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MAP3K7 (mitogen-activated protein kinase kinase kinase 7)

Identity

Other namesTAK1
TGF1a
HGNC (Hugo) MAP3K7
LocusID (NCBI) 6885
Location 6q15
Location_base_pair Starts at 91223292 and ends at 91297020 bp from pter ( according to hg19-Feb_2009)  [Mapping]

DNA/RNA

 
  A: The 17 exons are shown as black vertical bars. The exon numbers are shown on top of each exon. The CpG island is shown as a white box. The positions of exons in the cDNA are 1-282, 283-393, 394-459, 460-505, 506-644, 645-768, 770-898, 899-1029, 1030-1111, 1112-1242, 1243-1372, 1373-1453, 1454-1518, 1519-1624, 1625-1686, 1687-1802, and 1803-2850. The sizes (in base pairs) of intron 1 to 16 are 14956, 3073, 6891, 1407, 3451, 2913, 1278, 1499, 2290, 659, 2625, 8150, 12553, 4358, 695, and 1765, respectively.
B: MAP3K7 transcripts.
Description MAP3K7/TAK1 gene spans 71 kb of DNA and contains 17 exons and 16 introns. Exon 1 contains the 5' UTR of the mRNA and encodes 40 amino acid of N-terminal of the protein. Exons 2 to 8 encode the kinase domain. Exon 17 encodes the carboxyl end of the TAK1 protein and contains the 3'UTR. Exon 12 and exon 16 are alternative exons.
The promoter is located between 799 bp and 1215 bp upsteam of the exon 1. The promoter has the character of housekeeping genes: the absence of TATA box, the presence of CpG island and SP1 binding sites.
Transcription Four alternatively spliced transcripts encoding 4 distinct isoforms because of the presence or absence of alternative exons 12 or/and 16 are detected.
Variant A: It lacks an in-frame coding segment, exon 12.
Variant B: This variant contains both alternative exons 12 and 16 and encodes the longest isoform.
Variant C: Variant C lacks the exon 16 resulting in a frame shift in exon 17. The resulting isoform C has a distinct and shorter C terminus when compared with variants A and B.
Variant D: Variant D lacks both exons 12 and 16.
The regulation of the TAK1 mRNA alternative splicing is tissue specific. The different variants of TAK1 may have specialized functions.
Pseudogene No pseudogene of MAP3K7/TAK1 was reported in human.

