Members of the Janus family of tyrosine kinases (JAK1, JAK2, JAK3, and Tyk2) are activated by ligands binding to a number of associated cytokine receptors. Upon cytokine receptor activation, JAK proteins become autophosphorylated and phosphorylate their associated receptors to provide multiple binding sites for signaling proteins. JAK2 is autophosphorylated at Tyr1007/1008 in the putative activation loop during cytokine signaling. Tyr221 and 570 have also been shown to be prominent sites for autophosphorylation. In addition, Tyr813 was identified as a site for autophosphorylation critical for the activation of JAK2 by the SH2 domain-containing protein SH2-B β.
