IFN-gamma binding to the receptor complex, induces JAK2 autophosphorylation and activation. Like all protein tyrosine kinases (PTKs) JAK2 activity also depends on the phosphorylation of tandem tyrosine residues within the activation loop that results in the removal of the activation loop from the active site. Multiple phosphorylation sites have been identified in JAK2 (tyrosines 221, 570, 868, 966, 972, 1007 and 1008 ) of which phosphorylation of tyrosine 1007 is essential for kinase activity. Tyrosine 1007 is in the activation loop and phosphorylation allows access of the catalytic loop to the ATP in the ATP binding domain. Of all the predicted phoshorylation sites only tyrosine 1007 is represented in the reaction.