene is known as Tpl2 and it is a tumor suppressor gene whose absence contributes to the development and progression of cancer.[4]

Interactions[edit]

MAP3K8 has been shown to interact with AKT1,[5] CHUK,[6] NFKB2,[7] NFKB1,[7][8] and C22orf25.[9]

References[edit]

  1. ^ Miyoshi J, Higashi T, Mukai H, Ohuchi T, Kakunaga T (Aug 1991). "Structure and transforming potential of the human cot oncogene encoding a putative protein kinase". Mol Cell Biol 11 (8): 4088–96. PMC 361219. PMID 2072910. 
  2. ^ Chan AM, Chedid M, McGovern ES, Popescu NC, Miki T, Aaronson SA (May 1993). "Expression cDNA cloning of a serine kinase transforming gene". Oncogene 8 (5): 1329–33. PMID 8479752. 
  3. ^ a b "Entrez Gene: MAP3K8 mitogen-activated protein kinase kinase kinase 8". 
  4. ^ DeCicco-Skinner, Kathleen. "Loss of tumor progression locus 2 (tpl2) enhances tumorigenesis and inflammation in two-stage skin carcinogenesis". 
  5. ^ Kane, Lawrence P; Mollenauer Marianne N; Xu Zheng; Turck Christoph W; Weiss Arthur (Aug 2002). "Akt-dependent phosphorylation specifically regulates Cot induction of NF-kappa B-dependent transcription". Mol. Cell. Biol. (United States) 22 (16): 5962–74. doi:10.1128/MCB.22.16.5962-5974.2002. ISSN 0270-7306. PMC 133991. PMID 12138205. 
  6. ^ Lin, X; Cunningham E T; Mu Y; Geleziunas R; Greene W C (Feb 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 (UNITED STATES) 10 (2): 271–80. doi:10.1016/S1074-7613(00)80027-8. ISSN 1074-7613. PMID 10072079. 
  7. ^ a b Bouwmeester, Tewis; Bauch Angela, Ruffner Heinz, Angrand Pierre-Olivier, Bergamini Giovanna, Croughton Karen, Cruciat Cristina, Eberhard Dirk, Gagneur Julien, Ghidelli Sonja, Hopf Carsten, Huhse Bettina, Mangano Raffaella, Michon Anne-Marie, Schirle Markus, Schlegl Judith, Schwab Markus, Stein Martin A, Bauer Andreas, Casari Georg, Drewes Gerard, Gavin Anne-Claude, Jackson David B, Joberty Gerard, Neubauer Gitte, Rick Jens, Kuster Bernhard, Superti-Furga Giulio (Feb 2004). "A physical and functional map of the human TNF-alpha/NF-kappa B signal transduction pathway". Nat. Cell Biol. (England) 6 (2): 97–105. doi:10.1038/ncb1086. ISSN 1465-7392. PMID 14743216. 
  8. ^ Belich, M P; Salmerón A; Johnston L H; Ley S C (Jan 1999). "TPL-2 kinase regulates the proteolysis of the NF-kappaB-inhibitory protein NF-kappaB1 p105". Nature (ENGLAND) 397 (6717): 363–8. doi:10.1038/16946. ISSN 0028-0836. PMID 9950430. 
  9. ^ "Molecular Interaction Database". 

Further reading[edit]