Janus kinases, multidomain proteins consisting of a catalytic or kinase domain associated with pseudokinase, SH2, and FERM domains, associate with cytokine receptors. Upon ligand binding, Janus kinases are activated resulting in their phosphorylation. According to Boggon et al, the Jak3 kinase domain has a typical bilobed structure. Phosphorylation of tyrosine 981 in the activation loop allows interaction with arginine residues in the C-helix of the N lobe, allowing the opening of the binding site cleft. Activation of the kinase results in phosphorylation of the receptor and subsequent activation of the cytosolic family of transcription factor signal transducers and activators of transcription (STATs). Boggon et al also identified other unique structural features of the Jak3 kinase domain, which may mediate interactions of the kinase domain with other regulatory domains.