Janus kinase 1, Janus kinase 2, Janus kinase 3, Tyrosine kinase 2 (JAK1, JAK2, JAK3, TYK2)

The Janus kinases comprise a family of four intracellular, non-receptor tyrosine kinases (JAK1, JAK2, JAK3, TYK2) that associate with the cytoplasmic domains of diverse cytokine receptors. Upon cytokine binding to their respective receptors, JAKs are activated and mediate phosphorylation of the receptor and downstream STAT proteins, resulting in regulation of gene expression that is essential for immune development, hematopoiesis, host defense, and inflammation. JAK3 expression is mainly restricted to the hematopoietic system, while the other JAKs are more ubiquitous. Dysregulation and mutation of JAKs are implicated in immunodeficiency (e.g., JAK3 mutations cause SCID), myeloproliferative neoplasms (e.g., JAK2 V617F), autoimmune diseases, and cancer. Selective inhibitors of JAKs are approved for treatment of autoimmune diseases and certain malignancies.

Other names

Tyrosine-protein kinase TYK2Tyrosine kinase 2JAK kinasesJAK family

Inhibition of JAK kinase activity, blocking downstream phosphorylation of STAT proteins and subsequent gene transcription in cytokine-activated pathways