Janus kinase 1, Janus kinase 3 (JAK1, JAK3)

Janus kinase 1 (JAK1) and Janus kinase 3 (JAK3) are members of the Janus kinase family of intracellular, non-receptor tyrosine kinases critically involved in mediating cytokine signaling through the JAK-STAT pathway[1][3][4]. JAK1 is widely expressed in many tissues, whereas JAK3 expression is largely restricted to hematopoietic and immune cells[4]. Both kinases associate with the intracellular domains of type I and II cytokine receptors and play pivotal roles in the transmission of signals from various cytokines (notably IL-2, IL-4, IL-7, IL-9, IL-15, and IL-21 for JAK3), resulting in the activation of downstream STAT transcription factors and regulation of immune cell function[3][7]. JAK1 and JAK3 are considered high-value therapeutic targets for inflammatory and autoimmune disorders, as well as certain cancers, and are inhibited by several approved and investigational drugs[4][7]. Therapeutic JAK1/3 inhibition impairs pathogenic immune signaling, but also carries risks including immune suppression and increased infection susceptibility. Mutations in JAK1 or JAK3 can lead to primary immunodeficiency or contribute to malignancies by promoting uncontrolled cytokine signaling[3][5].

Other names

JAK1 (also known as Janus kinase 1)JAK3 (also known as Janus kinase 3)

Inhibition of JAK1 and/or JAK3 catalytic kinase activity, preventing phosphorylation and activation of STAT proteins downstream of cytokine receptors, leading to suppressed cytokine signaling and immune modulation