Janus kinase and spleen tyrosine kinase (JAK and SYK)

Janus kinases (JAKs) are intracellular, non-receptor tyrosine kinases comprising four family members (JAK1, JAK2, JAK3, TYK2), each with conserved domains mediating cytokine receptor signal transduction through the JAK-STAT pathway. They are essential in regulating immune cell development, hematopoiesis, and responses to cytokines, and are targeted in inflammatory, autoimmune, and neoplastic diseases. Spleen tyrosine kinase (SYK) is another non-receptor tyrosine kinase, involved primarily in signal transduction downstream of immunoreceptors with ITAM motifs (B cell receptor, Fc receptor), as well as integrin and C-type lectin receptor signaling. SYK modulates innate and adaptive immune responses, cell adhesion, platelet activation, and development of certain autoimmune and allergic diseases, and is implicated in hematological cancers. Drugs have been developed to selectively or jointly inhibit JAK and SYK kinases; however, therapies combining both may carry greater risk for adverse effects due to broad immunosuppression and off-target toxicity.

Other names

JAK familyJanus kinasesSYKspleen tyrosine kinasenon-receptor tyrosine kinases

Inhibition of kinase activity to block cytokine receptor and immunoreceptor signaling. Disruption of immune cell activation and proliferation. Suppression of signaling cascades involved in inflammation, hematopoiesis, and autoimmunity.