TBK1 Antibodies

Serine/threonine-protein kinase TBK1 (TBK1)

Serine/threonine kinase that plays a vital 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 action allows subsequent homodimerization and nuclear translocation of the IRFs leading to transcriptional activation of pro-inflammatory and antiviral genes such as IFNA and IFNB. So as to establish this antiviral state, TBK1 form several diverse complexes whose composition is dependent upon the type of cell and cellular stimuli.

Gene Information

Human
Gene Name:	TBK1
Uniprot:	Q9UHD2
Entrez:	29110

Family

Belongs to:
protein kinase superfamily

Alternative Names

EC 2.7.11; EC 2.7.11.1; FLJ11330; FTDALS4; NAK; NAK serine; NAK serine/threonine-protein kinase TBK 1; NAK; NAKserine/threonine-protein kinase TBK1; NF-kappa-B-activating kinase; NFKB-Activating Kinase; T2K; TANK; TANK binding kinase; TANK-binding kinase 1NF-kB-activating kinase; TBK 1; TBK1

Molecular Weight

Mass (kDA):
83.642 kDA

Genomic Context

Human
Location:	12q14.2
Sequence:	12; NC_000012.12 (64452105..64502114)

Tissue Specificity

Ubiquitous with higher expression in testis. Expressed in the ganglion cells, nerve fiber layer and microvasculature of the retina.

Subcellular Localizations

Cytoplasm. Upon mitogen stimulation or triggering of the immune system, TBK1 is recruited to the exocyst by EXOC2.

Diseases

• Virus Diseases
• Innate Immune Response
• Malignant Neoplasms
• Sting Injury
• Inflammation
• Neoplasms
• Hepatitis
• Infective Disorder
• Hepatitis C
• Bacterial Infections
• Vesicular Stomatitis
• Rna Virus Infections
• Salmonella Infections

• Stomatitis
• Cell Transformation, Neoplastic
• Rheumatoid Arthritis
• Melanoma
• Respirovirus Infections
• Arthritis
• Inflammatory Response

Interacting Proteins

• AGO2
• ATG9A
• AZI2
• CALCOCO2
• CDC42BPG

• Ddx3x
• HSP90AB1
• ICOS
• IKBKE
• IKBKG

• IRF3
• IRF7
• MAVS
• MIB1
• MIB2

• MTPAP
• OPTN
• RIOK3
• STAT6
• TANK

• TBKBP1
• TICAM1
• TMEM173
• TRAF2
• TTC4

• TXLNA
• Txlng

Pathways

• Immune Response
• Innate Immune Response
• Autophagy
• Pathogenesis
• Secretion
• Localization
• Viral Replication
• Response To Virus
• Cytokine Production
• Cell Death
• Rna Interference
• Virulence
• Inflammatory Response

• Response To Lipopolysaccharide
• Type I Interferon Production
• Oncogenesis
• Angiogenesis
• Cell Proliferation
• Cell Cycle
• Parturition

PTMs

• Phosphorylation
• Ubiquitination
• Cleavage
• Sumoylation

• Methylation
• Demethylation
• Isgylation
• Dephosphorylation

Research Areas

• Protein Kinase
• Signal Transduction

For details, visit:
bosterbio.com/bosterbio-gene-info-cards/TBK1

Best Uses of the TBK1 Marker

The TBK1 marker regulates osteoclast development and function. It aids in the transformation of and invasion breast epithelial cell cells. But, how exactly can you make use of this marker? Read on to discover the most crucial uses of this marker. This article was written and edited by Sanbio experts. You can find the most effective TBK1 marker to meet your requirements with their assistance.

The TBK1 regulates the differentiation process and function of osteoclasts

TBK1 is a crucial regulator of bone resorption and the innate immune response and is highly expressed in human OA models that include ACLT mice. In addition, silence of TBK1 blocks cartilage degradation, reduces serum levels of CTX-II, as well as attenuates ECM degradation in cells. Furthermore, TBK1 regulates the activity of the JAK/STAT pathway of signaling, which is involved in OA. However, the exact function of TBK1 in OA is still unclear.

