TWEAK Signaling Pathway (Bos taurus)

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mRNAProteinTWEAK Signaling PathwayProliferationLigand(Myotubes)Inhibited in skeletal muscle cellsProteosome degradationApoptosisEnzyme complexInhibitionAuto catalysisTransportPositive regulation of gene expressionLeads to through unknown mechanismNegative regulation of gene expressionTranslocation UbiquitinationDeubiquitinationSumoylationInduced catalysisProtein-protein interactionAcetylationDephosphorylationLEGENDPhosphorylationRAF1DeacetylationGolgi apparatusEndosomeNucleusMitochondrionDesumoylationMethylationDemethylationPalmitoylationCytoplasmECPlasma membraneMTEndoplasmic reticulumCYPMGONUExtracellularERENProteolytic cleavageRELBNFKB1CYTRAF1NFKB2IKBKBPIL6MAP3K14TRAF3MAPK3HDAC1PTNFRSF12ARAC1TNFSF12TRAF2BIRC2CASP8FADDMAPK1PNFKBIBRIPK1AKT2PTNFSF12TRAF5AKT1PCHUKPBIKBAPCTNNB1DePCCL5MMP9MAP3K7PMAPK8MAPK9PPRELAPGSK3BPMAPK14TNFSF12PCTNNB1CASP3CCL2CCL5NFKB1RELAPCHUKPDegradationRELBNFKB2CASP8CASP7ProliferationJUNNUCYNUCYNUCYNUCYNUStabilization of MAP3K14Induced activationRAF1Protein-protein dissociation(Renal tubular cells)ProliferationProliferation(Endothelial cells)(Endothelial cells)(Osteoblasts)(Tumor cells)AtrophyReceptorTRIM63TNFBIRC3Lysosomal degradationTRAF2TNFTNFTNFRSF12ACYEC


Description

TNF related weak inducer of apoptosis (TWEAK) is a small pleiotropic cytokine of the TNF super family and its gene is located at chromosome 17p13.1. TWEAK has been reported to be expressed in tissues that include heart, brain, kidney and also in mononuclear blood cells. The multiple biological activities of TWEAK include stimulation of cell growth and angiogenesis, induction of inflammatory cytokines, and stimulation of apoptosis. It has been shown to be involved in the induction of cellular proliferation in liver cells, osteoblasts, astrocytes, synoviocytes, kidney cells and skeletal muscles. Furthermore, TWEAK plays a substantial role in cellular differentiation in osteoclasts. TWEAK induces glioma cell survival via imparting resistance to cytotoxic agents. It imparts its downstream signaling events by binding to its receptor, FGF inducible 14 protein (Fn14). Two modes of TWEAK-Fn14 (ligand-receptor) interactions have been proposed (i) the ligand dependent interaction which involves the higher concentration of homotrimeric TWEAK, that binds to low concentration of Fn14 in a heterohexameric complex (ii) ligand-independent interaction when the ligand concentration is lower than the receptor concentration which induces the ligand independent interaction. The receptors homotrimerize to activate the downstream events. The signaling cascades reported under TWEAK-Fn14 interactions are the canonical and noncanonical NF-κB pathways and the MAPK pathway. There has been a report on crosstalk between Wnt and TWEAK pathways. In myoblasts the PI3K-AKT module has been reported to be inhibited under TWEAK stimulus. AKT phosprorylation leads to the activation of GSK3β resulting in increase of phospho-GSk3β and active β-catenin1 (CTNNB1) (dephosphorylated) levels. GSK3β and β-catenin1 remain associated in the cytoplasm, phosphorylation of GSK3β leads to the dissociation of β-catenin1 (dephosphorylated) resulting in the nuclear translocation of the protein. Despite of reports on TWEAK binding to other receptors including CD163 and DR3 the downstream events following the binding is yet to be established. The data provided by us would foster enormous avenues for further studies on TWEAK associated proteins and the related disorders such as cancer and autoimmune diseases. The data would enable therapeutic studies by selecting the pathological events and the simultaneous production of blocking agents. Despite the minimal amount of data, ours can also be used in the overlay of various high throughput data enabling pathway analysis and can be accessed by any pathway resource to generate a customized pathway.