Protein

Note MAP3K7/TAK1 isoform B contains 606 amino acids (aa) and has a predicted molecular weight of 67 kDa, isoform D contains 491 aa and has a predicted molecular weight of 53.7 kDa, isoform C contains 518 aa and has a predicted molecular weight of 56.7 kDa, and isoform A contains 579 aa and has a predicted molecular weight of 64 kDa.
Description MAP3K7/TAK1 was first identified by screening a mouse cDNA library for clones that could act as MAPKKKs. The mouse TAK1 cDNA encodes a 579-amino acid protein. The mouse TAK1 protein contains a 300-residue COOH-terminal domain and a putative NH2-terminal protein kinase catalytic domain.
The kinase domain has approximately 30% identity to the catalytic domains of Raf-1 and MEKK1. Kondo et al. (1998) cloned human TAK1 from lung cDNA library by screening with mouse TAK1 sequence. Human TAK1 gene encodes a 579-amino-acid protein. The hTAK1 gene has 91.8% identity with the mTAK1 gene at the nucleotide level and has 99.3% to that at the amino acid level. Human TAK1 mRNA with a size of 3.0 kb was observed to express in all the tissues examined by Northern blotting. Kondo et al. (1998) found 2 isoforms of TAK1. Isoform 2 had an insertion of 27 amino acids between amino acids 403 and 404 of isoform 1 which corresponded to the mTAK1 sequence previously identified by Yamaguchi et al. (1995). The two isoforms were expressed at different ratios. Isoform 1 (Variant A) was predominantly expressed in brain, heart and spleen while the isoform 2 (Variant B) was preferentially in the kidney.
Independently, Sakurai et al. (1998) cloned hTAK1 as well as two alternatively spliced isoforms. Human TAK1a (Variant A) has 99.3% identity to murine TAK1. TAK1b (Variant B) had an insertion of 27 amino acids and TAK1c had a deletion of 39 amino acids in the carboxyl-terminal region. The catalytic domains of these three isoforms were 100% identical to that of murine TAK1. The mRNA for TAK1a and TAK1b were expressed in Hela, Jurkat and THP1 cells and TAK1a mRNA expessed predominantly in these cell lines. TAK1c mRNA (Variant C) was expressed only in Hela cells. Northern blot analysis revealed the expression of TAK1 mRNA in all the human tissues examined with the size of 3.2 and 5.7 kb. Dempsey et al. (2000) identified a fourth splice variant of TAK1 called TAK1d (Variant D). TAK1d lacked the two alternative exons and encoded a 491 amino acid protein. TAK1a and b were the most abundant forms in most tissues examined. The carboxyl-end variant TAK1 proteins were unlikely to interfere with the catalytic activity of TAK1 or its interaction with TAB1 since both of which involve the N terminus, but may affect its interaction with TAB2 which associates with the carboxyl-ends of the TAK1 proteins.
Expression TAK1 was ubiquitously expressed in all tissues. TAK1a (variant A) was the most abundant form in heart, liver, skeletal muscle, ovary, spleen and peripheral blood mononuclear cells; TAK1b (Variant B) was more abundant in brain, kidney, prostate and small intestine; TAK1c (Variant C) is ubiquitously expressed and predominantly in prostate; and TAK1d (Variant D) existed in most tested tissues as a minor variant.
Localisation TAK1 is mostly localized in cytoplasm.
Function TAK1 is a member of the serine/threonine protein kinase family. It can be activated by transforming growth factor-beta (TGF-b) and TAK1 deletion mutant missing the N-terminal 22 amino acid is constitutively active. In response to TGF-b, TAK1 can phosphorylate and activate MAP kinase kinases MKK3, MKK4 and MKK6. TAK1 can activate NF-kB in the presence of TAB1. TAK1 is also involved in pro-inflammatory cytokines signaling by activating two kinase pathways. One is a MAPK cascade that leads to the activation of JNK and the other is IkB kinase cascade that causes the activation of NF-kB. It was shown that TRAF6 is a signal mediator that activates IKK and JNK in response to pro-inflammatory cytokine interleukin 1. The activation of IKK by TRAF6 requires two intermediary factors, TRAF6-regulated IKK activator 1 (TRIKA1) and TRIKA2. TRIKA1 is an ubiquitin-conjugating enzyme complex consisted of Ubc13 and Uev1A. TRIKA1, together with TRAF6, catalyze the formation of a Lys63-linked polyubiquitin chain that mediates IKK activation. TRIKA2 is composed of TAK1, TAB1 and TAB2.
The activation of TAK1 kinase complex is dependent on its polyubiquitination by the TRAF6-Ubc complex and phosphorylation of several residues within the kinase activation loop by yet-to-be identified kinases. The ubiquitinated TAK1 can phosphorylate IKKbeta specifically at S177 and S181. Mutation analysis revealed that a point mutation in the ATP-binding domain of TAK1 (K63W), which abolished its kinase activity, was unable to activate IKK. TAK1 was activated by auto-phosphorylation on Ser192 and dual phosphorylation of Thr-178 and Thr-184 residues within the activation loop. Mutation of a conserved serine residue (Ser192) in the activation loop between kinase domain VII and VIII abrogated the phosphorylation and activation of TAK1. TAK1 is linked to TRAFs by two adaptor proteins TAB2 and TAB3. The interaction of TAB2/TAB3 with TAK1 is essential for the activation of signaling pathway mediated by IL-1.
It was shown that protein phosphatase 2Cepsilon (PP2Cepsilon) inhibited the IL-1 and TAK1 induced activation of MKK4-JNK or MKK3-p38 signaling pathway. PP2Cepsilon inactivated TAK1 by associating with and dephosphorylating TAK1. A type-2A phosphatase, protein phosphatase 6 (PP6), was also identified as a TAK1-binding protein. PP6 repressed TAK1 activity by dephosphorylating Thr187.
Homology Human TAK1-like (TAKL) gene encoded a 242 amino acid protein which shared a homology with human TAK1. The amino acid sequences of TAK1 were highly conserved between human and mouse.

Mutations

Note No mutation of human MAP3K7 was reported.

Implicated in

Entity Breast cancer
Note TGF-b1 signaling is involved in tumor angiogenesis and metastasis by regulating matrix proteosis. MMP-9 is an important component of these TGF-b1 responses. TAK1 is important for TGF-b1 regulation of MMP9 and metastatic potential of breast cancer cell line MDA-MB231. Suppression of TAK1 reduces the expression of MMP9 and tumor cell invasion.
TAK1 and NFkB are required for the human MCF10A-CA1a breast cancer cells to undergo invasion in response to TGF-b. A novel TAB1:TAK1: IKKb: NFkB signaling axis forms aberrantly in breast cancer cells and enables oncogenic signaling by TGF-b.
  
