 The receptors exist as paired polypeptides, thus exhibiting two intracellular signal-transducing domains.JAKs associate with a proline-rich region in each intracellular domain that is adjacent to the cell membrane and called a box1/box2 region.After the receptor associates with its respective cytokine/ligand, it goes through a conformational change, bringing the two JAKs close enough to phosphorylate each other.