TLR4

By Victoria Osinski

By Victoria Osinski

By Jamshed Arslan, Pharm. D., PhD.

By Jamshed Arslan, Pharm. D., PhD.

Stimulator of interferon genes (STING), also known as TMEM173, promotes the production of the interferon’s IFN-alpha and IFN-beta.  STING possesses three functional domains: a cytoplasmic C-terminal tail, a central globular domain, and four N-terminal transmembrane motifs that attach it to the ER.  The role of STING in the immune response is specific to its ability to sense nucleic acids, particularly dsDNA.

TRIF, also known as toll like receptor adaptor molecule 1 or TICAM1, is known for its role in invading foreign pathogens as part of our innate immune response. TRIF/TICAM1 is a TIR-domain adaptor protein (toll/interleukin-1 receptor) that interacts with the Toll-like receptors (TLRs) through intracellular signaling and recognition of its TIR site.

Toll like receptors (TLRs) are highly conserved proteins that are first known for their role in pathogen recognition and immune response activation.  In order to elicit the necessary immune response in reaction to a foreign pathogen, TLRs trigger cytokine production depending on the behavior patterns of the pathogen itself.  Specifically, TLR4 acts through bacterial lipopolysaccharide (LPS), which composes the outer wall of Gram-negative bacteria.  Bacterial LPS is also a potent activator of the immune system.

The inhibitor of apoptosis proteins (IAPs) are important regulators of cell death and inflammation. The cellular inhibitor of apoptosis protein 2 (cIAP2) contains three Baculovirus IAP repeat (BIR) domains, a Ubiquitin associated (UBA) domain, and a RING domain with E3 ligase activity. cIAP2 inhibits apoptosis through direct inhibition of the pro-apoptotic caspase-3. cIAP2 also regulates cell survival through its role in the tumor necrosis factor alpha (TNF-alpha) signaling pathway.

Toll-like receptor 4 (TLR4) belongs to the family of Toll-like receptors (TLR), and plays a main role in pathogen recognition and innate immunity system activation. The TLR family members are highly conserved proteins that all contain a high degree of structural and functional homology in organisms from Drosophila all the way up to humans. TLRs regulate the cellular cytokine production required for efficient innate immunity development through their recognition of pathogen-associated molecular patterns (PAMPs) expressed across a wide range of ligands, including infectious agents.

IRAK4, also known as Interleukin-1 receptor-associated kinase 4, is a serine/threonine-protein kinase that plays a critical role in initiating innate and adaptive immune responses against foreign pathogens. It activates NF-kappaB in both Toll-like receptor (TLR) and T-cell receptor (TCR) signaling pathways.