Tyrosine kinase 2

Tyrosine Kinase 2

Tyrosine Kinase 2 (TYK2) is a protein-coding gene that plays a crucial role in the immune system. It is a member of the Janus kinase (JAK) family of enzymes, which are involved in signal transduction pathways. TYK2 is primarily expressed in immune cells, such as T cells, B cells, natural killer cells, and dendritic cells.

Structure and Function

TYK2 is composed of several domains, including a kinase domain, a pseudokinase domain, and an N-terminal FERM domain. The kinase domain is responsible for the phosphorylation of tyrosine residues on target proteins, while the pseudokinase domain lacks catalytic activity but is involved in regulating the kinase activity of TYK2. The FERM domain is responsible for protein-protein interactions and plays a role in the localization of TYK2 within the cell.

TYK2 is a key component of the JAK-STAT signaling pathway, which is essential for the regulation of immune responses. Upon activation by cytokines, such as interferons and interleukins, TYK2 phosphorylates and activates downstream signaling molecules, including STAT proteins. These activated STAT proteins then translocate to the nucleus, where they regulate the expression of target genes involved in immune responses.

Role in Disease

Mutations in the TYK2 gene have been associated with various autoimmune and inflammatory diseases. For example, a specific mutation in TYK2 has been linked to an increased risk of developing autoimmune diseases, such as rheumatoid arthritis, systemic lupus erythematosus, and inflammatory bowel disease. These mutations can lead to dysregulated immune responses and contribute to the development of these diseases.

Furthermore, TYK2 inhibitors have shown promise as potential therapeutic targets for the treatment of certain autoimmune diseases. By blocking the activity of TYK2, these inhibitors can modulate the immune response and potentially alleviate symptoms associated with these diseases.

References

1. Stark GR, Darnell JE Jr. The JAK-STAT pathway at twenty. Immunity. 2012;36(4):503-514. doi:10.1016/j.immuni.2012.03.013

2. Schwartz DM, Kanno Y, Villarino A, Ward M, Gadina M, O'Shea JJ. JAK inhibition as a therapeutic strategy for immune and inflammatory diseases. Nat Rev Drug Discov. 2017;16(12):843-862. doi:10.1038/nrd.2017.201

See Also

• Janus kinase
• Signal transduction
• Cytokines
• Autoimmune diseases
• Inflammatory diseases