The family of Janus kinase (JAK) tyrosine kinases consists of 4 members: JAK1, JAK2, JAK3 and tyrosine kinase 2(TYK2). These intracellular proteins are characterized by an amino-terminal portion of approximately 600 amino acids and two kinase domains, each of about 250 residues, separated by a short hinge region. While the expression of JAK1, JAK2 and TYK2 is ubiquitous, JAK3 is expressed predominantly in hematopoetic cells. JAKs are activated upon high-affinity binding of a variety of cytokines to their multimeric cell-surface receptors. When activated, JAKs can phosphorylate the cytokine receptors, creating docking sites for signaling molecules, especially members of the STAT family...