Maintain refrigerated at 2-8°C for up to 6 months. For long term storage store at -20°C in small aliquots to prevent freeze-thaw cycles.

NFkappaB-activating kinase (NAK) also known as TANK binding kinase-1 (TBK1) or tumor necrosis factor receptor−associated factor 2-associated kinase (T2K) is a serine/threonine protein that belongs to the IkB kinase (IKK) family (1). Similar to IKK alpha and beta (2), NAK induces IkB degradation and NF-kB activity. NAK is activated by phorbol ester tumor promoters and growth factors, whereas catalytically inactive NAK specifically inhibits activation of NF-kB by protein kinase C-epsilon (PKCepsilon). NAK specifically phosphorylates IkB alpha on Serine 36 and NFkB subunit RelA (p65) on Serine 536 (3). NAK is also known to interact with TANK, TRAF-2 and TRIF (4).

A synthetic peptide corresponding to residues in the N-term of human NAK was used as immunogen.

Rabbit

50 mM Tris-Glycine (pH 7.4), 0.15 M NaCl, 40% Glycerol, 0.01% sodium azide and 0.05% BSA.

1. Pomerantz, J. L.; Baltimore, D. : EMBO J. 18: 6694-6704, 1999.<br>2. Karin, M. (1999) J. Biol. Chem. 274, 27339<br>3. Tojima, Y., Fujimoto, A., Delhase, M., Chen, Y., Hatakeyama, S., Nakayama, K., Kaneko, Y., Nimura, Y., Motoyama, N., Ikeda, K., Karin, M., and Nakanishi, M. (2000) Nature 404, 778<br>4. Nomura, F., Kawai, T., Nakanishi, K., and Akira, S. (2000) Genes Cells 5, 191-202<br>

Human, Mouse, Rat

Serine/threonine-protein kinase TBK1, NF-kappa-B-activating kinase, T2K, TANK-binding kinase 1, TBK1, NAK

WB~~1:2000 IHC~~1:50

Function Serine/threonine kinase that plays an essential role in regulating inflammatory responses to foreign agents. Following activation of toll-like receptors by viral or bacterial components, associates with TRAF3 and TANK and phosphorylates interferon regulatory factors (IRFs) IRF3 and IRF7 as well as DDX3X. This activity allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes including IFNA and IFNB. In order to establish such an antiviral state, TBK1 form several different complexes whose composition depends on the type of cell and cellular stimuli. Thus, several scaffolding molecules including FADD, TRADD, MAVS, AZI2, TANK or TBKBP1/SINTBAD can be recruited to the TBK1-containing-complexes. Under particular conditions, functions as a NF-kappa-B effector by phosphorylating NF-kappa-B inhibitor alpha/NFKBIA, IKBKB or RELA to translocate NF-Kappa-B to the nucleus. Restricts bacterial proliferation by phosphorylating the autophagy receptor OPTN/Optineurin on 'Ser- 177', thus enhancing LC3 binding affinity and antibacterial autophagy. Phosphorylates and activates AKT1. Seems to play a role in energy balance regulation by sustaining a state of chronic, low-grade inflammation in obesity, wich leads to a negative impact on insulin sensitivity. Attenuates retroviral budding by phosphorylating the endosomal sorting complex required for transport-I (ESCRT-I) subunit VPS37C. Phosphorylates Borna disease virus (BDV) P protein. Cellular_Location Cytoplasm. Note=Upon mitogen stimulation or triggering of the immune system, TBK1 is recruited to the exocyst by EXOC2 Tissue_Location Ubiquitous with higher expression in testis. Expressed in the ganglion cells, nerve fiber layer and microvasculature of the retina.