The Jak/STAT pathway is activated by a large number of cytokines and growth factors. Activators of Jak/STAT signaling generally bind to receptors that lack intrinsic kinase activity and thus utilize intracellular enzymes to initiate downstream signaling. These compounds include type I/II Interferons and the IL-6, IL-10, IL-12, Common gamma Chain, and Common beta Chain families of cytokines. Binding of a cytokine or growth factor to its receptor activates the non-receptor protein tyrosine kinases Janus Kinases (Jaks). Activated Jaks subsequently phosphorylate the receptor and the Signal Transducers and Activators of Transcription (STAT) transcription factors. Activated STAT proteins dissociate from the receptor, dimerize, and translocate to the nucleus where they regulate the expression of target genes.
Signaling through the Jak/STAT pathway is critical for many processes including hematopoiesis, immune cell proliferation and differentiation, and inflammation. This pathway is tightly controlled as dysregulation of Jak/STAT signaling is thought to underlie several disorders including rheumatologic and autoimmune disorders, transplant rejection, and several cancers, such as leukemia, breast cancer, and head and neck cancer.