In this study, TBK1 negatively regulates the function and differentiation of osteoclasts. Osteoclasts express TANK protein 12 times more than macrophages derived from bone marrow. The findings of the study suggest that TBK1 negatively regulates the function of NF-kb. Additionally, the knockdown of TBK1 increases the expression of the pro-survival gene TANK.

TBK1 is vital for osteoclast differentiation in osteoarthritis. However, its role in the course of the disease isn't understood fully. This study aims to determine if TBK1 plays a role in the degrading of ECM in OA. To determine this we used C57BL/6J mice with an anterior cruciate ligament transection (ACLT) and ATDC5 cells treated with IL-1b. ECM degradation was assessed using Safranin O-fast green staining and Western Blotting.

Rab13 is a different molecule that plays a major role involved in the osteoclast's function. This protein is crucial for the production of osteoclasts. It is also extensively expressed during the process of differentiation of osteoclasts. Rab13 however, isn't involved in bone resorption or contribute to the process of transcytosis or glucose transport. It is thought to interact with endospanin-2. It is located in small vesicular symbioses located between Golgi networks.

TBK1 has been previously reported to control bone formation in animals. This protein is involved with osteoclastogenesis. Osteoclasts are responsible for breaking down bone and releasing calcium. This gene has been identified as an important regulator of osteoclast differentiation and function in humans. The study also reveals an immediate link between TBK1's role in bone formation and osteoblasts.

Rab27a and -b are multivalent adaptor protein found in the endomembrane cellular system. They interact with Rab7 in the junction of the ruffled membranes in rodent osteoclasts. Both of these proteins may play roles in osteoclast trafficking. However, there are additional ways that TBK1 can affect osteoclast differentiation during bone resorption.

Transfection of cells using siTBK1 inhibits the osteoclasts' differentiation and function by diminuting the expression of ADAMTS-4 MMP13, and SOX9. The siTBK1 transfection increased the expression of collagen II, COL1A2 and ADAMTS-4. Therefore, osteoclast differentiation as well as function are directly affected by the activity of bone-marrow-derived macrophages in the bone marrow.

TBK1 is also involved in innate immunity and autophagy. Autophagy is a homeostatic process within eukaryotic cells that entails the lysosomal degradation of surplus and damaged organelles as well as microorganisms that reside inside the cell. TBK1 regulates autophagy by inhibiting the degradation of macromolecules.

TBK1 expression is high in mice OA models. Moreover, lentivirus-mediated silencing of TBK1 blocks ECM degradation. Silencing TBK1 could be a new option for osteoclast therapy. The effects of silencing TBK1 are not immediately evident in osteoclasts of humans. This finding suggests that TBK1 is a promising drug treatment for osteoporosis.

TBK1 regulates OA and also regulates STAT3 signaling. These results suggest that TBK1 regulation could be a therapeutic target to treat OA. It is important to note that siTBK1 expression on ATDC5 cells does not produce the same beneficial effects as TBK1. The results suggest that TBK1 silencing blocks osteoclast activity in ATDC5 cells.

While osteoclasts are the primary bone resorbing cells in the body, it is vital to control their activity to ensure the development and maintaining an ideal bone structure. Although the RANK-TRAF6-axis is known to trigger osteoclast activation however, a negative mechanism for regulation is yet to be identified. This is the case with the TRAF family member, NF-kB activator or TANK. Both analyses confirmed the presence of this gene that is expressed at higher levels during osteoclastogenesis.

In addition, a cellular receptor called Dickkopf-1 inhibits prostate cancer cells' ability to invade bone. The anti-TBK1 antibody blocks growth and invasion of prostate cancer cells in mice. It also reverses patients with multiple myeloma epigenetic inhibition in osteoblast differentiation. Another study conducted by Giuliani N and Daignault SD has revealed that Dickkopf-1 suppresses osteoclast differentiation through inhibiting the HDAC1's activity.

