Janus kinase 1, Janus kinase 2, Janus kinase 3, and Tyrosine kinase 2 (JAK/TYK)

The Janus kinase (JAK) family, comprising Janus kinase 1 (JAK1), Janus kinase 2 (JAK2), Janus kinase 3 (JAK3), and Tyrosine kinase 2 (TYK2), consists of intracellular non-receptor tyrosine kinases that are essential mediators of the JAK-STAT signaling pathway (Source: UniProt P23458, O60674). These enzymes associate with the cytoplasmic tails of cytokine receptors and, upon ligand binding, phosphorylate both the receptors and downstream Signal Transducer and Activator of Transcription (STAT) proteins to regulate gene expression. This pathway is a central regulator of immune cell development, inflammatory responses, and hematopoiesis. Dysregulation of JAK signaling is implicated in various autoimmune and inflammatory diseases, such as rheumatoid arthritis and atopic dermatitis, as well as hematologic malignancies like myelofibrosis (Source: NIH/NCBI). Therapeutic JAK inhibitors (jakinibs) are used to block these pathways and reduce systemic inflammation. The clinical context of concomitant glucocorticoid therapy refers to the common practice of using JAK inhibitors alongside steroids to manage acute flares or as part of a steroid-sparing strategy. However, this combination requires careful monitoring due to the potential for additive immunosuppression and an increased risk of opportunistic infections (Source: FDA Xeljanz Label).

Other names

Janus kinasesJAKsJAK familyJAK-STAT pathway componentsTyrosine kinase 2

JAK inhibitors competitively bind to the ATP-binding site in the catalytic domain of Janus kinases, preventing their activation and the subsequent phosphorylation of STAT proteins, which blocks the transcription of pro-inflammatory genes (Source: PubMed PMID: 29149516).