Non-receptor tyrosine-protein kinase 2 (TYK2) (TYK2)

Non-receptor tyrosine-protein kinase 2 (TYK2) is a member of the Janus kinase (JAK) family of cytoplasmic tyrosine kinases that play a critical role in mediating signal transduction from cytokine receptors to the STAT (Signal Transducer and Activator of Transcription) pathway [UniProt: P29597]. TYK2 specifically associates with the cytoplasmic domains of type I and II cytokine receptors, facilitating signaling for cytokines such as interferon-alpha (IFN-α), interleukin-12 (IL-12), and interleukin-23 (IL-23) [PubMed: 32669153]. These pathways are central to the innate and adaptive immune responses, particularly in the differentiation and activation of Th1 and Th17 cells. Dysregulation of TYK2 signaling is strongly implicated in the pathogenesis of various autoimmune and inflammatory disorders, including psoriasis, psoriatic arthritis, and systemic lupus erythematosus [PubMed: 29773722]. Consequently, TYK2 has emerged as a high-value therapeutic target in immunology. The development of selective inhibitors, particularly allosteric inhibitors like deucravacitinib that target the pseudokinase (JH2) domain, allows for potent modulation of these inflammatory pathways while avoiding many of the side effects typically associated with less selective JAK1/2/3 inhibitors [PubMed: 35143767].

Other names

Tyrosine kinase 2Janus kinase family member 4JTK1

Inhibitors target either the orthosteric catalytic (JH1) domain or the allosteric pseudokinase (JH2) domain to prevent the phosphorylation of Signal Transducers and Activators of Transcription (STAT) proteins, thereby blocking downstream signaling from Type I interferons, IL-12, and IL-23 [PubMed: 35143767, PubMed: 32669153].