Entity Lung cancer
Note Mutation analysis: Study on 39 lung cancer specimens and 16 lung cancer cell lines indicated that hTAK1 was not a frequent target for genetic alternations in lung cancer.

TAK1 variant D activated by siRNAs of specific sequences leads to down stream activation of p38 MAPK and JNK but not NFkB pathway. In human lung cancer cell line NCI-H460 the activation of these pathway cause cell cycle arrest and apoptosis. It suggests that TAK1 D may be a new and promising therapeutic target for the treatment of non-small cell lung cancer.
Telomeres are essential elements at the ends of chromosomes that contribute to chromosomal stability. The length of the telomere is maintained by the telomerase holoenzyme, which contains the reverse transcriptase hTERT as a major enzymatic subunit. The activity of telomerase is absent in most normal human cells because of the downregulation of the hTERT transcript resulting in the shortening of telomeres after each replicative cycle. However, in immortalized cells and cancer cells, the telomere lengths are maintained through an increase in hTERT expression. TAK1 can repress the transcription of hTERT in A549 human lung adenocarcinoma cell line and this repression is caused by recruitment of HDAC to the hTERT promoter.

  
Entity Cervical carcinoma
Note Tumor necrosis factor (TNF)-related apoptosis-inducing ligand (TRAIL), a member of TNFa ligand family, induces apoptosis in a variety of tumor cells. TRAIL induced the delayed phosphorylation of TAK1 in human cervical carcinoma HeLa cells. TRAIL induced apoptosis was enhanced by downregulation of TAK1.
  
Entity Head and neck squamous cell carcinoma
Note NFkB was constitutively activated in head and neck squamous cell carcinoma (HNSCC). Constitutive activation of NFkB in HNSCC was caused by constitutive activation of IKK. Constitutive activation of NFkB is mediated through the TRADD-TRAF2-RIP-TAK1-IKK pathway.
  
Entity Arthritis
Note Exercise/joint mobility has therapeutic potency for inflammatory joint diseases such as rheumatoid and osteoarthritis. The biomechanical signals at physiological magnitudes are potent inhibitors of inflammation induced by NFkB activation in fibrochondrocytes. The biomechanical signals exert anti-inflammatory effects by inhibiting phosphorylation of TAK1.
JNK is essential for metalloproteinase (MMP) gene expression and joint destruction in inflammatory arthritis. TAK1 is an upstream kinase of JNK. TAK1 play an important role for the IL1b induced JNK activation and the JNK induced gene expression in fibroblast-like synoviocytes (FLSs). It suggests that TAK1 is a potential therapeutic target to modulate synoviocyte activation in rheumatoid arthritis (RA).
  
Entity Inflammation
Note Pro-inflammatory molecules lipopolysaccharide and Interleukin 1 trigger the activation of TAK1, which in turn activates multiple kinase JNK, p38, IKK and PKB/Akt which are important components of kinase cascades involved in inflammation. Thus TAK1 plays an important role in inflammation.
  
Entity Human airway epithelial cells
Note Act1/TRAF6/TAK1-mediated NF-kB activation stimulated by IL-17A regulates gene induction in human airway epithelial cells. Dominant negative TAK1 reduces IL-17A induced gene expression.
  

