Figure 2.

Hematopoietic cytokine receptor architecture and mechanism of initial signaling. A stylized hematopoietic cytokine receptor is shown, depicting the 1 or 2 cytokine receptor motifs (C, Cys; WS, Trp-Ser-Xaa-Trp-Ser), the transmembrane domain, and the box1 sequence to which JAK kinases bind. Also shown are the 3 major domains of JAK kinases, the FERM domain, which binds to box1, and the kinase JH1 and regulatory JH2 domains. Finally, upon JAK activation, the site of receptor tyrosine phosphorylation is shown, which then serves as a docking site for STATs and adapter proteins (SHC or SHP2).