TBK1 is a key factor in the transformation and invasion of breast epithelial cell lines

The expression of TBK1 is elevated in breast cancer. This gene is involved in the process of tumor cell differentiation. The tumors that express TBK1 have a higher tendency to infiltrate and transform. This gene also plays a part in autophagic maturation. It phosphorylates p62 at S403 and also regulates the vacuole's integrity. Tbk1-expressing tumors display the appearance of a "cobblestone" morphology that is consistent with epithelial cells.

The inhibition of TBK1 increases the metastatic potential of ERa-positive breast cancer cell lines. In contrast, a cell that is deficient in TBK1 is not metastatically spread. MCF-7 cells expressing TBK1 increase lung colonization as well as tumor development. Additionally, TBK1 knockdown cells increase the expression of smad3 as well as p-Smad3, which in turn stimulate tumor growth.

The TBK1 protein promotes the invasion breast epithelial cell cells by controlling cell proliferation and migration. It promotes cell proliferation and migration in a cell-culture model. However, TBK1 is involved in various signaling pathways and its differential relationship with adapter proteins influences its subcellular location. It also shows post-translational modifications such as phosphorylation and acetylation.

In addition to its pro-tumor immune function, TBK1 is also implicated in a variety of other processes that contribute to the growth of tumors. It has been linked to immune evasion and metastatic behavior. In PDA mice, Tbk1 is reduced, which results in an increase in proinflammatory cytokines. This is vital for tumor immune responses.

Additionally, TBK1 is essential in the cGAS-STING-IRF signaling pathway, which is involved in the production of cytokines and interferons of type I. It is also important in the transcription factors that are phosphorylated, such as IRF3. Furthermore, TBK1 kinase activation is dependent on STING activation. It also interacts with the ribosomal membrane protein ERGIC, which is involved in autophagic clearance.

Different types of cancers have been connected to the overexpression TBK1. The protein is usually found in tumors and works as an autophagy regulator that is positive. It regulates the proliferation of cells in breast-cancer cells. Furthermore, TBK1 and IKKe are phosphorylates of RAB7 S72, which regulates the expression of innate immune signaling and the degradation of lysosomal STING.

Researchers used A549 cell line A549 to study the effects of TBK1 in tumor cell transformation and invasion. Cells were seeded in a chamber with six wells and were transfected with siCtrl or TBK1-EF1NEO. After 48 hours of growth, cells were transfected using the TBK1-specific siRNA, or control siRNA. The cells were then exposed to 60Co grays. The cells were stained using E-cadherin antibody.

Metastasis is lessened when functional TBK1 is eliminated. Additionally, TBK1 reduces tumorigenesis and reduces the formation of metastases. Although this gene was once associated with a variety of neurodegenerative diseases but it was not implicated in the development of Parkinson's. There are numerous studies to support these findings, such as the potential role of Tbk1 in the progression of cancer.

Despite the importance of TBK1 in tumorigenesis but its role in regulation of autophagy remains unexplored. It isn't known what the role TBK1 plays in the autophagy process. It is not known what the protein's contribution is to various signaling pathways, and how it regulates the synthesis of autophagic substances. It is implicated in the development of breast cancer and metastases.

TBK1 is involved in the Axl-driven epithelial-mesenchymal transition in KRAS-mutant PDA. The Axl/TBK1 signaling cascade is located above and below KRAS, and the interruption of this signaling pathway may be therapeutic for PDA. However, further research is needed to confirm these findings.

In addition, it appears that TBK1 could also play a role in blocking p -IkBa which is a essential component in the regulation of cell growth. A reduction of TBK1 in cancer cells has not affected the proliferation of KRAS positive cells, suggesting that it could play an important role in the cell proliferation pathway. In addition, its sensitivity different cell differentiation states could influence its ability to support AKT activation.

The IKK family also includes five protein factors that regulate NFkB-mediated inflammation responses and proliferation immune cells. It also regulates the expression of type I IFNs. This is an important function for TBK1 in the development of various types of cancer. It also facilitates the development of resistance to drugs. Therefore, it is important to determine the role played by TBK1 in breast cancer.