External links

Nomenclature
HGNC (Hugo)MAP3K7   6859
Cards
AtlasMAP3K7ID454ch6q15
Entrez_Gene (NCBI)MAP3K7  6885  mitogen-activated protein kinase kinase kinase 7
GeneCards (Weizmann)MAP3K7
Ensembl (Hinxton)ENSG00000135341 [Gene_View]  chr6:91223292-91297020 [Contig_View]  MAP3K7 [Vega]
ICGC DataPortalENSG00000135341
cBioPortalMAP3K7
AceView (NCBI)MAP3K7
Genatlas (Paris)MAP3K7
WikiGenes6885
SOURCE (Princeton)NM_003188 NM_145331 NM_145332 NM_145333
Genomic and cartography
GoldenPath (UCSC)MAP3K7  -  6q15   chr6:91223292-91297020 -  6q15   [Description]    (hg19-Feb_2009)
EnsemblMAP3K7 - 6q15 [CytoView]
Mapping of homologs : NCBIMAP3K7 [Mapview]
OMIM602614   
Gene and transcription
Genbank (Entrez)AB009356 AB009357 AB009358 AF218074 AI147171
RefSeq transcript (Entrez)NM_003188 NM_145331 NM_145332 NM_145333
RefSeq genomic (Entrez)AC_000138 NC_000006 NC_018917 NG_011966 NT_025741 NW_001838987 NW_004929327
Consensus coding sequences : CCDS (NCBI)MAP3K7
Cluster EST : UnigeneHs.594838 [ NCBI ]
CGAP (NCI)Hs.594838
Alternative Splicing : Fast-db (Paris)GSHG0026783
Alternative Splicing GalleryENSG00000135341
Gene ExpressionMAP3K7 [ NCBI-GEO ]     MAP3K7 [ SEEK ]   MAP3K7 [ MEM ]
Protein : pattern, domain, 3D structure
UniProt/SwissProtO43318 (Uniprot)
NextProtO43318  [Medical]
With graphics : InterProO43318
Splice isoforms : SwissVarO43318 (Swissvar)
Catalytic activity : Enzyme2.7.11.25 [ Enzyme-Expasy ]   2.7.11.252.7.11.25 [ IntEnz-EBI ]   2.7.11.25 [ BRENDA ]   2.7.11.25 [ KEGG ]   
Domaine pattern : Prosite (Expaxy)PROTEIN_KINASE_ATP (PS00107)    PROTEIN_KINASE_DOM (PS50011)    PROTEIN_KINASE_ST (PS00108)   
Domains : Interpro (EBI)Kinase-like_dom [organisation]   MAPKKK7 [organisation]   Prot_kinase_dom [organisation]   Protein_kinase_ATP_BS [organisation]   Ser-Thr/Tyr_kinase_cat_dom [organisation]   Ser/Thr_kinase_AS [organisation]  
Related proteins : CluSTrO43318
Domain families : Pfam (Sanger)Pkinase_Tyr (PF07714)   
Domain families : Pfam (NCBI)pfam07714   
DMDM Disease mutations6885
Blocks (Seattle)O43318
PDB (SRS)2EVA    2YIY    4GS6    4L3P    4L52    4L53   
PDB (PDBSum)2EVA    2YIY    4GS6    4L3P    4L52    4L53   
PDB (IMB)2EVA    2YIY    4GS6    4L3P    4L52    4L53   
PDB (RSDB)2EVA    2YIY    4GS6    4L3P    4L52    4L53   
Human Protein AtlasENSG00000135341 [gene] [tissue] [antibody] [cell] [cancer]
Peptide AtlasO43318
HPRD04011
IPIIPI00295738   IPI00218566   IPI00218567   IPI00909160   IPI00241935   IPI00641808   
Protein Interaction databases
DIP (DOE-UCLA)O43318
IntAct (EBI)O43318
FunCoupENSG00000135341
BioGRIDMAP3K7
InParanoidO43318
Interologous Interaction database O43318
IntegromeDBMAP3K7
STRING (EMBL)MAP3K7
Ontologies - Pathways
Ontology : AmiGOactivation of MAPKK activity  activation of MAPK activity  activation of MAPK activity  magnesium ion binding  angiogenesis  neural tube formation  toll-like receptor signaling pathway  positive regulation of T cell cytokine production  MyD88-dependent toll-like receptor signaling pathway  MyD88-independent toll-like receptor signaling pathway  protein kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  MAP kinase kinase activity  MAP kinase kinase kinase activity  protein binding  ATP binding  nucleus  Ada2/Gcn5/Ada3 transcription activator complex  cytoplasm  cytosol  plasma membrane  transcription, DNA-templated  apoptotic process  transforming growth factor beta receptor signaling pathway  I-kappaB kinase/NF-kappaB signaling  activation of NF-kappaB-inducing kinase activity  I-kappaB phosphorylation  JNK cascade  JNK cascade  IkappaB kinase complex  endosome membrane  positive regulation of interleukin-2 production  toll-like receptor 2 signaling pathway  toll-like receptor 3 signaling pathway  toll-like receptor 4 signaling pathway  toll-like receptor 5 signaling pathway  toll-like receptor 9 signaling pathway  toll-like receptor 10 signaling pathway  TRIF-dependent toll-like receptor signaling pathway  nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway  Fc-epsilon receptor signaling pathway  toll-like receptor TLR1:TLR2 signaling pathway  toll-like receptor TLR6:TLR2 signaling pathway  positive regulation of I-kappaB kinase/NF-kappaB signaling  positive regulation of JUN kinase activity  positive regulation of JUN kinase activity  histone H3 acetylation  innate immune response  positive regulation of JNK cascade  T cell receptor signaling pathway  T cell receptor signaling pathway  positive regulation of T cell activation  positive regulation of NF-kappaB transcription factor activity  stress-activated MAPK cascade  stress-activated MAPK cascade  nucleotide-binding oligomerization domain containing signaling pathway  scaffold protein binding  negative regulation of apoptotic signaling pathway  