Please access this pathway at NetSlim database.

If you use this pathway, you must cite following paper:

Bhattacharjee, M., Raju, R., Radhakrishnan, A., Nanjappa, V., Muthusamy, B., Singh, K., Kuppusaami, D., Lingala, B. T., Pan, A., Mathur, P. P., Harsha, H. C., Prasad, T. S. K., Atkins, G. J., Pandey, A. and Chatterjee, A. (2012). A Bioinformatics Resource for TWEAK-Fn14 Signaling Pathway. Journal of Signal Transduction. In press.

Comments

HomologyConvert 
This pathway was inferred from Homo sapiens pathway WP2036(79948) with a 100.0% conversion rate.

Quality Tags

Ontology Terms

 

Bibliography

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History

CompareRevisionActionTimeUserComment
89911view13:25, 6 October 2016EgonwModified description
80856view15:28, 30 June 2015MkutmonNew pathway

External references

DataNodes

View all...
NameTypeDatabase referenceComment
AKT1ProteinENSBTAG00000017636 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
AKT2ProteinENSBTAG00000001400 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:208
ApoptosisPathwayWP254 (WikiPathways)
BIKBAProteinENSBTAG00000016683 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4792
BIRC2ProteinENSBTAG00000035735 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:329
BIRC3ProteinENSBTAG00000024918 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:330
CASP3ProteinENSBTAG00000015874 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:836
CASP7ProteinENSBTAG00000006615 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:840
CASP8ProteinENSBTAG00000015718 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:841
CCL2RnaENSBTAG00000037811 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6347
CCL5RnaENSBTAG00000007191 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6352
CHUKProteinENSBTAG00000007591 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1147
CTNNB1ProteinENSBTAG00000016420 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1499
FADDProteinENSBTAG00000018274 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8772
GSK3BProteinENSBTAG00000048057 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2932
HDAC1ProteinENSBTAG00000012698 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3065
IKBKBProteinENSBTAG00000007599 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3551
IL6RnaENSBTAG00000014921 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3569
JUNProteinENSBTAG00000004037 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3725
MAP3K14ProteinENSBTAG00000007084 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000006062
MAP3K7ProteinENSBTAG00000002625 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6885
MAPK14ProteinENSBTAG00000020783 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1432
MAPK1ProteinENSBTAG00000010312 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
MAPK3ProteinENSBTAG00000016156 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
MAPK8ProteinENSBTAG00000007876 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5599
MAPK9ProteinENSBTAG00000004709 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5601
MMP9RnaENSBTAG00000020676 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4318
NFKB1ProteinENSBTAG00000020270 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4790
NFKB2ProteinENSBTAG00000006017 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4791
NFKBIBProteinENSBTAG00000001778 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4793
Proteosome degradationPathwayWP183 (WikiPathways)
RAC1ProteinENSBTAG00000009233 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5879
RAF1ProteinENSBTAG00000045748 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5894
RELAProteinENSBTAG00000013895 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
RELBProteinENSBTAG00000038428 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5971
RIPK1ProteinENSBTAG00000006378 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8737
TNFProteinENSBTAG00000025471 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7124
TNFRSF12AProteinENSBTAG00000012082 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:51330
TNFSF12ProteinENSBTAG00000031725 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8742
TRAF1ProteinENSBTAG00000003012 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7185
TRAF2ProteinENSBTAG00000010497 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7186
TRAF3ProteinENSBTAG00000013475 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7187
TRAF5ProteinENSBTAG00000012020 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7188
TRIM63ProteinENSBTAG00000005085 (Ensembl) HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:84676

Annotated Interactions

No annotated interactions
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