It imparts its downstream signaling events by binding to its receptor, FGF inducible 14 protein (Fn14) [14, 15]. 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 [16] (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 [16].

The signaling cascades reported under TWEAK-Fn14 interactions are the canonical and noncanonical NF-κB pathways [15, 17] and the MAPK pathway [17]. There has been a report on crosstalk between Wnt and TWEAK pathways [18]. In myoblasts the PI3K-AKT module has been reported to be inhibited under TWEAK stimulus [19]. AKT phosprorylation leads to the activation of GSK3ß resulting in increase of phospho-GSk3ß and active ß-catenin1 (CTNNB1) (dephosphorylated) levels. GSk3ß and ß-catenin1 remain associated in the cytoplasm, phosphorylation of GSk3ß leads to the dissociation of ß-catenin1 (dephosphorylated) resulting in the nuclear translocation of the protein [20]. Despite of reports on TWEAK binding to other receptors including CD163 [21] and DR3 [22] 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 [23] and can be accessed by any pathway resource to generate a customized pathway.

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