JAK1 [MD348]

JAK1 is a member of the Janus family of tyrosine kinases (JAK1, JAK2, JAK3, and TYK2), which are activated by ligands binding to a number of associated cytokine receptors and become autophosphorylated and phosphorylate their associated receptors to provide multiple binding sites for signaling proteins. These associated signaling proteins, such as Stats, Shc, insulin receptor substrates, and focal adhesion kinase (FAK), typically contain SH2 or other phospho-tyrosine-binding domains. JAK1 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. Upon ligand binding, JAK1 undergoes tyrosine phosphorylation and catalytic activation in an interdependent manner. Phosphorylation of tyrosine residues at position 1022 and 1023 is believed to function in the activation of catalytic events. 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.