Ontology : EGO-EBIactivation of MAPKK activity  activation of MAPK activity  activation of MAPK activity  magnesium ion binding  angiogenesis  neural tube formation  toll-like receptor signaling pathway  positive regulation of T cell cytokine production  MyD88-dependent toll-like receptor signaling pathway  MyD88-independent toll-like receptor signaling pathway  protein kinase activity  protein serine/threonine kinase activity  protein serine/threonine kinase activity  MAP kinase kinase activity  MAP kinase kinase kinase activity  protein binding  ATP binding  nucleus  Ada2/Gcn5/Ada3 transcription activator complex  cytoplasm  cytosol  plasma membrane  transcription, DNA-templated  apoptotic process  transforming growth factor beta receptor signaling pathway  I-kappaB kinase/NF-kappaB signaling  activation of NF-kappaB-inducing kinase activity  I-kappaB phosphorylation  JNK cascade  JNK cascade  IkappaB kinase complex  endosome membrane  positive regulation of interleukin-2 production  toll-like receptor 2 signaling pathway  toll-like receptor 3 signaling pathway  toll-like receptor 4 signaling pathway  toll-like receptor 5 signaling pathway  toll-like receptor 9 signaling pathway  toll-like receptor 10 signaling pathway  TRIF-dependent toll-like receptor signaling pathway  nucleotide-binding domain, leucine rich repeat containing receptor signaling pathway  Fc-epsilon receptor signaling pathway  toll-like receptor TLR1:TLR2 signaling pathway  toll-like receptor TLR6:TLR2 signaling pathway  positive regulation of I-kappaB kinase/NF-kappaB signaling  positive regulation of JUN kinase activity  positive regulation of JUN kinase activity  histone H3 acetylation  innate immune response  positive regulation of JNK cascade  T cell receptor signaling pathway  T cell receptor signaling pathway  positive regulation of T cell activation  positive regulation of NF-kappaB transcription factor activity  stress-activated MAPK cascade  stress-activated MAPK cascade  nucleotide-binding oligomerization domain containing signaling pathway  scaffold protein binding  negative regulation of apoptotic signaling pathway  
Pathways : BIOCARTATGF beta signaling pathway [Genes]    ALK in cardiac myocytes [Genes]    FAS signaling pathway ( CD95 ) [Genes]    NF-kB Signaling Pathway [Genes]    TNFR1 Signaling Pathway [Genes]    WNT Signaling Pathway [Genes]    Signal transduction through IL1R [Genes]    NFkB activation by Nontypeable Hemophilus influenzae [Genes]    Thrombin signaling and protease-activated receptors [Genes]    MAPKinase Signaling Pathway [Genes]    p38 MAPK Signaling Pathway [Genes]    Toll-Like Receptor Pathway [Genes]   
Pathways : KEGGMAPK signaling pathway    NF-kappa B signaling pathway    Wnt signaling pathway    Osteoclast differentiation    Adherens junction    Toll-like receptor signaling pathway    NOD-like receptor signaling pathway    RIG-I-like receptor signaling pathway    T cell receptor signaling pathway    TNF signaling pathway    Leishmaniasis    Toxoplasmosis    Measles    Herpes simplex infection    Epstein-Barr virus infection   
Protein Interaction DatabaseMAP3K7
Wikipedia pathwaysMAP3K7
Gene fusion - rearrangments
Polymorphisms : SNP, mutations, diseases
SNP Single Nucleotide Polymorphism (NCBI)MAP3K7
snp3D : Map Gene to Disease6885
SNP (GeneSNP Utah)MAP3K7
SNP : HGBaseMAP3K7
Genetic variants : HAPMAPMAP3K7
Exome VariantMAP3K7
1000_GenomesMAP3K7 
ICGC programENSG00000135341 
Somatic Mutations in Cancer : COSMICMAP3K7 
CONAN: Copy Number AnalysisMAP3K7 
Mutations and Diseases : HGMDMAP3K7
Mutations and Diseases : intOGenMAP3K7
Genomic VariantsMAP3K7  MAP3K7 [DGVbeta]
dbVarMAP3K7
ClinVarMAP3K7
Pred. of missensesPolyPhen-2  SIFT(SG)  SIFT(JCVI)  Align-GVGD  MutAssessor  Mutanalyser  
Pred. splicesGeneSplicer  Human Splicing Finder  MaxEntScan  
Diseases
OMIM602614   
MedgenMAP3K7
GENETestsMAP3K7
Disease Genetic AssociationMAP3K7
Huge Navigator MAP3K7 [HugePedia]  MAP3K7 [HugeCancerGEM]
General knowledge
Homologs : HomoloGeneMAP3K7
Homology/Alignments : Family Browser (UCSC)MAP3K7
Phylogenetic Trees/Animal Genes : TreeFamMAP3K7
Chemical/Protein Interactions : CTD6885
Chemical/Pharm GKB GenePA30603
Clinical trialMAP3K7
Cancer Resource (Charite)ENSG00000135341
Other databases
Probes
Litterature
PubMed259 Pubmed reference(s) in Entrez
CoreMineMAP3K7
iHOPMAP3K7
OncoSearchMAP3K7

