TBK1 (human, recombinant)

TANK-binding kinase 1 (TBK1) is a non-canonical inhibitor of NF-κB kinase (IKK) that has an essential role in regulating inflammatory responses to pathogens.¹ Following activation of toll-like receptors by viral DNA, TBK1 interacts with various partners such as STING, MAVS, and TANK to phosphorylate and activate interferon regulatory factors (IRFs) 3 and 7 as well as DEAD-box helicase 3 X-linked (DDX3X), which leads to transcriptional activation of pro-inflammatory and antiviral genes including interferon (IFN) subtypes α and β.^1,2 TBK1 induces nuclear translocation of NF-κB to initiate a pro-inflammatory response via phosphorylation of NF-κB inhibitor α (NFκBIα), IKKβ, or NF-κB p65 subunit (RelA).³ Cytosolic localization of E. coli, Salmonella, and S. pyogenes increases in TBK1^-/- murine embryonic fibroblasts, macrophages, and epithelial cells, suggesting TBK1 maintains vacuolar integrity, which is critical to bacterial clearance.⁴ TBK1 phosphorylates the autophagy receptor optineurin to enhance binding of ubiquitin-like microtubule-associated protein light chain 3 (LC3) modifiers and induce autophagic clearance of S. enterica.⁵ It also binds to severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) non-structural protein 13 (Nsp13), a helicase-triphosphatase and a component of the viral replicase-transcriptase complex.⁶ Cayman’s TBK1 (human, recombinant) protein can be used for ELISA, Western blot and enzymatic assays.

WARNING This product is not for human or veterinary use.

1. Pomerantz, J.L., and Baltimore, D. NF-kB activation by a signaling complex containing TRAF2, TANK and TBK1, a novel IKK-related kinase. EMBO J. 18(23), 6694-6704 (1999).

2. Tanaka, Y., and Chen, Z.J. STING specifies IRF3 phosphorylation by TBK1 in the cytosolic DNA signaling pathway. Sci. Signal 5(214), ra20 (2012).

3. Tojima, Y., Fujimoto, A., Delhase, M., et al. NAK is an IkB kinase-activating kinase. Nature 404(6779), 778-782 (2000).

4. Radtke, A.L., Delbridge, L.M., Balachandran, S., et al. TBK1 protects vacuolar integrity during intracellular bacterial infection. PLoS Pathog. 3(3), e29 (2007).

5. Wild, P., Farhan, H., McEwan, D.G., et al. Phosphorylation of the autophagy receptor optineurin restricts Salmonella growth. Science 333(6039), 228-233 (2011).

6. Gordon, D.E., Jang, G.M., Bouhaddou, M., et al. A SARS-CoV-2 protein interaction map reveals targets for drug repurposing. Nature 583(7816), 459-468 (2020).