Janus kinase (JAK) (JAK)

Janus kinases (JAKs) are a family of intracellular, non-receptor tyrosine kinases that mediate signal transduction from cytokine receptors through the JAK-STAT pathway (StatPearls, 2023). The family comprises four members: JAK1, JAK2, JAK3, and TYK2, which associate with the cytoplasmic tails of various cytokine receptors (UniProt, 2024). When a cytokine binds its receptor, JAKs are activated and phosphorylate the receptor, creating docking sites for Signal Transducers and Activators of Transcription (STAT) proteins (PubMed, 2021). These STAT proteins are then phosphorylated, dimerize, and translocate to the nucleus to modulate the transcription of genes essential for immune cell activation, proliferation, and survival (NIH, 2023). Tofacitinib is a potent, oral small-molecule inhibitor that preferentially targets JAK1 and JAK3, with moderate activity against JAK2 (PubChem, 2024). By inhibiting these enzymes, tofacitinib disrupts the signaling of multiple interleukins (e.g., IL-2, IL-6, IL-15, and IL-21) and interferons, which are pivotal in the pathogenesis of autoimmune diseases (FDA, 2021). Consequently, it is used to treat conditions like rheumatoid arthritis, psoriatic arthritis, and ulcerative colitis by reducing systemic inflammation and the overactive immune response (Mayo Clinic, 2023).

Other names

JAKsJanus kinase familyNon-receptor tyrosine kinase JAKJAK1/2/3

ATP-competitive inhibition of Janus kinases, preventing STAT phosphorylation and downstream gene transcription.