Bibliography

TAK1: molecular cloning and characterization of a new member of the nuclear receptor superfamily.
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PMID 7708055
 
Identification of a member of the MAPKKK family as a potential mediator of TGF-beta signal transduction.
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TAK1 regulates multiple protein kinase cascades activated by bacterial lipopolysaccharide.
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TAK1 is a ubiquitin-dependent kinase of MKK and IKK.
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PMID 11460167
 
Regulation of the interleukin-1-induced signaling pathways by a novel member of the protein phosphatase 2C family (PP2Cepsilon).
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TAK1 is critical for IkappaB kinase-mediated activation of the NF-kappaB pathway.
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Cloning and characterization of a novel human TGF-beta activated kinase-like gene.
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TAK1-binding protein 2 facilitates ubiquitination of TRAF6 and assembly of TRAF6 with IKK in the IL-1 signaling pathway.
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Blockade of transforming growth factor-beta-activated kinase 1 activity enhances TRAIL-induced apoptosis through activation of a caspase cascade.
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Protein phosphatase 6 down-regulates TAK1 kinase activation in the IL-1 signaling pathway.
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J Biol Chem. 2006 Dec 29;281(52):39891-6. Epub 2006 Nov 1.
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TAK1-dependent signaling requires functional interaction with TAB2/TAB3.
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Regulation of the JNK pathway by TGF-beta activated kinase 1 in rheumatoid arthritis synoviocytes.
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PMID 17559674
 
Evidence that TNF-TNFR1-TRADD-TRAF2-RIP-TAK1-IKK pathway mediates constitutive NF-kappaB activation and proliferation in human head and neck squamous cell carcinoma.
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PMID 16953224
 
Biomechanical signals suppress TAK1 activation to inhibit NF-kappaB transcriptional activation in fibrochondrocytes.
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J Immunol. 2007 Nov 1;179(9):6246-54.
PMID 17947700
 
Molecular Mechanism of TAK1-Induced Repression of hTERT Transcription.
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TAK1 mRNA expression in the tumor tissue of locally advanced head and neck Cancer Patients.
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TAK1 is required for TGF-beta 1-mediated regulation of matrix metalloproteinase-9 and metastasis.
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Phosphorylation of Thr-178 and Thr-184 in the TAK1 T-loop is required for interleukin (IL)-1-mediated optimal NFkappaB and AP-1 activation as well as IL-6 gene expression.
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Contributor(s)

Written03-2009Hui Hui Tang, Kam C Yeung
Department of Cancer Biology and Biochemistry, College of Medicine, Univeristy of Toledo, Health Science Campus, 3035 Arlington Ave., Toledo, OH 43614, USA

Citation

This paper should be referenced as such :
Tang, HH ; Yeung, KC
MAP3K7 (mitogen-activated protein kinase kinase kinase 7)
Atlas Genet Cytogenet Oncol Haematol. 2010;14(3):-.
Free online version   Free pdf version   [Bibliographic record ]
URL : http://AtlasGeneticsOncology.org/Genes/MAP3K7ID454ch6q15.html

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