TWEAK signaling pathway (WP3236)

Bos taurus

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 [http://www.netpath.org/netslim/tweak_pathway.html NetSlim] database. If you use this pathway, please cite the 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.

Authors

Martina Summer-Kutmon , Egon Willighagen , and Eric Weitz

Activity

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Organisms

Bos taurus

Communities

Annotations

Pathway Ontology

tumor necrosis factor superfamily mediated signaling pathway

Participants

Label Type Compact URI Comment
RAF1 Protein ensembl:ENSBTAG00000045748 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5894
RELB Protein ensembl:ENSBTAG00000038428 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5971
NFKB1 Protein ensembl:ENSBTAG00000020270 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4790
TRAF1 Protein ensembl:ENSBTAG00000003012 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7185
NFKB2 Protein ensembl:ENSBTAG00000006017 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4791
IKBKB Protein ensembl:ENSBTAG00000007599 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3551
MAP3K14 Protein ensembl:ENSBTAG00000007084 HomologyConvert: Homo sapiens to Bos taurus: Original ID = En:ENSG00000006062
TRAF3 Protein ensembl:ENSBTAG00000013475 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7187
MAPK3 Protein ensembl:ENSBTAG00000016156 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5595
HDAC1 Protein ensembl:ENSBTAG00000012698 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3065
TNFRSF12A Protein ensembl:ENSBTAG00000012082 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:51330
RAC1 Protein ensembl:ENSBTAG00000009233 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5879
TNFSF12 Protein ensembl:ENSBTAG00000031725 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8742
TRAF2 Protein ensembl:ENSBTAG00000010497 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7186
BIRC2 Protein ensembl:ENSBTAG00000035735 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:329
CASP8 Protein ensembl:ENSBTAG00000015718 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:841
FADD Protein ensembl:ENSBTAG00000018274 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8772
MAPK1 Protein ensembl:ENSBTAG00000010312 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5594
NFKBIB Protein ensembl:ENSBTAG00000001778 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4793
RIPK1 Protein ensembl:ENSBTAG00000006378 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:8737
AKT2 Protein ensembl:ENSBTAG00000001400 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:208
TRAF5 Protein ensembl:ENSBTAG00000012020 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7188
AKT1 Protein ensembl:ENSBTAG00000017636 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:207
CHUK Protein ensembl:ENSBTAG00000007591 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1147
BIKBA Protein ensembl:ENSBTAG00000016683 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:4792
CTNNB1 Protein ensembl:ENSBTAG00000016420 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1499
MAP3K7 Protein ensembl:ENSBTAG00000002625 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:6885
MAPK8 Protein ensembl:ENSBTAG00000007876 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5599
MAPK9 Protein ensembl:ENSBTAG00000004709 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5601
RELA Protein ensembl:ENSBTAG00000013895 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:5970
GSK3B Protein ensembl:ENSBTAG00000048057 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:2932
MAPK14 Protein ensembl:ENSBTAG00000020783 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:1432
CASP3 Protein ensembl:ENSBTAG00000015874 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:836
CASP7 Protein ensembl:ENSBTAG00000006615 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:840
JUN Protein ensembl:ENSBTAG00000004037 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:3725
TRIM63 Protein ensembl:ENSBTAG00000005085 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:84676
BIRC3 Protein ensembl:ENSBTAG00000024918 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:330
TNF Protein ensembl:ENSBTAG00000025471 HomologyConvert: Homo sapiens to Bos taurus: Original ID = L:7124

References

  1. NetPath: a public resource of curated signal transduction pathways. Kandasamy K, Mohan SS, Raju R, Keerthikumar S, Kumar GSS, Venugopal AK, et al. Genome Biol. 2010 Jan 12;11(1):R3. PubMed Europe PMC Scholia