Figure 2.

Homodimeric cytokine receptor signaling via JAK2. (A) Homodimeric cytokine receptors and conformational changes on activation by ligands. JAK2 binds to boxes 1 and 2 motifs of the cytosolic domains of receptors, via the FERM and SH2 domains, respectively. The region separating the end of the transmembrane domain and the Box 1 is denoted ‘switch region’ and is required for ligand-activation of receptors and JAK2. (B) JAK2 domain structure and the activating mutations in myeloproliferative neoplasms (V617F and insertions and deletions mutating K539) shown as red stars. FERM, SH2, pseudokinase and kinase domains are shown from the NH2- to the COOH-terminus. kinase inhibitors currently in use act on the ATP-binding pocket of the kinase domain and inhibit both mutated and wild type forms of JAK2. EC, extracellular; IC, intracellular; IFN, interferon; JAK, Janus kinase.