JAK-STAT signaling pathway (JAK-STAT)

The JAK-STAT pathway is a highly conserved signaling cascade that links cell surface receptor engagement, especially by cytokines and growth factors, to gene transcription in the nucleus. The pathway is initiated when extracellular signaling molecules bind to cell surface receptors, activating receptor-associated tyrosine kinases of the Janus kinase (JAK) family (JAK1, JAK2, JAK3, TYK2), which then phosphorylate both the receptors and signal transducer and activator of transcription (STAT) proteins (STAT1, STAT2, STAT3, STAT4, STAT5A, STAT5B, STAT6). Activated STATs dimerize and translocate to the nucleus to drive the transcription of genes critical for immunity, proliferation, differentiation, and survival. Dysregulation of the JAK-STAT pathway is implicated in a wide range of diseases, including cancers, autoimmune disorders, and immune deficiencies; thus, it is a major avenue for drug discovery, with several JAK inhibitors now used clinically for various indications.

Other names

JAK-STAT pathwayJAK/STAT signalingJanus kinases and STATsJAK/STAT cascade

Inhibition of JAK kinases blocks cytokine- and growth factor-mediated intracellular signal transduction, reducing STAT activation and downstream gene expression; As a result, immune cell activation, proliferation, and inflammatory gene programs are reduced