JAK2 (Janus Kinase 2) belongs to the emerging family of non-receptor Janus tyrosine kinases, which regulate a spectrum of cellular functions downstream of activated cytokine receptors in the lympho-hematopoietic system. Immuno-logical stimuli, such as interferons and cytokines, induce recruitment of Stat transcription factors to cytokine receptor-associated JAK2. JAK2 then phosphorylates proximal Stat factors, which subsequently dimerize, translocate to the nucleus and bind to cis elements upstream of target gene promoters to regulate transcription. The canonical JAK-Stat pathway is integral to maintaining a normal immune system by stimulating proliferation, differentiation, survival, and host resistance to pathogens. Altering JAK-Stat signaling to reduce cytokine induced pro-inflammatory responses represents an attractive target for anti-inflammatory therapies. Within the JAK2 kinase domain, there is a region that has considerable sequence homology to the regulatory region of the insulin receptor. Among a variety of sites, Tyrosines 1007 and 1008 are sites of trans- or autophosphorylation in vivo and in in vitro kinase reactions.
